A PET/MRI study on the effect of obesity and NAFLD on hepatic [18F]FDG uptake.

PURPOSE: The potential limitations of hepatic [18F]FDG-PET imaging for individuals with obesity and excessive liver fat (NAFLD) are being investigated. In this study, we aim to determine the reliability of standardized uptake values (SUVs) focusing on adjustment for liver fat content (LFC) derived from DIXON images and the effects of whole-body normalizations. METHODS: Lean and with obesity volunteers who underwent [18F]FDG-PET/MRI were reviewed retrospectively. DIXON fat images were used to determine LFC and for adjustment of SUVmean. The hepatic SUVs (mean, fat adjusted mean and max) were normalized to body weight, lean body mass and body surface area. Blood samples were analysed for glucose, serological liver enzymes and lipoproteins for further correlation of [18F]FDG uptake. RESULTS: Out of 11 volunteers with obesity (M:8, F:3, BMI:30-39 kg/m2), 9 confirmed the presence of NAFLD (>5.6 % fat). 22 age-matched lean volunteers (M:10, F:11, BMI:19-26 kg/m2) were used as control group. Both SUVmean, before and after adjustment to LFC, did not provide any difference between lean and with obesity groups under BW, LBM and BSA. SUVmax BW showed a difference between groups (p = 0.05). SUVs were independent of levels of GPT, GOT, gGT, insulin, HOMA-IR, triglycerides, cholesterol and LDL. Volunteers with low HDL were clustered with an increased hepatic [18F]FDG uptake. CONCLUSION: Our method for adjustment of hepatic [18F]FDG-PET with DIXON fat images allows to achieve accurate results for individuals with NAFLD and obesity. For homogenic results, raw SUVmean should be combined with adjustment for liver fat, appropriate normalization and consideration of HDL levels.

In vivo assessment of safety, biodistribution, and radiation dosimetry of the [18F]Me4FDG PET-radiotracer in adults.

BACKGROUND: Approaches targeting the sodium-glucose cotransporter (SGLT) could represent a promising future therapeutic strategy for numerous oncological and metabolic diseases. In this study, we evaluated the safety, biodistribution and radiation dosimetry of the glucose analogue positron emission tomography (PET) agent [18F] labeled alpha-methyl-4-deoxy-4-[18F]fluoro-D-glucopyranoside ([18F]Me4FDG) with high sodium-glucose cotransporter and low glucose transporter (GLUT) affinity. For this purpose, five healthy volunteers (1 man, 4 women) underwent multiple whole-body PET/computed tomography (CT) examinations starting with injection and up to 4 h after injection of averaged (2.4 ± 0.1) MBq/kg (range: 2.3-2.5 MBq/kg) administered activity. The PET/CT scans were conducted in 5 separate sessions, blood pressure and temperature were measured, and blood and urine samples were collected before the scans and one hour after injection to assess toxicity. Measurements of [18F]Me4FDG radioactivity in organs of interest were determined from the PET/CT scans at 5 time points. Internal dosimetry was performed on voxel level using a fast Monte Carlo approach. RESULTS: All studied volunteers could well tolerate the [18F]Me4FDG and no adverse event was reported. The calculated effective dose was (0.013 ± 0.003) mSv/MBq. The organs with the highest absorbed dose were the kidneys with 0.05 mSv/MBq per kidney. The brain showed almost no uptake. After 60 min, (12 ± 15) % of the administered dose was excreted into the bladder. CONCLUSION: Featuring an effective dose of only 0.013 ± 0.003 mSv/MBq and no occurrence of side effects, the glucose analogue [18F]Me4FDG seems to be a safe radio-tracer with a favorable biodistribution for PET imaging and also within several consecutive scans. TRIAL REGISTRATION NUMBER: NCT03557138, Registered 22 February 2017, https://ichgcp.net/clinical-trials-registry/NCT03557138 .

St. John's wort extract with a high hyperforin content does not induce P-glycoprotein activity at the human blood-brain barrier.

