Markus Hartenbach

Combined PET/MRI: Multi-modality Multi-parametric Imaging Is Here: Summary Report of the 4th International Workshop on PET/MR Imaging; February 23-27, 2015, Tübingen, Germany.

This paper summarises key themes and discussions from the 4th international workshop dedicated to the advancement of the technical, scientific and clinical applications of combined positron emission tomography (PET)/magnetic resonance imaging (MRI) systems that was held in Tübingen, Germany, from February 23 to 27, 2015. Specifically, we summarise the three days of invited presentations from active researchers in this and associated fields augmented by round table discussions and dialogue boards with specific topics. These include the use of PET/MRI in cardiovascular disease, paediatrics, oncology, neurology and multi-parametric imaging, the latter of which was suggested as a key promoting factor for the wider adoption of integrated PET/MRI. Discussions throughout the workshop and a poll taken on the final day demonstrated that attendees felt more strongly that PET/MRI has further advanced in both technical versatility and acceptance by clinical and research-driven users from the status quo of last year. Still, with only minimal evidence of progress made in exploiting the true complementary nature of the PET and MRI-based information, PET/MRI is still yet to achieve its potential. In that regard, the conclusion of last year’s meeting “the real work has just started” still holds true.

Combined PET/MR: Where Are We Now? Summary Report of the Second International Workshop on PET/MR Imaging April 8–12, 2013, Tubingen, Germany

This workshop was held a year after the initial positron emission tomography/magnetic resonance (PET/MR) workshop in Tübingen, which was recently reported in this journal. The discussions at the 2013 workshop, however, differed substantially from those of the initial workshop, attesting to the progress of combined PET/MR as an innovative imaging modality. Discussions were focused on the search for truly novel, unique clinical and research applications as well as technical issues such as reliable and accurate approaches for attenuation and scatter correction of PET emission data. The workshop provided hands-on experience with PET and MR imaging. In addition, structured and moderated open discussion sessions, including six dialogue boards and two roundtable discussions, provided input from current and future PET/MR imaging users. This summary provides a snapshot of the current achievements and challenges for PET/MR.

Combined PET/MRI Improves Diagnostic Accuracy in Patients with Prostate Cancer: A Prospective Diagnostic Trial

Purpose: The pretherapeutic assessment of prostate cancer is challenging and still holds the risk of over- or undertreatment. This prospective trial investigates positron emission tomography (PET) with [18F]fluoroethylcholine (FEC) combined with endorectal magnetic resonance imaging (MRI) for the assessment of primary prostate cancer. Experimental design: Patients with prostate cancer based on needle biopsy findings, scheduled for radical prostatectomy, were assessed by FEC-PET and MRI in identical positioning. After prostatectomy, imaging results were compared with histologic whole-mount sections, and the PET/MRI lesion-based semiquantitative FEC uptake was compared with biopsy Gleason scores and postoperative histology. Results: PET/MRI showed a patient-based sensitivity of 95% (36/38; 95% confidence interval (CI), 82%–99%). The analysis of 128 prostate lesions demonstrated a sensitivity/specificity/positive predictive value/negative predictive value/accuracy of 67%/35%/59%/44%/54% (P = 0.8295) for MRI and 85%/45%/68%/69%/68% (P = 0.0021) for PET, which increased to 84%/80%/85%/78%/82% (P < 0.0001) by combined FEC-PET/MRI in lesions >5 mm (n = 98). For lesions in patients with Gleason >6 tumors (n = 43), MRI and PET achieved 73%/31%/71%/33%/60% (P = 1.0000) and 90%/62%/84%/73%/81% (P = 0.0010), which were improved to 87%/92%/96%/75%/88% (P < 0.0001) by combined PET/MRI. Applying semiquantitative PET analysis, carcinomas with Gleason scores >6 were distinguished from those with Gleason ≤6 with a specificity of 90% and a positive predictive value of 83% (P = 0.0011; needle biopsy 71%/60%, P = 0.1071). Conclusions: In a prospective diagnostic trial setting, combined FEC-PET/MRI achieved very high sensitivity in the detection of the dominant malignant lesion of the prostate, and markedly improved upon PET or MRI alone. Noninvasive Gleason score assessment was more precise than needle biopsy in this patient cohort. Hence, FEC-PET/MRI merits further investigation in trials of randomized, multiarm design. Clin Cancer Res; 20(12); 3244–53. ©2014 AACR.

