Development of a Hybrid-Imaging-Based Prognostic Index for Metastasized-Melanoma Patients in Whole-Body 18F-FDG PET/CT and PET/MRI Data.

Besides tremendous treatment success in advanced melanoma patients, the rapid development of oncologic treatment options comes with increasingly high costs and can cause severe life-threatening side effects. For this purpose, predictive baseline biomarkers are becoming increasingly important for risk stratification and personalized treatment planning. Thus, the aim of this pilot study was the development of a prognostic tool for the risk stratification of the treatment response and mortality based on PET/MRI and PET/CT, including a convolutional neural network (CNN) for metastasized-melanoma patients before systemic-treatment initiation. The evaluation was based on 37 patients (19 f, 62 ± 13 y/o) with unresectable metastasized melanomas who underwent whole-body 18F-FDG PET/MRI and PET/CT scans on the same day before the initiation of therapy with checkpoint inhibitors and/or BRAF/MEK inhibitors. The overall survival (OS), therapy response, metastatically involved organs, number of lesions, total lesion glycolysis, total metabolic tumor volume (TMTV), peak standardized uptake value (SULpeak), diameter (Dmlesion) and mean apparent diffusion coefficient (ADCmean) were assessed. For each marker, a Kaplan−Meier analysis and the statistical significance (Wilcoxon test, paired t-test and Bonferroni correction) were assessed. Patients were divided into high- and low-risk groups depending on the OS and treatment response. The CNN segmentation and prediction utilized multimodality imaging data for a complementary in-depth risk analysis per patient. The following parameters correlated with longer OS: a TMTV < 50 mL; no metastases in the brain, bone, liver, spleen or pleura; ≤4 affected organ regions; no metastases; a Dmlesion > 37 mm or SULpeak < 1.3; a range of the ADCmean < 600 mm2/s. However, none of the parameters correlated significantly with the stratification of the patients into the high- or low-risk groups. For the CNN, the sensitivity, specificity, PPV and accuracy were 92%, 96%, 92% and 95%, respectively. Imaging biomarkers such as the metastatic involvement of specific organs, a high tumor burden, the presence of at least one large lesion or a high range of intermetastatic diffusivity were negative predictors for the OS, but the identification of high-risk patients was not feasible with the handcrafted parameters. In contrast, the proposed CNN supplied risk stratification with high specificity and sensitivity.

Is there a link between very early changes of primary and secondary lymphoid organs in 18F-FDG-PET/MRI and treatment response to checkpoint inhibitor therapy?

Response assessment or prediction to checkpoint inhibitor therapy (CIT) is an unsolved problem in current routine diagnostics of patients with melanoma. Here, we evaluated very early changes of primary and secondary lymphoid organs under CIT in multiparametric [18F]-labeled fluorodeoxyglucose-positron emission tomography (18F-FDG-PET)/MRI as possible predictors of treatment response and investigated their correlation with baseline blood immune biomarkers. Between October 2014 and November 2017, 17 patients with unresectable melanoma (8 females; 65±11 years) undergoing CIT were prospectively evaluated using whole-body 18F-FDG-PET/MRI before CIT start (t0), 2 weeks (t1) and 3 months after CIT initiation (t2). At each time point, the volume, the 18F-FDG-uptake and the mean apparent diffusion coefficient (ADC) of the spleen as well as the 18F-FDG uptake of the bone marrow were assessed. Relative lymphocyte count (RLC), relative eosinophil count (REC) and neutrophil-lymphocyte ratio (NLR) were assessed at baseline. Response Evaluation Criteria in Solid Tumours modified for immune-based therapeutics (iRECIST) and decisions from an interdisciplinary tumor board were used for treatment response evaluation at t2 iRECIST was compared with PET response criteria in solid tumors for image-based response evaluation at different time points. Comparative analysis was conducted with Mann-Whitney U test with false discovery rate correction for multiple testing and correlation coefficients were computed. In lymphoid organs, significant differences (p<0.05) between responders (9/17) and non-responders were found for the 18F-FDG-uptake in the spleen at t1 and the increase of the uptake t1-t0 (responders/non-responders: standardized uptake value lean body mass 1.19/0.93; +49%/-1%). The best correlation coefficients to baseline biomarkers were found for the 18F-FDG-uptake in the spleen at t1: NLR, r=-0.46; RLC, r=0.43; REC, r=0.58 (p<0.05), respectively. Compared with the non-responder group, the responder group showed marked increases also in the volume of the spleen (+22%/+10%), the 18F-FDG-uptake of bone marrow (+31%/-9%) at t1 and the ADCmean at t2 (+46%/+15%) compared with t0, however, not reaching significance. Our findings indicate that an effective systemic immune response in patients undergoing CIT can be detected as a significantly increased spleen activity in 18F-FDG-PET as early as 2 weeks after treatment initiation. TRIAL REGISTRATION NUMBER: NCT03132090, DRKS00013925.