St. John's wort (SJW) extract, a herbal medicine with antidepressant effects, is a potent inducer of intestinal and/or hepatic cytochrome P450 (CYP) enzymes and P-glycoprotein (P-gp), which can cause clinically relevant drug interactions. It is currently not known whether SJW can also induce P-gp activity at the human blood-brain barrier (BBB), which may potentially lead to decreased brain exposure and efficacy of certain central nervous system (CNS)-targeted P-gp substrate drugs. In this study, we used a combination of positron emission tomography (PET) imaging and cocktail phenotyping to gain a comprehensive picture on the effect of SJW on central and peripheral P-gp and CYP activities. Before and after treatment of healthy volunteers (n = 10) with SJW extract with a high hyperforin content (3-6%) for 12-19 days (1800 mg/day), the activity of P-gp at the BBB was assessed by means of PET imaging with the P-gp substrate [11C]metoclopramide and the activity of peripheral P-gp and CYPs was assessed by administering a low-dose phenotyping cocktail (caffeine, omeprazole, dextromethorphan, and midazolam or fexofenadine). SJW significantly increased peripheral P-gp, CYP3A, and CYP2C19 activity. Conversely, no significant changes in the peripheral metabolism, brain distribution, and P-gp-mediated efflux of [11C]metoclopramide across the BBB were observed following the treatment with SJW extract. Our data suggest that SJW does not lead to significant P-gp induction at the human BBB despite its ability to induce peripheral P-gp and CYPs. Simultaneous intake of SJW with CNS-targeted P-gp substrate drugs is not expected to lead to P-gp-mediated drug interactions at the BBB.

Direct Patlak Reconstruction of [68Ga]Ga-PSMA PET for the Evaluation of Primary Prostate Cancer Prior Total Prostatectomy: Results of a Pilot Study.

To investigate the use of kinetic parameters derived from direct Patlak reconstructions of [68Ga]Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) to predict the histological grade of malignancy of the primary tumor of patients with prostate cancer (PCa). Thirteen patients (mean age 66 ± 10 years) with a primary, therapy-naïve PCa (median PSA 9.3 [range: 6.3-130 µg/L]) prior radical prostatectomy, were recruited in this exploratory prospective study. A dynamic whole-body [68Ga]Ga-PSMA-11 PET/CT scan was performed for all patients. Measured quantification parameters included Patlak slope (Ki: absolute rate of tracer consumption) and Patlak intercept (Vb: degree of tracer perfusion in the tumor). Additionally, the mean and maximum standardized uptake values (SUVmean and SUVmax) of the tumor were determined from a static PET 60 min post tracer injection. In every patient, initial PSA (iPSA) values that were also the PSA level at the time of the examination and final histology results with Gleason score (GS) grading were correlated with the quantitative readouts. Collectively, 20 individual malignant prostate lesions were ascertained and histologically graded for GS with ISUP classification. Six lesions were classified as ISUP 5, two as ISUP 4, eight as ISUP 3, and four as ISUP 2. In both static and dynamic PET/CT imaging, the prostate lesions could be visually distinguished from the background. The average values of the SUVmean, slope, and intercept of the background were 2.4 (±0.4), 0.015 1/min (±0.006), and 52% (±12), respectively. These were significantly lower than the corresponding parameters extracted from the prostate lesions (all p < 0.01). No significant differences were found between these values and the various GS and ISUP (all p > 0.05). Spearman correlation coefficient analysis demonstrated a strong correlation between static and dynamic PET/CT parameters (all r ≥ 0.70, p < 0.01). Both GS and ISUP grading revealed only weak correlations with the mean and maximum SUV and tumor-to-background ratio derived from static images and dynamic Patlak slope. The iPSA demonstrated no significant correlation with GS and ISUP grading or with dynamic and static PET parameter values. In this cohort of mainly high-risk PCa, no significant correlation between [68Ga]Ga-PSMA-11 perfusion and consumption and the aggressiveness of the primary tumor was observed. This suggests that the association between SUV values and GS may be more distinctive when distinguishing clinically relevant from clinically non-relevant PCa.

Evaluation of Gliomas with Magnetic Resonance Fingerprinting with PET Correlation-A Comparative Study.

