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When increasing the PET acquisition time to match the longer MRI protocol in simultaneous PET/MR, the injected PET tracer dose can possibly be lowered to reduce radiation exposure. Moreover, applying new commercially available time-of-flight (TOF) block sequential regularized expectation maximization (BSREM)–based reconstruction algorithms could allow for further dose reductions. The purpose of this study was to find the minimal dose of the tracer targeting the prostate specific membrane antigen (68Ga-PSMA-11) for a dedicated 15-min pelvic PET/MR scan that still matches the image quality of a reference 3-min scan at 100% (150 MBq) dose. In this retrospective analysis, 25 patients were included. PET emission datasets were edited to simulate stepwise reductions of injected tracer dose. Reference TOF ordered subset expectation maximum (OSEM) and new TOF BSREM reconstructions were performed and differences in the resulting PET images were visually and quantitatively assessed. Visually, TOF BSREM reconstructions with relatively high regularization parameter (β) values are preferred. Quantitatively, however, high β-values result in lower lesion maximum standardized uptake values (SUVmax) compared to the reference. A β-value of 550 was considered the optimal compromise for the lowest possible 10% dose reconstructions, resulting in comparable visual assessment and lesion SUVmax. This study indicates that the injected 68Ga-PSMA-11 tracer dose for a standard 3-min PET scan can be reduced to approximately 10% (15 MBq) when the PET acquisition time is matched to the 15-min pelvic MRI protocol, and when reconstructed with TOF BSREM using β = 550. This decreases the effective dose from 3.54 to 0.35 mSv. • Low-dose dedicated pelvic 68 Ga-PSMA-11 PET/MR reduces radiation exposure for patients. • Retrospective study investigating the minimal dose needed for adequate image quality for 15-min PET frames over the pelvis showed using quantitative and qualitative analysis that a substantial dose reduction is possible without significant loss of image quality when using the TOF BSREM reconstruction algorithm. • With the introduction of low-dose pelvic 68 Ga-PSMA-11 PET/MR, new potential applications of 68 Ga-PSMA-11 PET for local staging or investigation of equivocal MRI findings could become applicable, even for patients without confirmed prostate cancer.

Radical prostatectomy with extended pelvic lymph node dissection (ePLND) is a curative treatment option for patients with clinically significant localised prostate cancer. The decision to perform an ePLND can be challenging because the overall incidence of lymph node metastasis is relatively low and ePLND is not free of complications. Using current clinical nomograms to identify patients with nodal involvement, approximately 75–85% of ePLNDs performed are negative. The aim of this study was to assess the added value of 68Ga-PSMA-11 PET in predicting lymph node metastasis in men with intermediate- or high-risk prostate cancer. 68Ga-PSMA-11 PET scans of 60 patients undergoing radical prostatectomy with ePLND were reviewed for qualitative (visual) assessment of suspicious nodes and assessment of quantitative parameters of the primary tumour in the prostate (SUVmax, total activity (PSMAtotal) and PSMA positive volume (PSMAvol)). Ability of quantitative PET parameters to predict nodal metastasis was assessed with receiver operating characteristics (ROC) analysis. A multivariable logistic regression model combining PSA, Gleason score, visual nodal status on PET and primary tumour PSMAtotal was built. Net benefit at each risk threshold was compared with five nomograms: MSKCC nomogram, Yale formula, Roach formula, Winter nomogram and Partin tables (2016). Overall, pathology of ePLND specimens revealed 31 pelvic metastatic lymph nodes in 12 patients. 68Ga-PSMA-11 PET visual analysis correctly detected suspicious nodes in 7 patients, yielding a sensitivity of 58% and a specificity of 98%. The area under the ROC curve for primary tumour SUVmax was 0.70, for PSMAtotal 0.76 and for PSMAvol 0.75. The optimal cut-off for nodal involvement was PSMAtotal > 49.1. The PET model including PSA, Gleason score and quantitative PET parameters had a persistently higher net benefit compared with all clinical nomograms. Our model combining PSA, Gleason score and visual lymph node analysis on 68Ga-PSMA-11 PET with PSMAtotal of the primary tumour showed a tendency to improve patient selection for ePLND over the currently used clinical nomograms. Although this result has to be validated, 68Ga-PSMA-11 PET showed the potential to reduce unnecessary surgical procedures in patients with intermediate- or high-risk prostate cancer.

Background The purpose of this study was to assess the impact of vendor-provided atlas-based MRAC on FDG PET/MR for the evaluation of Alzheimer’s disease (AD) by using simulated images. Methods We recruited 47 patients, from two institutions, who underwent PET/CT and PET/MR (GE SIGNA) examination for oncological staging. From the PET raw data acquired on PET/MR, two FDG-PET series were generated, using vendor-provided MRAC (atlas-based) and CTAC. The following simulation steps were performed in MNI space: After spatial normalization and smoothing of the PET datasets, we calculated the error map for each patient, PETMRAC/PETCTAC. We multiplied each of these 47 error maps with each of the 203 Alzheimer’s Disease Neuroimaging Initiative (ADNI) cases after the identical normalization and smoothing. This resulted in 203*47 = 9541 datasets. To evaluate the probability of AD in each resulting image, a cumulative t-value was calculated automatically using commercially-available software (PMOD PALZ) which has been used in multiple large cohort studies. The diagnostic accuracy for the discrimination of AD and predicting progression from mild cognitive impairment (MCI) to AD were evaluated in simulated images compared with ADNI original images. Results The accuracy and specificity for the discrimination of AD-patients from normal controls were not substantially impaired, but sensitivity was slightly impaired in 5 out of 47 datasets (original vs. error; 83.2% [CI 75.0%-89.0%], 83.3% [CI 74.2%-89.8%] and 83.1% [CI 75.6%-88.3%] vs. 82.7% [range 80.4–85.0%], 78.5% [range 72.9–83.3%,] and 86.1% [range 81.4–89.8%]). The accuracy, sensitivity and specificity for predicting progression from MCI to AD during 2-year follow-up was not impaired (original vs. error; 62.5% [CI 53.3%-69.3%], 78.8% [CI 65.4%-88.6%] and 54.0% [CI 47.0%-69.1%] vs. 64.8% [range 61.5–66.7%], 75.7% [range 66.7–81.8%,] and 59.0% [range 50.8–63.5%]). The worst 3 error maps show a tendency towards underestimation of PET scores. Conclusion FDG-PET/MR based on atlas-based MR attenuation correction showed similar diagnostic accuracy to the CT-based method for the diagnosis of AD and the prediction of progression of MCI to AD using commercially-available software, although with a minor reduction in sensitivity.