Comprehensive metabolic and morphologic disease characterization in systemic sclerosis: initial results using combined positron emission tomography and magnetic resonance imaging.

BACKGROUND: The aim of this study was to evaluate the role of metabolic and morphologic parameters derived from simultaneous hybrid PET/MRI in correlation to clinical criteria for an image-based characterization of musculoskeletal, esophagus and lymph node involvement in systemic sclerosis (SSc). METHODS: Between November 2013 and May 2015, simultaneous whole-body hybrid PET/MRI was performed in 13 prospectively recruited patients with SSc. A mean dose of 241.3 MBq 2-deoxy-2-[18F]fluoro-D-glucose (FDG) was injected. SUVmean and SUVmax values were measured in the spinal bone marrow, spleen, joints, muscles, fasciae, mediastinal lymph nodes and esophagus. MRI abnormalities were scored as 0 (absent), 1 (moderate) and 2 (marked). In addition, organ and skin involvement were graded with clinical sum score (CSS) and modified Rodnan skin score (mRSS), respectively. RESULTS: Results indicate positive correlations between mRSS and fascial FDG-uptake values (fascia summed SUVmax ρ=0.67; fascia summed SUVmean ρ=0.66) that performed better than the MRI sum score (ρ=0.50). Fascial FDG-uptake is also useful in the differentiation between diffuse and limited SSc. Additionally, FDG-PET detected patients with active mediastinal lymphadenopathy and MRI proved to be useful for the delineation of esophagus involvement. CONCLUSIONS: Fascial FDG-uptake has a strong correlation with mRSS and can discriminate between limited and diffuse SSc. These results and the detection of active lymphadenopathy and esophagus involvement can identify patients with advanced scleroderma. Combined PET/MRI therefore provides complementary information on the complex pathophysiology and may integrate several imaging procedures in one.

Spatial-temporal perfusion patterns of the human liver assessed by pseudo-continuous arterial spin labeling MRI.

PURPOSE: To investigate the capabilities of a modern pseudo-continuous arterial spin labeling (PCASL) technique for non-invasive assessment of the temporal and spatial distribution of the liver perfusion in healthy volunteers on a clinical MR system at 3T. MATERIALS AND METHODS: A 2D-PCASL multi-slice echo planar imaging sequence was adapted to the specific conditions in liver: a) labeling by PCASL was optimized to the flow characteristics in the portal vein, b) background suppression was applied for reduction of motion related artifacts, c) post labeling delays (PLDs) were varied over a large range (0.7-3.5s) in order to get better insight in the temporal and spatial distribution of tagged blood in the liver, and d) a special timed-breathing protocol was used allowing for recording of 16 to 18 label-control image pairs and a reference M0 image for each of 4 to 6 slices within approx. 5min for one PLD. RESULTS: Measurements with multiple PLDs showed dominating perfusion signal in macroscopic blood vessels for PLDs up to 1.5 s, whereas pure liver parenchyma revealed maximum perfusion signal for a PLD of approx. 2 s, and detectable signal up to PLDs of 3.5 s. Data fitting to a perfusion model for liver provided a mean global perfusion of 153±15ml/100g/min and a mean transit time of 1938±332ms in liver parenchyma. Measurements with a single PLD of 2 s demonstrated that portal-venous and arterial perfusion components can be measured separately by two measurements with two different positions of the labeling plane (one for labeling of the global hepatopetal blood flow and one for selective labeling of the portal blood flow only). Relative contribution of blood from the hepatic artery to the global liver perfusion, the hepatic perfusion index (HPI), amounted to approx. 23%. CONCLUSION: Modern and adapted protocols for assessment of liver perfusion by PCASL have the potential to provide perfusion and blood transit time maps in reasonable acquisition time.