OBJECTIVES: Advanced MR imaging of brain tumors is still mainly based on qualitative imaging. PET imaging offers additive metabolic information, and MR fingerprinting (MRF) offers a novel approach to quantitative data acquisition. The purpose of this study was to evaluate the ability of MRF to predict tumor regions and grading in combination with PET. METHODS: Seventeen patients with histologically verified infiltrating gliomas and available amino-acid PET data were enrolled. ROIs for solid tumor parts (SPo), perifocal edema (ED1), and normal-appearing white matter (NAWM) were selected on conventional MRI sequences and aligned to the MRF and PET images. The predictability of gliomas by region and grading as well as intermodal correlations were assessed. RESULTS: For MRF, we calculated an overall predictability by region (SPo, ED1, and NAWM) for all of the MRF parameters of 76.5%, 47.1%, and 94.1%, respectively. The overall ability to distinguish low- from high-grade gliomas using MRF was 88.9% for LGG and 75% for HGG, with an accuracy of 82.4%, a ppV of 85.71%, and an npV of 80%. PET positivity was found in 13/17 patients for solid tumor parts, and in 3/17 patients for the edema region. However, there was no significant difference in region-specific MRF values between PET positive and PET negative patients. CONCLUSIONS: MRF and PET provide quantitative measurements of the tumor tissue characteristics of gliomas, with good predictability. Nonetheless, the results are dissimilar, reflecting the different underlying mechanisms of each method.

Characterization of the partial volume effect along the axial field-of-view of the Biograph Vision Quadra total-body PET/CT system for multiple isotopes.

BACKGROUND: Total-body PET scanners with axial field of views (FOVs) longer than 1 m enable new applications to study multiple organs (e.g., the brain-gut-axis) simultaneously. As the spatial resolution and the associated partial volume effect (PVE) can vary significantly along the FOV, detailed knowledge of the contrast recovery coefficients (CRCs) is a prerequisite for image analysis and interpretation of quantitative results. The aim of this study was to determine the CRCs, as well as voxel noise, for multiple isotopes throughout the 1.06 m axial FOV of the Biograph Vision Quadra PET/CT system (Siemens Healthineers). MATERIALS AND METHODS: Cylindrical phantoms equipped with three different sphere sizes (inner diameters 7.86 mm, 28 and 37 mm) were utilized for the PVE evaluation. The 7.86 mm sphere was filled with F-18 (8:1 and 4:1), Ga-68 (8:1) and Zr-89 (8:1). The 28 mm and 37 mm spheres were filled with F-18 (8:1). Background concentration in the respective phantoms was of ~ 3 kBq/ml. The phantoms were measured at multiple positions in the FOV (axial: 0, 10, 20, 30, 40 and 50 cm, transaxial: 0, 10, 20 cm). The data were reconstructed with the standard clinical protocol, including PSF correction and TOF information with up to 10 iterations for maximum ring differences (MRDs) of 85 and 322; CRCs, as well as voxel noise levels, were determined for each position. RESULTS: F-18 CRCs (SBR 8:1 and 4:1) of the 7.86 mm sphere decreased up to 18% from the center FOV (cFOV) toward the transaxial edge and increased up to 17% toward the axial edge. Noise levels were below 15% for the default clinical reconstruction parameters. The larger spheres exhibited a similar pattern. Zr-89 revealed ~ 10% lower CRCs than F-18 but larger noise (9.1% (F-18), 19.1% (Zr-89); iteration 4, cFOV) for the default reconstruction. Zr-89 noise levels in the cFOV significantly decreased (~ 28%) when reconstructing the data with MRD322 compared with MRD85 along with a slight decrease in CRC values. Ga-68 exhibited the lowest CRCs for the three isotopes and noise characteristics comparable to those of F-18. CONCLUSIONS: Distinct differences in the PVE within the FOV were detected for clinically relevant isotopes F-18, Ga-68 and Zr-89, as well as for different sphere sizes. Depending on the positions inside the FOV, the sphere-to-background ratios, count statistics and isotope used, this can result in an up to 50% difference between CRCs. Hence, these changes in PVE can significantly affect the quantitative analysis of patient data. MRD322 resulted in slightly lower CRC values, especially in the center FOV, whereas the voxel noise significantly decreased compared with MRD85.