High-intensity focused ultrasound (HIFU) is a promising new modality for the treatment of localized prostate cancer (PCa). Follow-up of patients is recommended with biopsies and multiparametric MRI (mpMRI). However, mpMRI in the postinterventional setting is often false-negative. It was our aim to investigate if the new tracer targeting the prostate-specific membrane antigen (68Ga-PSMA-11) could be used to localize recurrent disease with PET/MR in patients with discrepant findings between mpMRI and template biopsies. Methods: Interim analysis was performed of the first 10 patients scanned between September 2016 and May 2018 with positive template biopsy and negative mpMRI after HIFU from an ongoing clinical trial (NCT02265159). All patients underwent 68Ga-PSMA-11 PET/MRI within 3 mo. Four prostatic quadrants were defined, and for every quadrant suspicion for recurrence was rated on a 5-point Likert scale from definitely no recurrence (1) to highly suspected of recurrence (5), with 4 used as a cutoff for suspected disease based on PET/MRI by a masked reader. 68Ga-PSMA-11 uptake of suspected lesions and background areas was measured with the SUVmax The apparent diffusion coefficient values of lesions and background were given for each segment. PET/MRI scans were compared with the template biopsy results, including corresponding Gleason scores (GS), number of positive cores, and tumor length. Results: The quadrant-based sensitivity, specificity, and positive and negative predictive values for PET/MRI were 55%, 100%, 100%, and 85%, respectively. Patient-based PET/MRI was negative in 4 cases with GS 3 + 4 and a tumor length between 0.1 and 3 mm. All tumor lesions with GS 4 + 3 or higher were detected on PET/MRI. Conclusion: Our preliminary results indicate that 68Ga-PSMA-11-PET/MR has the potential to localize PCa recurrence after HIFU occult on mpMRI.

Background Brown adipose tissue (BAT) is a thermogenic tissue which can generate heat in response to mild cold exposure. As it constitutes a promising target in the fight against obesity, we need reliable techniques to quantify its activity in response to therapeutic interventions. The current standard for the quantification of BAT activity is [18F]FDG PET/CT. Various sequences in magnetic resonance imaging (MRI), including those measuring its relative fat content (fat fraction), have been proposed and evaluated in small proof-of-principle studies, showing diverging results. Here, we systematically compare the predictive value of adipose tissue fat fraction measured by MRI to the results of [18F]FDG PET/CT. Methods We analyzed the diagnostic reliability of MRI measured fat fraction (FF) for the estimation of human BAT activity in two cohorts of healthy volunteers participating in two prospective clinical trials (NCT03189511, NCT03269747). In both cohorts, BAT activity was stimulated by mild cold exposure. In cohort 1, we performed [18F]FDG PET/MRI; in cohort 2, we used [18F]FDG PET/CT followed by MRI. Fat fraction was determined by 2-point Dixon and 6-point Dixon measurement, respectively. Fat fraction values were compared to SUVmean in the corresponding tissue depot by simple linear regression. Results In total, 33 male participants with a mean age of 23.9 years and a mean BMI of 22.8 kg/m2 were recruited. In 32 participants, active BAT was visible. On an intra-individual level, FF was significantly lower in high-SUV areas compared to low-SUV areas (cohort 1: p

The goal of this study was to determine the level of clinically acceptable 18F-FDG dose reduction in time-of-flight PET/MRI in patients with breast cancer. Methods: Twenty-six consecutive women with histologically proven breast cancer were analyzed (median age, 51 y; range, 34-83 y). Simulated dose-reduced PET images were generated by unlisting the list-mode data on PET/MRI. The acquired 20-min PET frame was reconstructed in 5 ways: a reconstruction of the first 2 min with 3 iterations and 28 subsets for reference, and reconstructions simulating 100%, 20%, 10%, and 5% of the original dose. General image quality and artifacts, image sharpness, image noise, and lesion detectability were analyzed using a 4-point scale. Qualitative parameters were compared using the nonparametric Friedman test for multiple samples and the Wilcoxon signed-rank test for paired samples. Different groups of independent samples were compared using the Mann-Whitney U test. Results: Overall, 355 lesions (71 lesions with 5 different reconstructions each) were evaluated. The 20-min reconstruction with 100% injected dose showed the best results in all categories. For general image quality and artifacts, image sharpness, and noise, the reconstructions with a simulated dose of 20% and 10% were significantly better than the 2-min reconstructions (P ≤ 0.001). Furthermore, 20%, 10%, and 5% reconstructions did not yield results different from those of the 2-min reconstruction for detectability of the primary lesion. For 10% of the injected dose, a calculated mean dose of 22.6 ± 5.5 MBq (range, 17.9-36.9 MBq) would have been applied, resulting in an estimated whole-body radiation burden of 0.5 ± 0.1 mSv (range, 0.4-0.7 mSv). Conclusion: Ten percent of the standard dose of 18F-FDG (reduction of ≤90%) results in clinically acceptable PET image quality in time-of-flight PET/MRI. The calculated radiation exposure would be comparable to the effective dose of a single digital mammogram. A reduction of radiation burden to this level might justify partial-body examinations with PET/MRI for dedicated indications.

