Role of intravoxel incoherent motion parameters in gastroesophageal cancer: relationship with 18F-FDG-positron emission tomography, computed tomography perfusion and magnetic resonance perfusion imaging parameters.

BACKGROUND: 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. METHODS: 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: SUVmax, 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. RESULTS: IVIM and PET parameters showed significant negative correlations: MTV and bval (rs =-0.643, P=0.002), TLG and bval (rs=-0.699, P<0.01) and TLG and fp (rs=-0.577, P=0.006). Positive correlation was found for TLG and D (rs=0.705, P=0.000). Negative correlation was found for bval and staging (rs=0.590, P=0.005). Positive correlation was found for positive enhancement interval and BV (rs=0.547, P=0.007), BF and regression index (rs=0.753, P=0.005) and for time-to-peak and staging (rs=0.557, P=0.005). CONCLUSIONS: 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.

68Ga-PSMA-11 PET has the potential to improve patient selection for extended pelvic lymph node dissection in intermediate to high-risk prostate cancer.

INTRODUCTION: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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.

68Ga-PSMA-11 dose reduction for dedicated pelvic imaging with simultaneous PET/MR using TOF BSREM reconstructions.

OBJECTIVES: 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. METHODS: 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. RESULTS: Visually, TOF BSREM reconstructions with relatively high regularization parameter (ß) values are preferred. Quantitatively, however, high ß-values result in lower lesion maximum standardized uptake values (SUVmax) compared to the reference. A ß-value of 550 was considered the optimal compromise for the lowest possible 10% dose reconstructions, resulting in comparable visual assessment and lesion SUVmax. CONCLUSIONS: 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 ß = 550. This decreases the effective dose from 3.54 to 0.35 mSv. KEY POINTS: • Low-dose dedicated pelvic68Ga-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 pelvic68Ga-PSMA-11 PET/MR, new potential applications of68Ga-PSMA-11 PET for local staging or investigation of equivocal MRI findings could become applicable, even for patients without confirmed prostate cancer.

Levels of choline-containing compounds in normal liver and liver metastases of colorectal cancer as recorded by 1 H MRS.

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 cm3 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 cm3 ) 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 cm3 : 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.

Reduction of 18F-FDG Dose in Clinical PET/MR Imaging by Using Silicon Photomultiplier Detectors.

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.

WITHDRAWN: Evaluation of multifunctional imaging parameters in gastro-oesophageal cancer using F-18-FDG-PET/CT with integrated perfusion CT.

Ahead of Print article withdrawn by publisher.

Effect of Time-of-Flight Information on PET/MR Reconstruction Artifacts: Comparison of Free-breathing versus Breath-hold MR-based Attenuation Correction.

Purpose To evaluate the magnitude and anatomic extent of the artifacts introduced on positron emission tomographic (PET)/magnetic resonance (MR) images by respiratory state mismatch in the attenuation map. Materials and Methods The method was tested on 14 patients referred for an oncologic examination who underwent PET/MR imaging. The acquisition included standard PET and MR series for each patient, and an additional attenuation correction series was acquired by using breath hold. PET data were reconstructed with and without time-of-flight (TOF) information, first by using the standard free-breathing attenuation map and then again by using the additional breath-hold map. Two-tailed paired t testing and linear regression with 0 intercept was performed on TOF versus non-TOF and free-breathing versus breath-hold data for all detected lesions. Results Fluorodeoxyglucose-avid lesions were found in eight of the 14 patients included in the study. The uptake differences (maximum standardized uptake values) between PET reconstructions with free-breathing versus breath-hold attenuation ranged, for non-TOF reconstructions, from -18% to 26%. The corresponding TOF reconstructions yielded differences from -15% to 18%. Conclusion TOF information was shown to reduce the artifacts caused at PET/MR by respiratory mismatch between emission and attenuation data. © RSNA, 2016 Online supplemental material is available for this article.

Clinical evaluation of TOF versus non-TOF on PET artifacts in simultaneous PET/MR: a dual centre experience.

PURPOSE: 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. METHODS: 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). RESULTS: 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 < 0.01) indicating that artifacts were less noticeable when TOF information was included. CONCLUSION: Our study indicates that PET image artifacts are significantly mitigated with integration of TOF information in simultaneous PET/MR. The impact is predominantly seen in patients with significant artifacts due to metal implants.

Reduced respiratory motion artifacts using structural similarity in fast 2D dynamic contrast enhanced MRI of liver lesions.

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 < 0.05) and lower coefficient of repeatability of Ktrans in liver metastases compared with an analysis without correction. SSIM correction improves the reproducibility of the DCE-MRI parameter Ktrans in liver metastasis and reduces contamination of Ktrans values of lesions by that of surrounding normal liver tissue.