Comparison of cardiac image-derived input functions for quantitative whole body [18F]FDG imaging with arterial blood sampling.

Introduction: Dynamic positron emission tomography (PET) and the application of kinetic models can provide important quantitative information based on its temporal information. This however requires arterial blood sampling, which can be challenging to acquire. Nowadays, state-of-the-art PET/CT systems offer fully automated, whole-body (WB) kinetic modelling protocols using image-derived input functions (IDIF) to replace arterial blood sampling. Here, we compared the validity of an automatic WB kinetic model protocol to the reference standard arterial input function (AIF) for both clinical and research settings. Methods: Sixteen healthy participants underwent dynamic WB [18F]FDG scans using a continuous bed motion PET/CT system with simultaneous arterial blood sampling. Multiple processing pipelines that included automatic and manually generated IDIFs derived from the aorta and left ventricle, with and without motion correction were compared to the AIF. Subsequently generated quantitative images of glucose metabolism were compared to evaluate performance of the different input functions. Results: We observed moderate to high correlations between IDIFs and the AIF regarding area under the curve (r = 0.49-0.89) as well as for the cerebral metabolic rate of glucose (CMRGlu) (r = 0.68-0.95). Manual placing of IDIFs and motion correction further improved their similarity to the AIF. Discussion: In general, the automatic vendor protocol is a feasible approach for the quantification of CMRGlu for both, clinical and research settings where expertise or time is not available. However, we advise on a rigorous inspection of the placement of the volume of interest, the resulting IDIF, and the quantitative values to ensure valid interpretations. In protocols requiring longer scan times or where cohorts are prone to involuntary movement, manual IDIF definition with additional motion correction is recommended, as this has greater accuracy and reliability.

Whole-body metabolic connectivity framework with functional PET.

The nervous and circulatory system interconnects the various organs of the human body, building hierarchically organized subsystems, enabling fine-tuned, metabolically expensive brain-body and inter-organ crosstalk to appropriately adapt to internal and external demands. A deviation or failure in the function of a single organ or subsystem could trigger unforeseen biases or dysfunctions of the entire network, leading to maladaptive physiological or psychological responses. Therefore, quantifying these networks in healthy individuals and patients may help further our understanding of complex disorders involving body-brain crosstalk. Here we present a generalized framework to automatically estimate metabolic inter-organ connectivity utilizing whole-body functional positron emission tomography (fPET). The developed framework was applied to 16 healthy subjects (mean age ± SD, 25 ± 6 years; 13 female) that underwent one dynamic 18F-FDG PET/CT scan. Multiple procedures of organ segmentation (manual, automatic, circular volumes) and connectivity estimation (polynomial fitting, spatiotemporal filtering, covariance matrices) were compared to provide an optimized thorough overview of the workflow. The proposed approach was able to estimate the metabolic connectivity patterns within brain regions and organs as well as their interactions. Automated organ delineation, but not simplified circular volumes, showed high agreement with manual delineation. Polynomial fitting yielded similar connectivity as spatiotemporal filtering at the individual subject level. Furthermore, connectivity measures and group-level covariance matrices did not match. The strongest brain-body connectivity was observed for the liver and kidneys. The proposed framework offers novel opportunities towards analyzing metabolic function from a systemic, hierarchical perspective in a multitude of physiological pathological states.

Feasibility of dose reduction for [18F]FDG-PET/MR imaging of patients with non-lesional epilepsy.