Purpose To determine the level of clinically acceptable reduction in injected fluorine 18 (18F) fluorodeoxyglucose (FDG) dose in time-of-flight (TOF)-positron emission tomography(PET)/magnetic resonance (MR) imaging by using silicon photomultiplier (SiPM) detectors compared with TOF-PET/computed tomography (CT) using Lu1.8Y0.2SiO5(Ce), or LYSO, detectors in patients with different body mass indexes (BMIs). Materials and Methods Patients were enrolled in this study as part of a larger prospective study with a different purpose than evaluated in this study (NCT02316431). All patients gave written informed consent prior to inclusion into the study. In this study, 74 patients with different malignant diseases underwent sequential whole-body TOF-PET/CT and TOF-PET/MR imaging. PET images with simulated reduction of injected 18F-FDG doses were generated by unlisting the list-mode data from PET/MR imaging. Two readers rated the image quality of whole-body data sets, as well as the image quality in each body compartment, and evaluated the conspicuity of malignant lesions. Results The image quality with 70% or 60% of the injected dose of 18F-FDG at PET/MR imaging was comparable to that at PET/CT. With 50% of the injected dose, comparable image quality was maintained among patients with a BMI of less than 25 kg/m2. PET images without TOF reconstruction showed higher artifact scores and deteriorated sharpness than those with TOF reconstruction. Conclusion Sixty percent of the usually injected 18F-FDG dose (reduction of up to 40%) in patients with a BMI of more than 25 kg/m2 results in clinically adequate PET image quality in TOF-PET/MR imaging performed by using SiPM detectors. Additionally, in patients with a BMI of less than 25 kg/m2, 50% of the injected dose may safely be used. © RSNA, 2017 Online supplemental material is available for this article.

BACKGROUND To compare the diagnostic accuracy of PET/MR and PET/CT in patients with suspected occult primary tumors. METHODS This prospective study was approved by the institutional review board. Sequential PET/CT-MR was performed in 43 patients (22 male subjects; median age, 58 years; range, 20-86 years) referred for suspected occult primary tumors. Patients were assessed with PET/CT and PET/MR for the presence of a primary tumor, lymph node metastases, and distant metastases. Wilcoxon signed-rank test was performed to compare the diagnostic accuracy of PET/CT and PET/MR. RESULT According to the standard of reference, a primary lesion was found in 14 patients. In 16 patients, the primary lesion remained occult. In the remaining 13 patients, lesions proved to be benign. PET/MR was superior to PET/CT for primary tumor detection (sensitivity/specificity, 0.85/0.97 vs 0.69/0.73; P = 0.020) and comparable to PET/CT for the detection of lymph node metastases (sensitivity/specificity, 0.93/1.00 vs 0.93/0.93; P = 0.157) and distant metastases (sensitivity/specificity, 1.00/0.97 vs 0.82/1.00; P = 0.564). PET/CT tended to misclassify physiologic FDG uptake as malignancy compared with PET/MR (8 patients vs 1 patient). CONCLUSIONS PET/MR outperforms PET/CT in the workup of suspected occult malignancies. PET/MR may replace PET/CT to improve clinical workflow.

Background Positron emission tomography (PET) is increasingly applied for in vivo brown adipose tissue (BAT) research in healthy volunteers. To limit the radiation exposure, the injected 18F-FDG tracer dose should be as low as possible. With simultaneous PET/MR imaging, the radiation exposure due to computed tomography (CT) can be avoided, but more importantly, the PET acquisition time can often be increased to match the more extensive magnetic resonance (MR) imaging protocol. The potential gain in detected coincidence counts, due to the longer acquisition time, can then be applied to decrease the injected tracer dose. The aim of this study was to investigate the minimal 18F-FDG dose for a 10-min time-of-flight (TOF) PET/MR acquisition that would still allow accurate quantification of supraclavicular BAT volume and activity. Methods Twenty datasets from 13 volunteers were retrospectively included from a prospective clinical study. PET emission datasets were modified to simulate step-wise reductions of the original 75 MBq injected dose. The resulting PET images were visually and quantitatively assessed and compared to a 4-min reference scan. For the visual assessment, the image quality and artifacts were scored using a 5-point and a 3-point Likert scale. For the quantitative analysis, image noise and artifacts, BAT metabolic activity, BAT metabolic volume (BMV), and total BAT glycolysis (TBG) were investigated. Results The visual assessment showed still good image quality for the 35%, 30%, and 25% activity reconstructions with no artifacts. Quantitatively, the background noise was similar to the reference for the 35% and 30% activity reconstructions and the artifacts started to increase significantly in the 25% and lower activity reconstructions. There was no significant difference in supraclavicular BAT metabolic activity, BMV, and TBG between the reference and the 35% to 20% activity reconstructions. Conclusions This study indicates that when the PET acquisition time is matched to the 10-min MRI protocol, the injected 18F-FDG tracer dose can be reduced to approximately 19 MBq (25%) while maintaining image quality and accurate supraclavicular BAT quantification. This could decrease the effective dose from 1.4 mSv to 0.36 mSv.

Identification of pretherapeutic predictive markers in gastro-esophageal cancer is essential for individual-oriented treatment. This study evaluated the relationship of multimodality parameters derived from intravoxel incoherent motion method (IVIM), 18F-FDG-positron emission tomography (PET), computed tomography (CT) perfusion and dynamic contrast enhanced magnetic resonance imaging (MRI) in patients with gastro-esophageal cancer and investigated their histopathological correlation.Thirty-one consecutive patients (28 males; median age 63.9 years; range 37-84 years) with gastro-esophageal adenocarcinoma (N.=22) and esophageal squamous cell carcinoma (N.=9) were analyzed. IVIM parameters: pseudodiffusion (D*), perfusion fraction (fp), true diffusion (D) and the threshold b-value (bval); PET-parameters: SUVinfmax/inf, metabolic tumor volume (MTV) and total lesion glycolysis (TLG); CT perfusion parameters: blood flow (BF), blood volume (BV) and mean transit time (MTT); and MR perfusion parameters: time to enhance, positive enhancement integral, time-to-peak (TTP), maximum-slope-of-increase, and maximum-slope-of-decrease were determined, and correlated to each other and to histopathology.IVIM and PET parameters showed significant negative correlations: MTV and bval (rinfs/inf=-0.643, P=0.002), TLG and bval (rinfs/inf=-0.699, P0.01) and TLG and fp (rinfs/inf=-0.577, P=0.006). Positive correlation was found for TLG and D (rinfs/inf=0.705, P=0.000). Negative correlation was found for bval and staging (rinfs/inf=0.590, P=0.005). Positive correlation was found for positive enhancement interval and BV (rinfs/inf=0.547, P=0.007), BF and regression index (rinfs/inf=0.753, P=0.005) and for time-to-peak and staging (rinfs/inf=0.557, P=0.005).IVIM parameters (bval, fp, D) provide quantitative information and correlate with PET parameters (MTV, TLG) and staging. IVIM might be a useful tool for additional characterization of gastro-esophageal cancer.