Computed diffusion weighted imaging (cDWI) and voxelwise-computed diffusion weighted imaging (vcDWI) for oncologic liver imaging: A pilot study.

OBJECTIVE: Aim of the study was to evaluate the influence of the selection of measured b-values on the precision of cDWI in the upper abdomen as well as on the lesion contrast of PET-positive liver metastases in cDWI and vcDWI. METHODS: We performed a retrospective analysis of 10 patients (4 m, 63.5 ±â€¯12.9 y/o) with PET-positive liver metastases examined in 3 T-PET/MRI with b = 100,600,800,1000 and 1500s/mm2. cDWI (cb1000/cb1500) and vcDWI were computed based on following combinations: i) b = 100/600 s/mm2, ii) b = 100/800 s/mm2, iii) b = 100/1000s/mm2, iv) b = 100/600/1000s/mm2 v) all measured b-values. Mean signal intensity (SI) and standard deviation (SD) in the liver, spleen, kidney, bone marrow and in liver lesions were acquired. The coefficient of variation (CV = SD/SI), the differences of SI between measured and calculated high b-value images and the lesion contrast (SI lesion/liver) were computed. RESULTS: With increasing upper measured b-values, the CV in cDWI and vcDWI decreased (CV in the liver in cb1500: 0.42 with b100/600 s/mm2 and 0.28 with b100/b1000s/mm2) while the differences of measured and calculated b-value images decreased (in the liver in cb1500: 30.7% with b = 100/600 s/mm2, 19.7% with b100/b1000s/mm2). In diffusion-restricted lesions, lesion contrast was at least 1.6 in cb1000 and 1.4 in cb1500, respectively, with an upper measured b-value of b = 800 s/mm2 and 2.1 for vcDWI with an upper measured b-value of b = 1000s/mm2. Overall, the lesion contrast was superior in cb1500 and vcDWI compared to cb1000 (15% and 11%, respectively). CONCLUSION: Measuring higher upper b-values seems to lead to more precise computed high b-value images and a decrease of CV. vcDWI provides a comparable lesion contrast to b = 1500s/mm2 and offers additionally the reduction of T2 shine-through effects. For vcDWI, measuring b = 1000s/mm2 as upper b-value seems to be necessary to guarantee good lesion visibility in the liver based on our preliminary results.

Fast non-enhanced abdominal examination protocols in PET/MRI for patients with neuroendocrine tumors (NET): comparison to multiphase contrast-enhanced PET/CT.

PURPOSE: To evaluate fast non-enhanced protocols for abdominal PET/MRI in comparison to contrast-enhanced PET/CT with somatostatin receptor (SSR)-specific radiotracers regarding effectiveness of lesion detection in NET patients. METHODS: This was a retrospective analysis of 29 patients (12 male, 57 ± 13 years) who underwent PET/CT and subsequently PET/MRI at the same day. Two readers evaluated independently four PET/MRI setups: (I) PET + T2 Half Fourier Acquisition Single Shot Turbo Spin Echo (T2 HASTE), (II) PET + T2 HASTE + T2-weighted spin-echo sequence (T2 TSE), III) PET + T2 HASTE + Diffusion Weighted Imaging (DWI) and (IV) PET + T2 HASTE + T2 TSE + DWI. A consensus reading of PET/MRI and PET/CT including follow-up examinations served as the reference standard for lesion-based analysis. Lesion sizes were assessed. RESULTS: Setup IV provided comparable overall detection rates as PET/CT in both readers: PET/MRI 91.5%/92.9% versus 89.7% in PET/CT. In liver and bone lesions (mean diameter: 1.9 and 1.5 cm), PET/MRI was equal or superior to PET/CT: 98%/98% versus 85% in PET/CT; 100%/95% versus 100% in PET/CT, but inferior in pancreatic lesions, small bowel lesions and lymph node metastases (mean diameter: 1.3, 0.5 and 1.8 cm). CONCLUSION: A non-enhanced MR protocol comprising T2 HASTE, T2 TSE and DWI for SSR-PET/MRI seems to provide comparable effectiveness in lesions detection as multiphase contrast-enhanced PET/CT. It might, therefore, serve as valid alternative, e.g., for follow-up examinations in patients with unresectable NET and kidney failure.

Assessment of image quality of a radiotherapy-specific hardware solution for PET/MRI in head and neck cancer patients.