The aim of the study was to evaluate the effect of reduced injected [18F]FDG activity levels on the quantitative and diagnostic accuracy of PET images of patients with non-lesional epilepsy (NLE).Nine healthy volunteers and nine patients with NLE underwent 60-min dynamic list-mode (LM) scans on a fully-integrated PET/MRI system. Injected FDG activity levels were reduced virtually by randomly removing counts from the last 10-min of the LM data, so as to simulate the following activity levels: 50 %, 35 %, 20 %, and 10 % of the original activity. Four image reconstructions were evaluated: standard OSEM, OSEM with resolution recovery (PSF), the A-MAP, and the Asymmetrical Bowsher (AsymBowsher) algorithms. For the A-MAP algorithms, two weights were selected (low and high). Image contrast and noise levels were evaluated for all subjects while the lesion-to-background ratio (L/B) was only evaluated for patients. Patient images were scored by a Nuclear Medicine physician on a 5-point scale to assess clinical impression associated with the various reconstruction algorithms.The image contrast and L/B ratio characterizing all four reconstruction algorithms were similar, except for reconstructions based on only 10 % of total counts. Based on clinical impression, images with diagnostic quality can be achieved with as low as 35 % of the standard injected activity. The selection of algorithms utilizing an anatomical prior did not provide a significant advantage for clinical readings, despite a small improvement in L/B (< 5 %) using the A-MAP and AsymBowsher reconstruction algorithms.In patients with NLE who are undergoing [18F]FDG-PET/MR imaging, the injected [18F]FDG activity can be reduced to 35 % of the original dose levels without compromising.

Sex-specific radiomic features of L-[S-methyl-11C] methionine PET in patients with newly-diagnosed gliomas in relation to IDH1 predictability.

Introduction: Amino-acid positron emission tomography (PET) is a validated metabolic imaging approach for the diagnostic work-up of gliomas. This study aimed to evaluate sex-specific radiomic characteristics of L-[S-methyl-11Cmethionine (MET)-PET images of glioma patients in consideration of the prognostically relevant biomarker isocitrate dehydrogenase (IDH) mutation status. Methods: MET-PET of 35 astrocytic gliomas (13 females, mean age 41 ± 13 yrs. and 22 males, mean age 46 ± 17 yrs.) and known IDH mutation status were included. All patients underwent radiomic analysis following imaging biomarker standardization initiative (IBSI)-conform guidelines both from standardized uptake value (SUV) and tumor-to-background ratio (TBR) PET values. Aligned Monte Carlo (MC) 100-fold split was utilized for SUV and TBR dataset pairs for both sex and IDH-specific analysis. Borderline and outlier scores were calculated for both sex and IDH-specific MC folds. Feature ranking was performed by R-squared ranking and Mann-Whitney U-test together with Bonferroni correction. Correlation of SUV and TBR radiomics in relation to IDH mutational status in male and female patients were also investigated. Results: There were no significant features in either SUV or TBR radiomics to distinguish female and male patients. In contrast, intensity histogram coefficient of variation (ih.cov) and intensity skewness (stat.skew) were identified as significant to predict IDH +/-. In addition, IDH+ females had significant ih.cov deviation (0.031) and mean stat.skew (-0.327) differences compared to IDH+ male patients (0.068 and -0.123, respectively) with two-times higher standard deviations of the normal brain background MET uptake as well. Discussion: We demonstrated that female and male glioma patients have significantly different radiomic profiles in MET PET imaging data. Future IDH prediction models shall not be built on mixed female-male cohorts, but shall rely on sex-specific cohorts and radiomic imaging biomarkers.

EFOMP's protocol quality controls in PET/CT and PET/MR.

This article presents the protocol on Quality Controls in PET/CT and PET/MRI published online in May 2022 by the European Federation of Organisations for Medical Physics (EFOMP), which was developed by the Working group for PET/CT and PET/MRI Quality Control (QC) protocol. The main objective of this protocol was to comprehensively provide simple and practical procedures that may be integrated into clinical practice to identify changes in the PET/CT/MRI system's performance and avoid short- and long-term quality deterioration. The protocol describes the quality control procedures on radionuclide calibrators, weighing scales, PET, CT and MRI systems using selected and measurable parameters that are directly linked to clinical images quality. It helps to detect problems before they can impact clinical studies in terms of safety, image quality, quantification accuracy and patient radiation dose. CT and MRI QCs are described only in the context of their use for PET (attenuation correction and anatomical localization) imaging. Detailed step-by-step instructions have been provided, limiting any misinterpretations or interpersonal variations as much as possible. This paper presents the main characteristics of the protocol illustrated together with a brief summary of the content of each chapter. A regular QC based on the proposed protocol would guarantee that PET/CT and PET/MRI systems operate under optimal conditions, resulting in the best performance for routine clinical tasks.