Our objective was to determine clinically the value of time-of-flight (TOF) information in reducing PET artifacts and improving PET image quality and accuracy in simultaneous TOF PET/MR scanning. A total 65 patients who underwent a comparative scan in a simultaneous TOF PET/MR scanner were included. TOF and non-TOF PET images were reconstructed, clinically examined, compared and scored. PET imaging artifacts were categorized as large or small implant-related artifacts, as dental implant-related artifacts, and as implant-unrelated artifacts. Differences in image quality, especially those related to (implant) artifacts, were assessed using a scale ranging from 0 (no artifact) to 4 (severe artifact). A total of 87 image artifacts were found and evaluated. Four patients had large and eight patients small implant-related artifacts, 27 patients had dental implants/fillings, and 48 patients had implant-unrelated artifacts. The average score was 1.14 ± 0.82 for non-TOF PET images and 0.53 ± 0.66 for TOF images (p

Purpose: The aim of the study was to investigate the potential of diffusion-weighted magnetic resonance imaging (DW-MRI) and 3′-dexoy-3′-[18F]fluorothymidine ([18F]FLT) positron emission tomography (PET) as early biomarkers of treatment response of 5-fluorouracil (5-FU) in a syngeneic rat model of colorectal cancer liver metastases. Procedures: Wag/Rij rats with intrahepatic syngeneic CC531 tumors were treated with 5-FU (15, 30, or 60 mg/kg in weekly intervals). Before treatment and at days 1, 3, 7, and 14 after treatment rats underwent DW-MRI and [18F]FLT PET. Tumors were analyzed immunohistochemically for Ki67, TK1, and ENT1 expression. Results: 5-FU inhibited the growth of CC531 tumors in a dose-dependent manner. Immunohistochemical analysis did not show significant changes in Ki67, TK1, and ENT1 expression. However, [18F]FLT SUVmean and SUVmax were significantly increased at days 4 and 7 after treatment with 5-FU (60 mg/kg) and returned to baseline at day 14 (SUVmax at days −1, 4, 7, and 14 was 1.1 ± 0.1, 2.3 ± 0.5, 2.3 ± 0.6, and 1.5 ± 0.4, respectively). No changes in [18F]FLT uptake were observed in the nontreated animals. Furthermore, the apparent diffusion coefficient (ADCmean) did not change in 5-FU-treated rats compared to untreated rats. Conclusion: This study suggests that 5-FU treatment induces a flare in [18F]FLT uptake of responsive CC531 tumors in the liver, while the ADCmean did not change significantly. Future studies in larger groups are warranted to further investigate whether [18F]FLT PET can discriminate between disease progression and treatment response.

Purpose The purpose of this study was to evaluate the effect of defective positron emission tomography (PET) detectors on clinical PET image quality in simultaneous PET/magnetic resonance imaging (MRI) for both time-of-flight (TOF) and non-TOF reconstructed images.

The purpose of this work was to improve dynamic contrast enhanced MRI (DCE-MRI) of liver lesions by removing motion corrupted images as identified by a structural similarity (SSIM) algorithm, and to assess the effect of this correction on the pharmacokinetic parameter Ktrans using automatically determined arterial input functions (AIFs). Fifteen patients with colorectal liver metastases were measured twice with a T1 weighted multislice 2D FLASH sequence for DCE-MRI (time resolution 1.2 s). AIFs were automatically derived from contrast inflow in the aorta of each patient. Thereafter, SSIM identified motion corrupted images of the liver were removed from the DCE dataset. From this corrected data set Ktrans and its reproducibility were determined. Using the SSIM algorithm a median fraction of 46% (range 37–50%) of the liver images in DCE time series was labeled as motion distorted. Rejection of these images resulted in a significantly lower median Ktrans (p

PURPOSE: A relatively high signal for choline-containing compounds (total choline, tCho) is commonly found in (1) H MR spectra of malignant tumors, but it is unclear if this also occurs in tumors in the liver. We evaluated the potential of the tCho signal in single voxel (1) H MR spectra of the human liver to assess metastases of colorectal cancers. EXPERIMENT: MR spectra of an 8 cm(3) PRESS-localized voxel were obtained at 3 T from the livers of 12 healthy volunteers and from metastatic lesions in 20 patients in two different sessions. To correct for motion artifacts, sequentially recorded spectra were individually phased and frequency aligned before averaging. Spectra were analyzed using LCModel and tissue levels estimated by water referencing. Repeatability was assessed with Bland-Altman analyses. To estimate tumor necrosis, diffusion-weighted imaging of the liver was performed. High resolution magic angle spinning (HRMAS) spectra of tumor and normal liver samples were obtained at 11.7 T. RESULTS: With increasing tumor volumes, tCho levels decreased, indicating a partial volume effect. Mean tCho content in tumors larger than the PRESS voxel (>8 cm(3) ) was significantly lower (p < 0.01) than for normal liver: 1.6 (range 0.0-3.4) versus 6.9 (range 4.9-11.1) mmol/kg wet weight, while it was comparable for tumors smaller than 8 cm(3) : 7.0 (range 3.8-9.3) mmol/kg. The higher 90th percentile apparent diffusion coefficient value in the larger lesions indicates more necrosis. Measurement repeatability was average in normal livers and poor in tumors. HRMAS did not show substantial differences in choline-containing compounds between normal liver and metastasis. CONCLUSION: An increased tCho content was not observed in (1) H MR spectra of liver metastasis of colorectal cancer, compared with normal liver. This may be due to the background of a high tCho signal in spectra of normal liver or to an intrinsic lower tCho content in these tumors, but is most likely the result of necrosis in metastatic tumor tissue.