BACKGROUND AND PURPOSE: Functional PET/MRI has great potential to improve radiotherapy planning (RTP). However, data integration requires imaging with radiotherapy-specific patient positioning. Here, we investigated the feasibility and image quality of radiotherapy-customized PET/MRI in head-and-neck cancer (HNC) patients using a dedicated hardware setup. MATERIAL AND METHODS: Ten HNC patients were examined with simultaneous PET/MRI before treatment, with radiotherapy and diagnostic scan setup, respectively. We tested feasibility of radiotherapy-specific patient positioning and compared the image quality between both setups by pairwise image analysis of 18F-FDG-PET, T1/T2-weighted and diffusion-weighted MRI. For image quality assessment, similarity measures including average symmetric surface distance (ASSD) of PET and MR-based tumor contours, MR signal-to-noise ratio (SNR) and mean apparent diffusion coefficient (ADC) value were used. RESULTS: PET/MRI in radiotherapy position was feasible - all patients were successfully examined. ASSD (median/range) of PET and MR contours was 0.6 (0.4-1.2) and 0.9 (0.5-1.3) mm, respectively. For T2-weighted MRI, a reduced SNR of -26.2% (-39.0--11.7) was observed with radiotherapy setup. No significant difference in mean ADC was found. CONCLUSIONS: Simultaneous PET/MRI in HNC patients using radiotherapy positioning aids is clinically feasible. Though SNR was reduced, the image quality obtained with a radiotherapy setup meets RTP requirements and the data can thus be used for personalized RTP.

Voxel-wise correlation of functional imaging parameters in HNSCC patients receiving PET/MRI in an irradiation setup.

PURPOSE: The purpose of this study was to demonstrate the feasibility of voxel-wise multiparametric characterization of head and neck squamous cell carcinomas (HNSCC) using hybrid multiparametric magnetic resonance imaging and positron emission tomography with [18F]-fluorodesoxyglucose (FDG-PET/MRI) in a radiation treatment planning setup. METHODS: Ten patients with locally advanced HNSCC were examined with a combined FDG-PET/MRI in an irradiation planning setup. The multiparametric imaging protocol consisted of FDG-PET, T2-weighted transverse short tau inversion recovery sequence (STIR) and diffusion-weighted MRI (DWI). Primary tumours were manually segmented and quantitative imaging parameters were extracted. PET standardized uptake values (SUV) and DWI apparent diffusion coefficients (ADC) were correlated on a voxel-wise level. RESULTS: Images acquired in this specialised radiotherapy planning setup achieved good diagnostic quality. Median tumour volume was 4.9 [1.1-42.1] ml. Mean PET SUV and ADC of the primary tumours were 5 ± 2.5 and 1.2 ± 0.3 10-3 mm2/s, respectively. In voxel-wise correlation between ADC values and corresponding FDG SUV of the tumours, a significant negative correlation was observed (r = -0.31 ± 0.27, p < 0.05). CONCLUSION: Multiparametric voxel-wise characterization of HNSCC is feasible using combined PET/MRI in a radiation planning setup. This technique may provide novel insights into tumour biology with regard to radiation therapy in the future.

Simultaneous multislice diffusion-weighted imaging in whole-body positron emission tomography/magnetic resonance imaging for multiparametric examination in oncological patients.

OBJECTIVES: The aim of this study was to compare the diagnostic performance of simultaneous multislice diffusion-weighted imaging (DWI-SMS) with that of standard DWI (DWI-STD) in whole-body 3-T PET/MRI examination protocols in oncological patients. METHODS: In a phantom study, we evaluated the apparent diffusion coefficients (ADC) from the two techniques. In ten volunteers, we assessed ADC values in different organs. In 20 oncological patients, we evaluated subjective image quality (Likert scale, 5 indicating excellent) and artefacts in different body regions. We also rated the conspicuity and acquired the ADC values of PET-positive tumorous lesions. RESULTS: The scan time for the whole-body DWI-SMS examinations was 40% shorter than the scan time for the DWI-STD examinations (84 s vs. 140 s per table position). The phantom and volunteer studies showed lower ADC values from DWI-SMS in the liver and muscle (psoas muscle 1.4 vs. 1.3). In patients, DWI-SMS provided poorer subjective image quality in the thoracoabdominal region (3.0 vs. 3.8, p = 0.02) and overall more artefacts (138 vs. 105). No significant differences regarding conspicuity and ADC values of lesions were found. CONCLUSIONS: DWI-SMS seems to provide reliable conspicuity and ADC values of tumorous lesions similar to those provided by DWI-STD. Therefore, although providing poorer image quality in certain regions, DWI-SMS can clearly reduce PET/MRI scan times in oncological patients. KEY POINTS: • DWI-SMS can reduce PET/MRI scan times in oncological patients. • DWI-SMS provides reliable ADC values and good lesion conspicuity similar to those provided by DWI-STD. • DWI-SMS may provide poorer image quality in regions with low signal.