Evaluation of fatty acid synthase in prostate cancer recurrence: SUV of [(11) C]acetate PET as a prognostic marker.

High levels of fatty acid synthase have shown to correlate with the aggressiveness of prostate cancer. As [11C]acetate exhibits a close correlation with the level of fatty acid synthase, we aimed to assess whether the SUV in [11C]acetate PET serves as a suitable prognostic marker in patients with recurrent prostate cancer.

Evaluating Treatment Response of Radioembolization in Intermediate-Stage Hepatocellular Carcinoma Patients Using 18F-Fluoroethylcholine PET/CT

The aim of this study was to evaluate 18F-fluoroethylcholine PET/CT as a metabolic imaging technique for the assessment of treatment response to 90Y radioembolization in patients with locally advanced hepatocellular carcinoma (HCC). Methods: Thirty-four HCC patients undergoing 78 18F-fluoroethylcholine PET/CT scans were identified for this study. Patients with initial or follow-up metastastic disease (n = 9) were excluded at the time point of the metastatic occurrence as well as patients with negative α-fetoprotein (AFP; n = 1), resulting in 24 patients and 57 scans that were eligible. All patients were scheduled for radioembolization and underwent 1 pretherapeutic and at least 1 posttherapeutic 18F-fluoroethylcholine PET/CT scan. Volume-of-interest analysis and volume-of-interest subtractions were performed. Maximum, mean, and peak standardized uptake value (SUV) analysis was performed, and the total intrahepatic 18F-fluoroethylcholine positive tumor volume (FEC-PTV) and tumor-to-background ratio were assessed. Statistical analysis was performed using a decreasing AFP of at least 20% as a standard of reference for therapy response including receiver-operating-characteristic analyses as well as descriptive and correlation analyses and multiple logistic regression. Results: Fourteen follow-up examinations were categorized as responder and 19 follow-up examinations as nonresponder. Absolute AFP values did not correlate with SUV parameters (P = 0.055). In receiver-operating-characteristic analyses, the initial mean SUV, Δmaximum SUV, and Δtumor-to-background ratio demonstrated the highest area under the curve, 0.84 (P = 0.009), 0.83 (P = 0.011), and 0.83 (P = 0.012), respectively, resulting in a positive prediction of 82%, 83%, and 91% at the respective cutoff points. When multiple logistic regression analysis was applied, this resulted in an area under the curve of 0.90 (P = 0.001), with a positive prediction of 94% and a sensitivity of 94%. The FEC-PTV did not reach significance in the presented dataset. Conclusion: 18F-fluoroethylcholine PET/CT demonstrates a high potential for follow-up assessment in the context of radioembolization in patients with locally advanced, but nonmetastatic, HCC and initially elevated AFP, possibly enabling early therapy monitoring independent of morphology.

Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE): Proposed miTNM Classification for the Interpretation of PSMA-Ligand PET/CT

Prostate-specific membrane antigen (PSMA)–ligand PET imaging provides unprecedented accuracy for whole-body staging of prostate cancer. As PSMA-ligand PET/CT is increasingly adopted in clinical trials and routine practice worldwide, a unified language for image reporting is urgently needed. We propose a molecular imaging TNM system (miTNM, version 1.0) as a standardized reporting framework for PSMA-ligand PET/CT or PET/MRI. miTNM is designed to organize findings in comprehensible categories to promote the exchange of information among physicians and institutions. Additionally, flowcharts integrating findings of PSMA-ligand PET and morphologic imaging have been designed to guide image interpretation. Specific applications, such as assessment of prognosis or impact on management, should be evaluated in future trials. miTNM is a living framework that evolves with clinical experience and scientific data.

Does Delayed-Time-Point Imaging Improve 18F-FDG-PET in Patients With MALT Lymphoma?: Observations in a Series of 13 Patients.