BACKGROUND Positron emission tomography (PET) / computed tomography (CT) is among the most frequently used imaging modalities for initial staging of gastro-oesophageal (GE) cancer, whereas CT-perfusion (CTP) provides different multiparametric information. This proof of concept study compares CTP- and PET-parameters in patients with GE cancer to evaluate correlations and a possible prognostic value of a combined PET/CTP imaging procedure. METHODS A total of 31 patients with F-18-FDG-PET/CT and CTP studies were prospectively analysed. Patients had adenocarcinoma (n = 22) and oesophageal squamous cell carcinoma (SCC, n = 9). Imaging was performed before start of treatment. CTP parameters [blood flow (BF), blood volume (BV), mean transit time (MTT)] and metabolic parameters [(maximum and mean standardised uptake values and standard deviation (SUVmax, SUVmean, SUVsd), metabolic tumour volume (MTV) and tumour lesion glycolysis (TLG)], as well as flow metabolic product [FMP (BF × SUVmax)] were determined and their relationship was compared. Additionally their association to clinical parameters (differentiation grading, staging, HER2-status, follow-up status) and to histopathological regression (post-neoadjuvant regression grading) was evaluated. RESULTS Correlation between parameters of both modalities was significant between MTT and MTV (r = 0.375, p = 0.038); no other significant correlation was found. Patients with complete histopathological regression showed significantly lower BF and BV than patients with nearly complete or partial response. TLG and regression grading showed significant correlation with staging. All other quantitative parameters for CTP and PET data did not correlate significantly with histopathological regression grading, differentiation or staging. CONCLUSIONS The combination of PET and CTP parameters (FMP) showed no significant prognostic value. Significant correlations were only found between MTT and MTV, which indicates a possible perfusional/metabolic coupling. Therefore, pre-therapeutic CTP and PET- parameters provide complementary information about the pre-therapeutic tumour status and are not interchangeable. Only CTP parameters might be able to predict complete histopathological regression. On the other hand, only PET parameters are correlated with staging.

A relatively high signal for choline-containing compounds (total choline, tCho) is commonly found inMR spectra of an 8 cmWith increasing tumor volumes, tCho levels decreased, indicating a partial volume effect. Mean tCho content in tumors larger than the PRESS voxel (8 cmAn increased tCho content was not observed in

Purpose: The aim of this study was to evaluate the feasibility of attenuation correction (AC) for cardiac 18F-labelled fluorodeoxyglucose (FDG) positron emission tomography (PET) using MR-based attenuation maps. Methods: We included 23 patients with no known cardiac history undergoing whole-body FDG PET/CT imaging for oncological indications on a PET/CT scanner using time-of-flight (TOF) and subsequent whole-body PET/MR imaging on an investigational hybrid PET/MRI scanner. Data sets from PET/MRI (with and without TOF) were reconstructed using MR AC and semi-quantitative segmental (20-segment model) myocardial tracer uptake (per cent of maximum) and compared to PET/CT which was reconstructed using CT AC and served as standard of reference. Results: Excellent correlations were found for regional uptake values between PET/CT and PET/MRI with TOF (n = 460 segments in 23 patients; r = 0.913; p

The goal of this study was to determine the level of clinically acceptable

Purpose To determine the level of clinically acceptable reduction in injected fluorine 18 (

Metalic implants may affect attenuation correction (AC) in PET/MR imaging. The purpose of this study was to evaluate the effect of susceptibility artifacts related to metallic implants on adjacent metabolically active lesions in clinical simultaneous PET/MR scanning for both time-of-flight (TOF) and non-TOF reconstructed PET images. Methods: We included 27 patients without implants but with confirmed 18F-FDG-avid lesions adjacent to common implant locations. In all patients, a clinically indicated whole-body 18F-FDG PET/MR scan was acquired. Baseline non-TOF and TOF PET images were reconstructed. Reconstruction was repeated after the introduction of artificial signal voids in the AC map to simulate metallic implants in standard anatomic areas. All reconstructed images were qualitatively and quantitatively assessed and compared with the baseline images. Results: In total, 51 lesions were assessed. In 40 and 50 of these cases (non-TOF and TOF, respectively), the detectability of the lesions did not change; in 9 and 1 cases, the detectability changed; and in 2 non-TOF cases, the lesions were no longer visible after the introduction of metallic artifacts. The inclusion of TOF information significantly reduced artifacts due to simulated implants in the femoral head, sternum, and spine (P = 0.01, 0.01, and 0.03, respectively). It also improved image quality in these locations (P = 0.02, 0.01, and 0.01, respectively). The mean percentage error was -3.5% for TOF and -4.8% for non-TOF reconstructions, meaning that the inclusion of TOF information reduced the percentage error in SUVmax by 28.5% (P < 0.01). Conclusion: Qualitatively, there was a significant reduction of artifacts in the femoral head, sternum, and spine. There was also a significant qualitative improvement in image quality in these locations. Furthermore, our study indicated that simulated susceptibility artifacts related to metallic implants have a significant effect on small, moderately 18F-FDG-avid lesions near the implant site that possibly may go unnoticed without TOF information. On larger, highly 18F-FDG-avid lesions, the metallic implants had only a limited effect. The largest significant quantitative difference was found in artifacts of the sternum. There was only a weak inverse correlation between lesions affected by artifacts and distance from the implant.

Background The purpose of this study was to compare the diagnostic accuracy of positron emission tomography (PET)/MRI with PET/CT for local resectability of head and neck cancer. Methods Sequential contrast-enhanced PET/CT-MRI was performed in 58 patients referred for the staging or restaging of head and neck cancer. Tumors were assessed with PET/CT and PET/MRI for the presence of resectability-defining factors: T4b status (mediastinal invasion, invasion of the prevertebral space, and vascular encasement), and another 8 findings that would imply obstacles for surgical cure (invasion of the laryngeal cartilage, invasion of the preepiglottic fat pad, perineural spread, orbital invasion, bone infiltration, skull base invasion, dural infiltration, and invasion of the brachial plexus). Results The sensitivity/specificity/accuracy of local resectability-defining factors of PET/CT and PET/MRI was 0.92/0.99/0.98 and 0.98/0.99/0.99 (P = .727), respectively, per lesion, and 0.96/0.87/0.91 and 0.96/0.90/0.93 (P = .687), respectively, per patient. Conclusion Both contrast-enhanced PET/MRI and contrast-enhanced PET/CT can serve as reliable examinations for defining local resectability of head and neck cancer.