Imaging giant cell arteritis and Aortitis in contrast enhanced 18F-FDG PET/CT: Which imaging score correlates best with laboratory inflammation markers?

PURPOSE: To define the most appropriate imaging parameters in combined Fluorodeoxyglucose (FDG) PET/CT reflecting the inflammatory burden in large vessel vasculitis. METHODS: Two readers retrospectively graded disease extent and activity in 17 LVV patients using visual and quantitative scores in FDG PET and contrast enhanced CT. Visual PET scores were assessed corresponding to FDG-uptake vs. liver uptake (score 0-3). CT visual scoring referred to the affected vessel extent (score 1-5). Quantitative PET scores relied on normalized SUV ratios. For quantitative CT evaluation vessel wall thickness was correlated with FDG- uptake. Imaging scores were correlated with Erythrocyte Sedimentation Rate (ESR) and C-reactive protein (CRP). Intraclass correlation coefficients (ICC) were measured for interreader reliability. RESULTS: Visual PET scores showed stronger correlation with CRP (ρ 0.640, 0.541 for reader I and II, respectively) than with ESR levels (ρ 0.477, 0.447). Quantitative PET showed strongest correlation with CRP using liver as reference tissue. Visual CT scores did neither correlate with ESR nor with CRP levels (ESR: ρ 0.085, 0.294 with p 0.743, 0.252; CRP: ρ 0.322, 0.395 with p 0.208, 0.116). Quantitative CT evaluation correlated with ESR levels in one reader (ρ 0.505, -0.026), however no correlation between quantitative CT measures and quantitative PET scores was found. Best ICC between readers was 0.994 for highest SUVavg vessel/highest SUVavg liver. CONCLUSIONS: Visual and quantitative PET scores were superior to CT scores with best ICC and strongest correlations between quantitative PET score and inflammation markers especially when using vessel to liver ratios.

18F-FDG-PET detects complete response to PD1-therapy in melanoma patients two weeks after therapy start.

PURPOSE: The aim of the study was to evaluate if 18F-FDG-PET has the potential to detect complete responders to PD1-therapy in patients with unresectable metastasized melanoma two weeks after therapy initiation. METHODS: Between September 2014 and May 2016, ten patients (four females; 65 ± 12 y) received a whole-body 18F-FDG-PET/MRI examination at three time points: Before therapy start (t0, base-line), two weeks (t1, study examination) and three months after treatment initiation (t2, reference standard). Therapy response was assessed with PET response criteria in solid tumors (PERCIST). Time to progression and overall survival (OS) were obtained for all patients. RESULTS: Three patients with partial metabolic response in PET at t1 turned out to have complete response at t2. No tumor relapse was observed in those patients so far (observation period: 265, 511 and 728 days, respectively). At t2, progressive metabolic disease (PMD) was seen in six patients from whom four showed PMD and two showed stable metabolic disease (SMD) at t1. OS in patients with PMD at t2 varied between 148 and 814 days. SMD at both t1 and t2 was seen in one patient, tumor progress was observed after 308 days. CONCLUSION: Our study indicates that whole-body 18F-FDG-PET might be able to reliably identify complete responders to PD1-therapy as early as two weeks after therapy initiation in stage IV melanoma patients. This might help to shorten therapy regimes and avoid unnecessary side effects in the future.

Scan time reduction in diffusion-weighted imaging of the pancreas using a simultaneous multislice technique with different acceleration factors: How fast can we go?