Purpose To determine whether in patients with extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue lymphoma (MALT), delayed–time-point 2-18F-fluoro-2-deoxy-d-glucose-positron emission tomography (18F-FDG-PET) performs better than standard–time-point 18F-FDG-PET. Materials and Methods Patients with untreated histologically verified MALT lymphoma, who were undergoing pretherapeutic 18F-FDG-PET/computed tomography (CT) and consecutive 18F-FDG-PET/magnetic resonance imaging (MRI), using a single 18F-FDG injection, in the course of a larger-scale prospective trial, were included. Region-based sensitivity and specificity, and patient-based sensitivity of the respective 18F-FDG-PET scans at time points 1 (45–60 minutes after tracer injection, TP1) and 2 (100–150 minutes after tracer injection, TP2), relative to the reference standard, were calculated. Lesion-to-liver and lesion-to-blood SUVmax (maximum standardized uptake values) ratios were also assessed. Results 18F-FDG-PET at TP1 was true positive in 15 o f 23 involved regions, and 18F-FDG-PET at TP2 was true-positive in 20 of 23 involved regions; no false-positive regions were noted. Accordingly, region-based sensitivities and specificities were 65.2% (confidence interval [CI], 45.73%–84.67%) and 100% (CI, 100%-100%) for 18F-FDG-PET at TP1; and 87.0% (CI, 73.26%–100%) and 100% (CI, 100%-100%) for 18F-FDG-PET at TP2, respectively. FDG-PET at TP1 detected lymphoma in at least one nodal or extranodal region in 7 of 13 patients, and 18F-FDG-PET at TP2 in 10 of 13 patients; accordingly, patient-based sensitivity was 53.8% (CI, 26.7%–80.9%) for 18F-FDG-PET at TP1, and 76.9% (CI, 54.0%–99.8%) for 18F-FDG-PET at TP2. Lesion-to-liver and lesion-to-blood maximum standardized uptake value ratios were significantly lower at TP1 (ratios, 1.05 ± 0.40 and 1.52 ± 0.62) than at TP2 (ratios, 1.67 ± 0.74 and 2.56 ± 1.10; P = 0.003 and P = 0.001). Conclusions Delayed–time-point imaging may improve 18F-FDG-PET in MALT lymphoma.

Task-relevant brain networks identified with simultaneous PET/MR imaging of metabolism and connectivity

Except for task-specific functional MRI, the vast majority of imaging studies assessed human brain function at resting conditions. However, tracking task-specific neuronal activity yields important insight how the brain responds to stimulation. We specifically investigated changes in glucose metabolism, functional connectivity and white matter microstructure during task performance using several recent methodological advancements. Opening the eyes and right finger tapping had elicited an increased glucose metabolism in primary visual and motor cortices, respectively. Furthermore, a decreased metabolism was observed in the regions of the default mode network, which allowed absolute quantification of commonly described deactivations during cognitive tasks. These brain regions showed widespread task-specific changes in functional connectivity, which stretched beyond their primary resting-state networks and presumably reflected the level of recruitment of certain brain regions for each task. Finally, the corresponding white matter fiber pathways exhibited changes in axial and radial diffusivity during the tasks, which were regionally distinctive for certain tract groups. These results highlight that even simple task performance leads to substantial changes of entire brain networks. Exploiting the complementary nature of the different imaging modalities may reveal novel insights how the brain processes external stimuli and which networks are involved in certain tasks.

Reproducibility of MRI Dixon-based attenuation correction in combined PET/MR with applications for lean body mass estimation

The aim of this study was to assess the reproducibility of standard, Dixon-based attenuation correction (MR-AC) in PET/MR imaging. A further aim was to estimate a patient-specific lean body mass (LBM) from these MR-AC data. Methods: Ten subjects were positioned in a fully integrated PET/MR system, and 3 consecutive multibed acquisitions of the standard MR-AC image data were acquired. For each subject and MR-AC map, the following compartmental volumes were calculated: total body, soft tissue (ST), fat, lung, and intermediate tissue (IT). Intrasubject differences in the total body and subcompartmental volumes (ST, fat, lung, and IT) were assessed by means of coefficients of variation (CVs) calculated across the 3 consecutive measurements and, again, across these measurements but excluding those affected by major artifacts. All subjects underwent a body composition measurement using air displacement plethysmography (ADP) that was used to calculate a reference LBMADP. A second LBM estimate was derived from available MR-AC data using a formula incorporating the respective tissue volumes and densities as well as the subject-specific body weights. A third LBM estimate was obtained from a sex-specific formula (LBMFormula). Pearson correlation was calculated for LBMADP, LBMMR-AC, and LBMFormula. Further, linear regression analysis was performed on LBMMR-AC and LBMADP. Results: The mean CV for all 30 scans was 2.1 ± 1.9% (TB). When missing tissue artifacts were excluded, the CV was reduced to 0.3 ± 0.2%. The mean CVs for the subcompartments before and after exclusion of artifacts were 0.9 ± 1.1% and 0.7 ± 0.7% for the ST, 2.9 ± 4.1% and 1.3 ± 1.0% for fat, and 3.6 ± 3.9% and 1.3 ± 0.7% for the IT, respectively. Correlation was highest for LBMMR-AC and LBMADP (r = 0.99). Linear regression of data excluding artifacts resulted in a scaling factor of 1.06 for LBMMR-AC. Conclusion: LBMMR-AC is shown to correlate well with standard LBM measurements and thus offers routine LBM-based SUV quantification in PET/MR. However, MR-AC images must be controlled for systematic artifacts, including missing tissue and tissue swaps. Efforts to minimize these artifacts could help improve the reproducibility of MR-AC.