The recently available integrated PET/MR imaging can offer significant additional advances in clinical imaging. The purpose of this study was to compare the PET performance between a PET/CT scanner and an integrated TOF-PET/MR scanner concerning image quality parameters and quantification in terms of SUV as a function of acquisition time (a surrogate of dose). Five brain and five whole body patients were included in the study. The PET/CT scan was used as a reference and the PET/MR acquisition time was consecutively adjusted, taking into account the decay between the scans in order to expose both systems to the same amount of emitted signal. The acquisition times were then retrospectively reduced to assess the performance of the PET/MRI for lower count rates. Image quality, image sharpness, artifacts and noise were evaluated. SUV measurements were taken in the liver and in white matter to compare quantification. Quantitative evaluation showed good correlation between PET/CT and PET/MR brain SUVs. Liver correlation was lower, with uptake underestimation in PET/MR, partially justified by bio-redistribution. The clinical evaluation showed that PET/MR offers higher image quality and sharpness with lower levels of noise and artefacts compared to PET/CT with reduced acquisition times for whole body scans, while for brain scans there is no significant difference. The PET-component of the TOF-PET/MR showed higher image quality compared to PET/CT as tested with reduced imaging times. However, these results account mainly for body imaging, while no significant difference were found in brain imaging. This overall higher image quality suggests that the acquisition time or injected activity can be reduced by at least 37% on the PET/MR scanner.

Accurate attenuation correction (AC) on PET/MR is still challenging. The purpose of this study was to evaluate the clinical feasibility of AC based on fast zero-echo-time (ZTE) MR imaging by comparing it the default atlas-based AC on a clinical PET/MR scanner. Methods: We recruited 10 patients with malignant diseases not located on the brain. In all patients, a clinically-indicated whole-body 18F-FDG-PET/CT was acquired. In addition, a head PET/MR scan (GE SIGNA TOF-PET/MR) was performed voluntarily. For each patient, two AC maps were generated from the MR images. One was Atlas-AC, derived from T1-weighted LAVA-FLEX images (clinical standard). The other was ZTE-AC, derived from proton-density-weighted ZTE images by applying tissue segmentation and assigning continuous attenuation values to the bone. The AC map generated by PET/CT was used as silver standard. Based on each AC map, PET images were reconstructed from identical raw data on the PET/MR scanner. All PET images were normalized to the SPM5 PET template. After that, these images were qualified visually and quantified in 67 volumes-of-interest (VOIs; automated anatomical labeling (AAL), atlas). Relative differences (%diff) and absolute relative differences (|%diff|) between PET images based on each AC were calculated. FDG uptake in all 670 VOIs and generalized merged VOIs were compared using paired t-test. Results: Qualitative analysis shows that ZTE-AC was robust to patient variability. Nevertheless, misclassification of air and bone in mastoid and nasal areas led the overestimation of PET in the temporal lobe and cerebellum (%diff of ZTE-AC; 2.46±1.19% and 3.31±1.70%, respectively). The |%diff| of all 670 VOIs on ZTE was improved by approximately 25% compared to Atlas-AC (ZTE-AC vs. Atlas-AC; 1.77±1.41% vs. 2.44±1.63%, P < 0.01). In two out of seven generalized VOIs, |%diff| on ZTE-AC were significantly smaller than Atlas-AC (ZTE-AC vs. Atlas-AC; Insula and cingulate, 1.06±0.67% vs. 2.22±1.10%, P < 0.01; central structure, 1.03±0.99% vs. 2.54±1.20%, P < 0.05). Conclusion: The ZTE-AC could provide more accurate AC than clinical Atlas-AC by improving the estimation of head skull attenuation. The misclassification in mastoid and nasal areas must be addressed to prevent the overestimation of PET in regions near the skull base.

The purpose of this work was to improve dynamic contrast enhanced MRI (DCE-MRI) of liver lesions by removing motion corrupted images as identified by a structural similarity (SSIM) algorithm, and to assess the effect of this correction on the pharmacokinetic parameter K

Simultaneous PET/MRI was introduced into the commercial market only a few years ago, and its availability is currently gaining momentum with the introduction of a second-generation PET/MRI system from an additional vendor. Furthermore, there is still an increasing interest in its potential in clinical and research applications. Despite very early technical infancy problems, which meanwhile have been solved, there are still different limitations that have to be worked around in daily routine responsibly by the physicists and physicians. This article gives an overview over the most common technical, logistical, and clinical limitations; artifacts; and pitfalls, without any claim for completeness. The readers will not only learn the background of the limitation but also partly learn about possible solutions. At the end of each paragraph, the readers will find a short summary for an easier overview of the topics discussed.

In this work, we assessed the feasibility of attenuation correction (AC) based on a multi-atlas-based method (m-Atlas) by comparing it with a clinical AC method (single-atlas-based method [s-Atlas]), on a time-of-flight (TOF) PET/MRI scanner.We enrolled 15 patients. The median patient age was 59 y (age range, 31-80). All patients underwent clinically indicated whole-body (18)F-FDG PET/CT for staging, restaging, or follow-up of malignant disease. All patients volunteered for an additional PET/MRI scan of the head (no additional tracer being injected). For each patient, 3 AC maps were generated. Both s-Atlas and m-Atlas AC maps were generated from the same patient-specific LAVA-Flex T1-weighted images being acquired by default on the PET/MRI scanner during the first 18 s of the PET scan. An s-Atlas AC map was extracted by the PET/MRI scanner, and an m-Atlas AC map was created using a Web service tool that automatically generates m-Atlas pseudo-CT images. For comparison, the AC map generated by PET/CT was registered and used as a gold standard. PET images were reconstructed from raw data on the TOF PET/MRI scanner using each AC map. All PET images were normalized to the SPM5 PET template, and (18)F-FDG accumulation was quantified in 67 volumes of interest (VOIs; automated anatomic labeling atlas). Relative (%diff) and absolute differences (|%diff|) between images based on each atlas AC and CT-AC were calculated. (18)F-FDG uptake in all VOIs and generalized merged VOIs were compared using the paired t test and Bland-Altman test.The range of error on m-Atlas in all 1,005 VOIs was -4.99% to 4.09%. The |%diff| on the m-Atlas was improved by about 20% compared with s-Atlas (s-Atlas vs. m-Atlas: 1.49% ± 1.06% vs. 1.21% ± 0.89%, P0.01). In generalized VOIs, %diff on m-Atlas in the temporal lobe and cerebellum was significantly smaller (s-Atlas vs. m-Atlas: temporal lobe, 1.49% ± 1.37% vs. -0.37% ± 1.41%, P0.01; cerebellum, 1.55% ± 1.97% vs. -1.15% ± 1.72%, P0.01).The errors introduced using either s-Atlas or m-Atlas did not exceed 5% in any brain region investigated. When compared with the clinical s-Atlas, m-Atlas is more accurate, especially in regions close to the skull base.