OBJECTIVES: To investigate the feasibility of simultaneous multislice-accelerated diffusion-weighted imaging (sms-DWI) of the pancreas with different acceleration factors and its influence on image quality, acquisition time and apparent diffusion coefficients (ADCs) in comparison to conventional sequences. METHODS: DWI of the pancreas was performed at 1.5T in ten healthy volunteers and 20 patients with sms-accelerated echo-planar DWI using two different sms-acceleration factors of 2 and 3 (sms2/3-DWI). These DWI sequences were compared to conventional DWI (c-DWI) in terms of image quality parameters (5-point Likert scale) and ADC measurements. RESULTS: c-DWI and sms2-DWI offered equivalently high overall image quality (4 [1; 5]) with scan time reduction to one-third (c-DWI: 173 s, sms2-DWI: 56 s). Sms3-DWI showed significantly poorer overall image quality (3 [1; 5]; p < 0.0001). ADC values were significantly lower in sms3-DWI compared to c-DWI in the pancreatic body and tail (body: c-DWI 1.4 x 10-3 mm2/s, sms3-DWI 1.0 x 10-3 mm2/s, p = 0.028; tail: c-DWI 1.3 x 10-3 mm2/s and sms3-DWI 1.0 x 10-3 mm2/s, p = 0.014). CONCLUSIONS: Accelerated multislice DWI of the pancreas offers high image quality with a substantial reduction of acquisition time. Lower ADC values in multislice DWI should be considered in diagnostic reading. KEY POINTS: • Simultaneous multislice-accelerated diffusion-weighted imaging (sms-DWI) promises scan time minimisation. • Sms-DWI of the pancreas offers diagnostic image quality in volunteers and patients. • Sms-DWI with an acceleration factor of 2 offers high image quality. • Higher acceleration factors in sms-DWI do not provide sufficient diagnostic image quality. • ADC values may be lower in sms-DWI.

SUV-quantification of physiological lung tissue in an integrated PET/MR-system: Impact of lung density and bone tissue.

PURPOSE: The aim of the study was to investigate the influence of lung density changes as well as bone proximity on the attenuation correction of lung standardized uptake values (SUVs). METHODS AND MATERIALS: 15 patients with mostly oncologic diseases were examined in 18F-FDG-PET/CT and subsequently in a fully integrated PET/MR scanner. From each PET dataset acquired in PET/MR, four different PET reconstructions were computed using different attenuation maps (µ-maps): i) CT-based µ-map (gold standard); ii) CT-based µ-map in which the linear attenuation coefficients (LAC) of the lung tissue was replaced by the lung LAC from the MR-based segmentation method; iii) based on reconstruction ii), the LAC of bone structures was additionally replaced with the LAC from the MR-based segmentation method; iv) the vendor-provided MR-based µ-map (segmentation-based method). Those steps were performed using MATLAB. CT Hounsfield units (HU) and SUVmean was acquired in different levels and regions of the lung. Relative differences between the differently corrected PETs were computed. RESULTS: Compared to the gold standard, reconstruction ii), iii) and iv) led to a relative underestimation of SUV in the posterior regions of -9.0%, -13.4% and -14.0%, respectively. Anterior and middle regions were less affected with an overestimation of about 6-8% in reconstructions ii)-iv). CONCLUSION: It could be shown that both, differences in lung density and the vicinity of bone tissue in the µ-map may have an influence on SUV, mostly affecting the posterior lung regions.

Simulation of Tracer Dose Reduction in 18F-FDG PET/MRI: Effects on Oncologic Reading, Image Quality, and Artifacts.