MR-based attenuation correction for cardiac FDG PET on a hybrid PET/MRI scanner: comparison with standard CT attenuation correction.

PURPOSE: The aim of this study was to evaluate the feasibility of attenuation correction (AC) for cardiac (18)F-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 < 0.0001) with narrow Bland-Altman limits of agreement (-8.5 to +12.6 %). Correlation coefficients were slightly lower between PET/CT and PET/MRI without TOF (n = 460 segments in 23 patients; r = 0.851; p < 0.0001) with broader Bland-Altman limits of agreement (-12.5 to +15.0 %). PET/MRI with and without TOF showed minimal underestimation of tracer uptake (-2.08 and -1.29 %, respectively), compared to PET/CT. CONCLUSION: Relative myocardial FDG uptake obtained from MR-based attenuation corrected FDG PET is highly comparable to standard CT-based attenuation corrected FDG PET, suggesting interchangeability of both AC techniques.

How does PET/MR work? Basic physics for physicians.

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.

Diffusion-weighted MR imaging in liver metastases of colorectal cancer: reproducibility and biological validation.

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 × 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 × 10(-3) mm(2)/s vs 1.05 × 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.

Reproducibility of Standardized Uptake Values Including Volume Metrics Between TOF-PET-MR and TOF-PET-CT.

Purpose: To investigate the reproducibility of tracer uptake measurements, including volume metrics, such as metabolic tumor volume (MTV) and tumor lesion glycolysis (TLG) obtained by TOF-PET-CT and TOF-PET-MR. Materials and Methods: Eighty consecutive patients with different oncologic diagnoses underwent TOF-PET-CT (Discovery 690; GE Healthcare) and TOF-PET-MR (SIGNA PET-MR; GE Healthcare) on the same day with single dose-18F-FDG injection. The scan order, PET-CT following or followed by PET-MR, was randomly assigned. A spherical volume of interest (VOI) of 30 mm was placed on the liver in accordance with the PERCIST criteria. For liver, the maximum and mean standard uptake value for body weight (SUV) and lean body mass (SUL) were obtained. For tumor delineation, VOI with a threshold of 40 and 50% of SUVmax was used (VOI40 and VOI50). The SUVmax, SUVmean, SUVpeak, MTV and TLG were calculated. The measurements were compared between the two scanners. Results: In total, 80 tumor lesions from 35 patients were evaluated. There was no statistical difference observed in liver regions, whereas in tumor lesions, SUVmax, SUV mean, and SUVpeak of PET-MR were significantly underestimated (p < 0.001) in both VOI40 and VOI50. Among volume metrics, there was no statistical difference observed except TLG on VOI50 (p = 0.03). Correlation between PET-CT and PET-MR of each metrics were calculated. There was a moderate correlation of the liver SUV and SUL metrics (r = 0.63-0.78). In tumor lesions, SUVmax and SUVmean had a stronger correlation with underestimation in PET-MR on VOI 40 (SUVmax and SUVmean; r = 0.92 and 0.91 with slope = 0.71 and 0.72, respectively). In the evaluation of MTV and TLG, the stronger correlations were observed both on VOI40 (MTV and TLG; r = 0.75 and 0.92) and VOI50 (MTV and TLG; r = 0.88 and 0.95) between PET-CT and PET-MR. Conclusion: PET metrics on TOF-PET-MR showed a good correlation with that of TOF-PET-CT. SUVmax and SUVpeak of tumor lesions were underestimated by 16% on PET-MRI. MTV with % threshold can be regarded as identical volumetric markers for both TOF-PET-CT and TOF-PET-MR.

Comparison of [18F]FDG PET/CT with magnetic resonance imaging for the assessment of human brown adipose tissue activity.

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 < 0.0001 and cohort 2: p = 0.0002). The FF of the supraclavicular adipose tissue depot was inversely related to its metabolic activity (SUVmean) in both cohorts (cohort 1: R2 = 0.18, p = 0.09 and cohort 2: R2 = 0.42, p = 0.009). CONCLUSION: MRI FF explains only about 40% of the variation in BAT glucose uptake. Thus, it can currently not be used to substitute [18F] FDG PET-based imaging for quantification of BAT activity. TRIAL REGISTRATION: ClinicalTrials.gov. NCT03189511 , registered on June 17, 2017, actual study start date was on May 31, 2017, retrospectively registered. NCT03269747 , registered on September 01, 2017.

Metal artifact reduction in 68Ga-PSMA-11 PET/MRI for prostate cancer patients with hip joint replacement using multiacquisition variable-resonance image combination.