The aim of this article is to provide Radiologists and Nuclear Medicine physicians the basic information required to understand how PET/MR scanners work, what are their limitations and how to evaluate their performance. It will cover the operational principles of standalone PET and MR imaging, as well as the technical challenges of creating a hybrid system and how they have been solved in the now commercially available scanners. Guidelines will be provided to interpret the main performance figures of hybrid PET/MR systems.

Attenuation correction (AC) for integrated PET/MR imaging in the human brain is still an open problem. In this study, we evaluated a simplified atlas-based AC (Atlas-AC) by comparing (18)F-FDG PET data corrected using either Atlas-AC or true CT data (CT-AC).We enrolled 8 patients (median age, 63 y). All patients underwent clinically indicated whole-body (18)F-FDG PET/CT for staging, restaging, or follow-up of malignant disease. All patients volunteered for an additional PET/MR of the head (additional tracer was not injected). For each patient, 2 AC maps were generated: an Atlas-AC map registered to a patient-specific liver accelerated volume acquisition-Flex MR sequence and using a vendor-provided head atlas generated from multiple CT head images and a CT-based AC map. For comparative AC, the CT-AC map generated from PET/CT was superimposed on the Atlas-AC map. PET images were reconstructed from the list-mode raw data from the PET/MR imaging scanner using each AC map. All PET images were normalized to the SPM5 PET template, and (18)F-FDG accumulation was quantified in 67 volumes of interest (VOIs; automated anatomic labeling atlas). Relative difference (%diff) between images based on Atlas-AC and CT-AC was calculated, and averaged difference images were generated. (18)F-FDG uptake in all VOIs was compared using Bland-Altman analysis.The range of error in all 536 VOIs was -3.0%-7.3%. Whole-brain (18)F-FDG uptake based on Atlas-AC was slightly underestimated (%diff = 2.19% ± 1.40%). The underestimation was most pronounced in the regions below the anterior/posterior commissure line, such as the cerebellum, temporal lobe, and central structures (%diff = 3.69% ± 1.43%, 3.25% ± 1.42%, and 3.05% ± 1.18%), suggesting that Atlas-AC tends to underestimate the attenuation values of the skull base bone.When compared with the gold-standard CT-AC, errors introduced using Atlas-AC did not exceed 8% in any brain region investigated. Underestimation of (18)F-FDG uptake was minor (4%) but significant in regions near the skull base.

Purpose: The purpose of this study was to compare only the performance of the PET component between a TOF-PET/CT (henceforth noted as PET/CT) scanner and an integrated TOF-PET/MRI (henceforth noted as PET/MRI) scanner concerning image quality parameters and quantification in terms of standardized uptake value (SUV) as a function of acquisition time (a surrogate of dose). The CT and MR image quality were not assessed, and that is beyond the scope of this study. Procedures: Five brain and five whole-body patients were included in the study. The PET/CT scan was used as a reference and the PET/MRI acquisition time was consecutively adjusted, taking into account the decay between the scans in order to expose both systems to the same amount of the emitted signal. The acquisition times were then retrospectively reduced to assess the performance of the PET/MRI for lower count rates. Image quality, image sharpness, artifacts, and noise were evaluated. SUV measurements were taken in the liver and in the white matter to compare quantification. Results: Quantitative evaluation showed strong correlation between PET/CT and PET/MRI brain SUVs. Liver correlation was good, however, with lower uptake estimation in PET/MRI, partially justified by bio-redistribution. The clinical evaluation showed that PET/MRI offers higher image quality and sharpness with lower levels of noise and artifacts compared to PET/CT with reduced acquisition times for whole-body scans while for brain scans there is no significant difference. Conclusion: The TOF-PET/MRI showed higher image quality compared to TOF-PET/CT as tested with reduced imaging times. However, this result accounts mainly for body imaging, while no significant differences were found in brain imaging.

Contains fulltext : 153443.PDF (Publisher’s version ) (Open Access) AIM: Aim of this study was to investigate the potential of 18F-FDG PET, diffusion weighted imaging (DWI) and susceptibility-weighted (T2*) MRI to predict response to systemic treatment in patients with colorectal liver metastases. The predictive values of pretreatment measurements and of early changes one week after start of therapy, were evaluated. METHODS: Imaging was performed prior to and one week after start of first line chemotherapy in 39 patients with colorectal liver metastases. 18F-FDG PET scans were performed on a PET/CT scanner and DWI and T2* were performed on a 1.5T MR scanner. The maximum standardized uptake values (SUV), total lesion glycolysis (TLG), apparent diffusion coefficient (ADC) and T2* value were assessed in the same lesions. Up to 5 liver metastases per patient were analyzed. Outcome measures were progression free survival (PFS), overall survival (OS) and size response. RESULTS: Pretreatment, high SUVmax, high TLG, low ADC and high T2* were associated with a shorter OS. Low pretreatment ADC value was associated with shorter PFS. After 1 week a significant drop in SUVmax and rise in ADC were observed. The drop in SUV was correlated with the rise in ADC (r=-0.58, p=0.002). Neither change in ADC nor in SUV was predictive of PFS or OS. T2* did not significantly change after start of treatment. CONCLUSION: Pretreatment SUVmax, TLG, ADC, and T2* values in colorectal liver metastases are predictive of patient outcome. Despite sensitivity of DWI and 18F-FDG PET for early treatment effects, change in these parameters was not predictive of long term outcome.