The aim of our study was to evaluate the effect of stepwise-reduced doses on objective and subjective image parameters and on oncologic readings in whole-body 18F-FDG PET/MRI. Methods: We retrospectively simulated the stepwise reduction of 18F-FDG doses of 19 patients (mean age ± SD, 50.9 ± 11.7 y; mean body mass index ± SD, 22.8 ± 3.2 kg/m2) who received a whole-body PET/MRI examination from 3 to 0.5 MBq/kg of body weight (kgBW) in intervals of 0.25. Objective imaging parameters were assessed by measuring the SUV and coefficient of variation in different regions (aorta, liver, spleen, kidney, small bowel, lumbar vertebra, psoas muscle, urinary bladder) as well as the noise-equivalent counting rates in each bed position. Subjective image quality was evaluated with a masked reading of each simulated PET compared with the dose of 2 MBq/kgBW. Oncologic reading was performed first according to PERCIST in each dose and second by defining malignant lesions in doses of 2 MBq/kgBW and the maximum dose image (gold standard). The diagnostic confidence of each lesion was measured using a Likert scale. Results: With decreasing doses, regions in the mid abdomen showed a stronger decrease of SUVmean and noise-equivalent counting rates than regions in the upper abdomen (SUVmean, -45% and -15% on average in the small bowel and the liver, respectively). The coefficient of variation showed a nonlinear increase, pronounced below 1.5 MBq/kgBW. Subjective image quality was stable over a range between 1.25 and 2.75 MBq/kgBW compared with 2 MBq/kgBW. However, large photopenic areas in the mid abdomen were observed in 2 patients. In the PERCIST reading, target lesions were above the liver threshold with a stable SUVpeak in all cases down to 2 MBq/kgBW. Eighty-six of 90 lesions were identified correctly with a dose of 2 MBq/kgBW; Likert scores did not differ significantly. Conclusion: A reduction of doses in 18F-FDG PET/MRI might be possible down to 2 MBq/kgBW in oncologic whole-body examinations. The image quality in the mid abdomen seems to be more affected by lower doses than in the upper abdomen, and in single cases large photopenic areas can occur. Therefore, we do not recommend reducing doses below 3 MBq/kgBW in adults at this time.

Comparison of DCE-MRI kinetic parameters and FMISO-PET uptake parameters in head and neck cancer patients.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Self-navigated 4D cartesian imaging of periodic motion in the body trunk using partial k-space compressed sensing.

PURPOSE: To enable fast and flexible high-resolution four-dimensional (4D) MRI of periodic thoracic/abdominal motion for motion visualization or motion-corrected imaging. METHODS: We proposed a Cartesian three-dimensional k-space sampling scheme that acquires a random combination of k-space lines in the ky/kz plane. A partial Fourier-like constraint compacts the sampling space to one half of k-space. The central k-space line is periodically acquired to allow an extraction of a self-navigated respiration signal used to populate a k-space of multiple breathing positions. The randomness of the acquisition (induced by periodic breathing pattern) yields a subsampled k-space that is reconstructed using compressed sensing. Local image evaluations (coefficient of variation and slope steepness through organs) reveal information about motion resolvability. Image quality is inspected by a blinded reading. Sequence and reconstruction method are made publicly available. RESULTS: The method is able to capture and reconstruct 4D images with high image quality and motion resolution within a short scan time of less than 2 min. These findings are supported by restricted-isometry-property analysis, local image evaluation, and blinded reading. CONCLUSION: The proposed method provides a clinical feasible setup to capture periodic respiratory motion with a fast acquisition protocol and can be extended by further surrogate signals to capture additional periodic motions. Retrospective parametrization allows for flexible tuning toward the targeted applications. Magn Reson Med 78:632-644, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Diagnosing Lung Nodules on Oncologic MR/PET Imaging: Comparison of Fast T1-Weighted Sequences and Influence of Image Acquisition in Inspiration and Expiration Breath-Hold.

OBJECTIVE: First, to investigate the diagnostic performance of fast T1-weighted sequences for lung nodule evaluation in oncologic magnetic resonance (MR)/positron emission tomography (PET). Second, to evaluate the influence of image acquisition in inspiration and expiration breath-hold on diagnostic performance. MATERIALS AND METHODS: The study was approved by the local Institutional Review Board. PET/CT and MR/PET of 44 cancer patients were evaluated by 2 readers. PET/CT included lung computed tomography (CT) scans in inspiration and expiration (CTin, CTex). MR/PET included Dixon sequence for attenuation correction and fast T1-weighted volumetric interpolated breath-hold examination (VIBE) sequences (volume interpolated breath-hold examination acquired in inspiration [VIBEin], volume interpolated breath-hold examination acquired in expiration [VIBEex]). Diagnostic performance was analyzed for lesion-, lobe-, and size-dependence. Diagnostic confidence was evaluated (4-point Likert-scale; 1 = high). Jackknife alternative free-response receiver-operating characteristic (JAFROC) analysis was performed. RESULTS: Seventy-six pulmonary lesions were evaluated. Lesion-based detection rates were: CTex, 77.6%; VIBEin, 53.3%; VIBEex, 51.3%; and Dixon, 22.4%. Lobe-based detection rates were: CTex, 89.6%; VIBEin, 58.3%; VIBEex, 60.4%; and Dixon, 31.3%. In contrast to CT, inspiration versus expiration did not alter diagnostic performance in VIBE sequences. Diagnostic confidence was best for VIBEin and CTex and decreased in VIBEex and Dixon (1.2 ± 0.6; 1.2 ± 0.7; 1.5 ± 0.9; 1.7 ± 1.1, respectively). The JAFROC figure-of-merit of Dixon was significantly lower. All patients with malignant lesions were identified by CTex, VIBEin, and VIBEex, while 3 patients were false-negative in Dixon. CONCLUSION: Fast T1-weighted VIBE sequences allow for identification of patients with malignant pulmonary lesions. The Dixon sequence is not recommended for lung nodule evaluation in oncologic MR/PET patients. In contrast to CT, inspiration versus expiratory breath-hold in VIBE sequences was less crucial for lung nodule evaluation but was important for diagnostic confidence.