Reduced task durations in functional PET imaging with [18F]FDG approaching that of functional MRI

Introduction: The brains energy budget can be non‐invasively assessed with different imaging modalities such as functional MRI (fMRI) and PET (fPET), which are sensitive to oxygen and glucose demands, respectively. The introduction of hybrid PET/MRI systems further enables the simultaneous acquisition of these parameters. Although a recently developed method offers the quantification of task‐specific changes in glucose metabolism (CMRGlu) in a single measurement, direct comparison of the two imaging modalities is still difficult because of the different temporal resolutions. Thus, we optimized the protocol and systematically assessed shortened task durations of fPET to approach that of fMRI. Methods: Twenty healthy subjects (9 male) underwent one measurement on a hybrid PET/MRI scanner. During the scan, tasks were completed in four blocks for fMRI (4×30s blocks) and fPET: participants tapped the fingers of their right hand repeatedly to the thumb while watching videos of landscapes. For fPET, subjects were randomly assigned to groups of n=5 with varying task durations of 10, 5, 2 and 1min, where task durations were kept constant within a measurement. The radiolabeled glucose analogue [18F]FDG was administered as 20% bolus plus constant infusion. The bolus increases the signal‐to‐noise ratio and leaves sufficient activity to detect task‐related effects but poses additional challenges due to a discontinuity in the tracer uptake. First, three approaches to remove task effects from the baseline term were evaluated: (1) multimodal, based on the individual fMRI analysis, (2) atlas‐based by removing presumably activated regions and (3) model‐based by fitting the baseline with exponential functions. Second, we investigated the need to capture the arterial input function peak with automatic blood sampling for the quantification of CMRGlu. We finally compared the task‐specific activation obtained from fPET and fMRI qualitatively and statistically. Results: CMRGlu quantified only with manual arterial samples showed a strong correlation to that obtained with automatic sampling (r=0.9996). The multimodal baseline definition was superior to the other tested approaches in terms of residuals (p<0.001). Significant task‐specific changes in CMRGlu were found in the primary visual and motor cortices (tM1=18.7 and tV1=18.3). Significant changes of fMRI activation were found in the same areas (tM1=16.0 and tV1=17.6) but additionally in the supplementary motor area, ipsilateral motor cortex and secondary visual cortex. Post‐hoc t‐tests showed strongest effects for task durations of 5 and 2min (all p<0.05 FWE corrected), whereas 1min exhibited pronounced unspecific activation. Percent signal change (PSC) was higher for CMRGlu (˜18%–27%) compared to fMRI (˜2%). No significant association between PSC of task‐specific CMRGlu and fMRI was found (r=0.26). Conclusion: Using a bolus plus constant infusion protocol, the necessary task duration for reliable quantification of task‐specific CMRGlu could be reduced to 5 and 2min, therefore, approaching that of fMRI. Important for valid quantification is a correct baseline definition, which was ideal when task‐relevant voxels were determined with fMRI. The absence of a correlation and the different activation pattern between fPET and fMRI suggest that glucose metabolism and oxygen demand capture complementary aspects of energy demands. HIGHLIGHTSQuantification of task‐specific CMRGlu with 20% bolus plus constant infusion.Functional PET task durations down to 1min were evaluated.Active primary regions overlap between BOLD and CMRGlu.No significant correlation between BOLD and CMRGlu.