Objectives This study aimed to describe and evaluate the influence of time-of-flight (TOF) information on metal artifact reduction in positron emission tomography (PET) image quality in clinical simultaneous PET/magnetic resonance (MR) scanning. Materials and methods A total of 7 patients with various malignant tumors were included and underwent a PET/MR examination after standard PET/computed tomography. Baseline TOF and non-TOF PET images were reconstructed. Next, the TOF and non-TOF PET reconstructions were repeated after the introduction of artificial signal voids in the attenuation map to simulate metal artifacts of various sizes in a range of locations. Three different sizes of signal voids were inserted in the attenuation maps for each location of interest: over the maxilla, humeral head, chest, sternum, thoracic and lumbar spine, as well as the femoral head to replicate clinically relevant metal artifacts. The reconstructed images with the artifacts were then compared with the baseline reconstructed images. The mean percentage error in a region of interest surrounding the simulated artifact was used to compare between TOF and non-TOF images. Further comparison between TOF and non-TOF images was performed using histogram analysis. Results In all cases, the mean percentage error in a region of interest surrounding the simulated artifact was reduced when TOF information was included in the reconstruction. The inclusion of TOF also changes the distribution of smaller errors away from the origin of the artifact. In some anatomical regions, an increase in the number of small errors was noted with TOF, although the differences with non-TOF were minimal. Conclusions Positron emission tomographic imaging benefits from the integration of TOF information in simultaneous PET/MR. The inclusion of TOF information in simultaneous PET/MR imaging reduces errors related to metal artifacts at the site of the artifact.

Contains fulltext : 118299pub.pdf (Publisher’s version ) (Closed access) OBJECTIVES: Before diffusion-weighted imaging (DWI) can be implemented in standard clinical practice for response monitoring, data on reproducibility are needed to assess which differences outside the range of normal variation can be detected in an individual patient. In this study we assessed the reproducibility of the apparent diffusion coefficient (ADC) values in colorectal liver metastases. To provide a biological basis for these values, their relation with histopathology was assessed. METHODS: DWI was performed twice in 1 week in patients scheduled for metastasectomy of colorectal liver metastases. Correlation between ADC values and apoptosis marker p53, anti-apoptotic protein BCL-2, proliferation marker Ki67 and serum vascular endothelial growth factor (VEGF) concentration were assessed. RESULTS: A good reproducibility coefficient of the mean ADC (coefficient of reproducibility 0.20 x 10(-3) mm(2)/s) was observed in colorectal liver metastases (n = 21). The ADC value was related to the proliferation index and BCL-2 expression of the metastases. Furthermore, in metastases recently treated with systemic therapy, the ADC was significantly higher (1.27 x 10(-3) mm(2)/s vs 1.05 x 10(-3) mm(2)/s, P = 0.02). CONCLUSIONS: The good reproducibility, correlation with histopathology and implied sensitivity for systemic treatment-induced anti-tumour effects suggest that DWI might be an excellent tool to monitor response in metastatic colorectal cancer.

Background: The efficacy of anticancer therapy is usually evaluated by anatomical imaging. However, this method may be suboptimal for the evaluation of novel treatment modalities, such as targeted therapy. Theoretically, functional assessment of tumour response by diffusion weighted imaging (DWI) is an attractive tool for this purpose and may allow an early prediction of response. The optimal use of this method has still to be determined. Method: We reviewed the published literature on clinical DWI in the prediction of response to anticancer therapy, especially targeted therapy. Studies investigating the role of DWI in patients with cancer either for response prediction and/or response monitoring were selected for this analysis. Results: We identified 24 studies that met our criteria. Most studies showed a significant correlation between (changes in) apparent diffusion coefficient (ADC) values and treatment response. However, in different tumours and studies, both high and low pretreatment ADC were found to be associated with response rate. In the course of treatment, an increase in ADC was associated with response in most cases. Conclusion: The potential of DWI for (early) response monitoring of anticancer therapies has been demonstrated. However, validation is hampered by the lack of reproducibility and standardisation. We recommend that these issues should be properly addressed prior to further testing the clinical use of DWI in the assessment of treatments. (C) 2012 Elsevier Ireland Ltd. All rights reserved

Item does not contain fulltext INTRODUCTION: To understand which factors could affect the assessment of anti-vascular treatment by DCE-MRI, we investigated possible causes that could have hampered the selection of an optimal biological dose in humans of the vascular targeted agent NGR-hTNF by DCE-MRI: (1) insufficient reproducibility of DCE-MRI; (2) less specific targeting of NGR-hTNF; (3) interference of vessel characteristics with NGR-hTNF efficacy; (4) interfering pharmacodynamic effects. EXPERIMENTAL: In a phase I study NGR-hTNF, DCE-MRI was performed at baseline and 2h after NGR-hTNF administration in 31 patients with advanced solid cancer. Reproducibility measurements were performed in 5 other non-treated patients with metastatic disease. Mean k(ep), K(trans) values and their histogram distribution were determined in metastases and healthy liver tissue. The correlation between tumour size and DCE-MRI parameters was determined. Kinetics of soluble TNF receptors and the development of anti-TNF antibodies were assessed. RESULTS: Reproducibility of the DCE-MRI technique was adequate. Mean DCE-MRI parameters did not significantly change after NGR-hTNF administration, but histogram analyses showed significant changes in metastases and healthy liver tissue in some patients. The anti-vascular effects of NGR-hTNF were larger in smaller tumours, which have less mature neovasculature. Soluble TNF receptors were released. CONCLUSIONS: The difficulty to find an optimal biological dose of NGR-TNF by DCE-MRI is likely caused by a combination of factors: (i) different profiles of early anti-vascular effects in tumours and healthy liver tissue, (ii) dependence of the magnitude of the anti-vascular effect of NGR-hTNF on tumour size and (iii) shedding kinetics of soluble TNFalpha receptors.