Defining optimal tracer activities in pediatric oncologic whole-body 18F-FDG-PET/MRI.

PURPOSE: To explore the feasibility of reducing administered tracer activities and to assess optimal activities for combined 18F-FDG-PET/MRI in pediatric oncology. METHODS: 30 18F-FDG-PET/MRI examinations were performed on 24 patients with known or suspected solid tumors (10 girls, 14 boys, age 12 ± 5.6 [1-18] years; PET scan duration: 4 min per bed position). Low-activity PET images were retrospectively simulated from the originally acquired data sets using randomized undersampling of list mode data. PET data of different simulated administered activities (0.25-2.5 MBq/kg body weight) were reconstructed with or without point spread function (PSF) modeling. Mean and maximum standardized uptake values (SUVmean and SUVmax) as well as SUV variation (SUVvar) were measured in physiologic organs and focal FDG-avid lesions. Detectability of organ structures and of focal 18F-FDG-avid lesions as well as the occurrence of false-positive PET lesions were assessed at different simulated tracer activities. RESULTS: Subjective image quality steadily declined with decreasing tracer activities. Compared to the originally acquired data sets, mean relative deviations of SUVmean and SUVmax were below 5 % at 18F-FDG activities of 1.5 MBq/kg or higher. Over 95 % of anatomic structures and all pathologic focal lesions were detectable at 1.5 MBq/kg 18F-FDG. Detectability of anatomic structures and focal lesions was significantly improved using PSF. No false-positive focal lesions were observed at tracer activities of 1 MBq/kg 18F-FDG or higher. Administration of 18F-FDG activities of 1.5 MBq/kg is, thus, feasible without obvious diagnostic shortcomings, which is equivalent to a dose reduction of more than 50 % compared to current recommendations. CONCLUSION: Significant reduction in administered 18F-FDG tracer activities is feasible in pediatric oncologic PET/MRI. Appropriate activities of 18F-FDG or other tracers for specific clinical questions have to be further established in selected patient populations.

Decoding Intratumoral Heterogeneity of Breast Cancer by Multiparametric In Vivo Imaging: A Translational Study.

Differential diagnosis and therapy of heterogeneous breast tumors poses a major clinical challenge. To address the need for a comprehensive, noninvasive strategy to define the molecular and functional profiles of tumors in vivo, we investigated a novel combination of metabolic PET and diffusion-weighted (DW)-MRI in the polyoma virus middle T antigen transgenic mouse model of breast cancer. The implementation of a voxelwise analysis for the clustering of intra- and intertumoral heterogeneity in this model resulted in a multiparametric profile based on [(18)F]Fluorodeoxyglucose ([(18)F]FDG)-PET and DW-MRI, which identified three distinct tumor phenotypes in vivo, including solid acinar, and solid nodular malignancies as well as cystic hyperplasia. To evaluate the feasibility of this approach for clinical use, we examined estrogen receptor-positive and progesterone receptor-positive breast tumors from five patient cases using DW-MRI and [(18)F]FDG-PET in a simultaneous PET/MRI system. The postsurgical in vivo PET/MRI data were correlated to whole-slide histology using the latter traditional diagnostic standard to define phenotype. By this approach, we showed how molecular, structural (microscopic, anatomic), and functional information could be simultaneously obtained noninvasively to identify precancerous and malignant subtypes within heterogeneous tumors. Combined with an automatized analysis, our results suggest that multiparametric molecular and functional imaging may be capable of providing comprehensive tumor profiling for noninvasive cancer diagnostics. Cancer Res; 76(18); 5512-22. ©2016 AACR.