BACKGROUND: PET/MRI has a high potential in oncology imaging, especially for tumor indications where high soft tissue contrast is crucial such as genitourinary tumors. One of the challenges for PET/MRI acquisition is handling of metal implants. In addition to conventional methods, more innovative techniques have been developed to reduce artifacts caused by those implants such as the selective multiacquisition variable-image combination (MAVRIC-SL). The aim of this study is to perform a quantitative and qualitative assessment of metal artifact reduction in 68Ga-PSMA-11 PET/MRI for prostate cancer patients with hip joint replacement using a selective MAVRIC-SL sequence for the whole pelvis. METHODS: We retrospectively analyzed data of 20 men with 37 metal hip implants diagnosed with PCA, staged or restaged by 68Ga-PSMA-11 PET/MRI from June 2016 to December 2017. Each signal cancellation per side or metal implant was analyzed on the reference sequence LAVA-FLEX, as well as T1-weighted fast spin echo (T1w-FSE) sequence and MAVRIC-SL. Two independent reviewers reported on a four-point scale whether abnormal pelvic 68Ga-PSMA-11 uptake could be assigned to an anatomical structure in the tested sequences. RESULTS: The smallest averaged signal void was observed on MAVRIC-SL sequences with a mean artifact size of 26.17 cm2 (range 12.63 to 42.93 cm2, p < 0.001). The best image quality regarding anatomical assignment of pathological PSMA uptakes in the pelvis by two independent readers was noted for MAVRIC-SL sequences, followed by T1w-FSE with excellent interreader agreement. CONCLUSIONS: MAVRIC-SL sequence allows better image quality in the surrounding of hip implants by reducing MR signal voids and increasing so the accuracy of anatomical assignment of pathological 68Ga-PSMA-11 uptake in the pelvis over LAVA-FLEX and T1w-FSE sequences.

The impact of atlas-based MR attenuation correction on the diagnosis of FDG-PET/MR for Alzheimer's diseases- A simulation study combining multi-center data and ADNI-data.

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.

Low-dose 18F-FDG TOF-PET/MR for accurate quantification of brown adipose tissue in healthy volunteers.

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.

68Ga-PSMA-11 PET/MR Detects Local Recurrence Occult on mpMRI in Prostate Cancer Patients After HIFU.

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.

Quantitative performance and optimal regularization parameter in block sequential regularized expectation maximization reconstructions in clinical 68Ga-PSMA PET/MR.

BACKGROUND: In contrast to ordered subset expectation maximization (OSEM), block sequential regularized expectation maximization (BSREM) positron emission tomography (PET) reconstruction algorithms can run until full convergence while controlling image quality and noise. Recent studies with BSREM and 18F-FDG PET reported higher signal-to-noise ratios and higher standardized uptake values (SUV). In this study, we investigate the optimal regularization parameter (ß) for clinical 68Ga-PSMA PET/MR reconstructions in the pelvic region applying time-of-flight (TOF) BSREM in comparison to TOF OSEM. Two-minute emission data from the pelvic region of 25 patients who underwent 68Ga-PSMA PET/MR were retrospectively reconstructed. Reference OSEM reconstructions had 28 subsets and 2 iterations. BSREM reconstructions were performed with 15 ß values between 150 and 1200. Regions of interest (ROIs) were drawn around lesions and in uniform background. Background SUVmean (average) and SUVstd (standard deviation), and lesion SUVmax (average of 5 hottest voxels) were calculated. Differences were analyzed using the Wilcoxon matched pairs signed-rank test. RESULTS: A total of 40 lesions were identified in the pelvic region. Background noise (SUVstd) and lesions SUVmax decreased with increasing ß. Image reconstructions with ß values lower than 400 have higher (p < 0.01) background noise, compared to the reference OSEM reconstructions, and are therefore less useful. Lesions with low activity on images reconstructed with ß values higher than 600 have a lower (p < 0.05) SUVmax compared to the reference. These reconstructions are likely visually appealing due to the lower background noise, but the lower SUVmax could possibly render small low-uptake lesions invisible. CONCLUSIONS: In our study, we showed that PET images reconstructed with TOF BSREM in combination with the 68Ga-PSMA tracer result in lower background noise and higher SUVmax values in lesions compared to TOF OSEM. Our study indicates that a ß value between 400 and 550 might be the optimal compromise between high SUVmax and low background noise.

Correction to: impact of time-of-flight PET on quantification accuracy and lesion detection in simultaneous 18F-choline PET/MRI for prostate cancer.

Unfortunately, after publication of this article [1], it was noticed that the name of Urs J. Muehlematter was incorrectly displayed as Urs J. Mühlematter. The corrected author list can be seen above and the original article has been corrected to reflect this.