Image quality assessment along the one metre axial field-of-view of the total-body Biograph Vision Quadra PET/CT system for 18F-FDG.

AIM: Recently, total-body PET/CT systems with an extended axial field-of-view (aFOV) became commercially available which allow acquiring physiologic information of multiple organs simultaneously. However, the nominal aFOV may clinically not be used effectively due to the inherently reduced sensitivity at the distal ends of the aFOV. The aim of this study was to assess the extent of the useful aFOV of the Biograph Vision Quadra PET/CT system. METHODS: A NEMA image quality (IQ) phantom mimicking a standard [18F]FDG examination was used. Image contrast and noise were assessed across the 106 cm aFOV of the Biograph Vision Quadra PET/CT system (Siemens Healthineers). Phantom acquisitions were performed at different axial positions. PET data were rebinned to simulate different acquisition times for a standard injected activity and reconstructed using different filter settings to evaluate the noise and images along the axial direction. RESULTS: Image noise and contrast were stable within the central 80 cm of the aFOV. Outside this central area, image contrast variability as well as image noise increased. This degradation of IQ was in particular evident for short acquisition times of less than 30 s. At 10 min acquisition time and in the absence of post-reconstruction filtering, the useful aFOV was 100 cm. For a 2 min acquisition time, a useful aFOV with image noise below 15% was only achievable using Gaussian filtering with axial extents of between 83 and 103 cm when going from 2 to 6 mm full-width-half-maximum, respectively. CONCLUSION: Image noise increases substantially towards the ends of the aFOV. However, good IQ in compliance with generally accepted benchmarks is achievable for an aFOV of > 90 cm. When accepting higher image noise or using dedicated protocol settings such as stronger filtering a useful aFOV of around 1 m can be achieved for a 2 min acquisition time.

Impact of SSTR PET on Inter-Observer Variability of Target Delineation of Meningioma and the Possibility of Using Threshold-Based Segmentations in Radiation Oncology.

Aim: The aim of this study was to assess the effects of including somatostatin receptor agonist (SSTR) PET imaging in meningioma radiotherapy planning by means of changes in inter-observer variability (IOV). Further, the possibility of using threshold-based delineation approaches for semiautomatic tumor volume definition was assessed. Patients and Methods: Sixteen patients with meningioma undergoing fractionated radiotherapy were delineated by five radiation oncologists. IOV was calculated by comparing each delineation to a consensus delineation, based on the simultaneous truth and performance level estimation (STAPLE) algorithm. The consensus delineation was used to adapt a threshold-based delineation, based on a maximization of the mean Dice coefficient. To test the threshold-based approach, seven patients with SSTR-positive meningioma were additionally evaluated as a validation group. Results: The average Dice coefficients for delineations based on MRI alone was 0.84 ± 0.12. For delineation based on MRI + PET, a significantly higher dice coefficient of 0.87 ± 0.08 was found (p < 0.001). The Hausdorff distance decreased from 10.96 ± 11.98 mm to 8.83 ± 12.21 mm (p < 0.001) when adding PET for the lesion delineation. The best threshold value for a threshold-based delineation was found to be 14.0% of the SUVmax, with an average Dice coefficient of 0.50 ± 0.19 compared to the consensus delineation. In the validation cohort, a Dice coefficient of 0.56 ± 0.29 and a Hausdorff coefficient of 27.15 ± 21.54 mm were found for the threshold-based approach. Conclusions: SSTR-PET added to standard imaging with CT and MRI reduces the IOV in radiotherapy planning for patients with meningioma. When using a threshold-based approach for PET-based delineation of meningioma, a relatively low threshold of 14.0% of the SUVmax was found to provide the best agreement with a consensus delineation.

Positron range in combination with point-spread-function correction: an evaluation of different implementations for [124I]-PET imaging.

AIM: To evaluate the effect of combining positron range correction (PRC) with point-spread-function (PSF) correction and to compare different methods of implementation into iterative image reconstruction for 124I-PET imaging. MATERIALS AND METHODS: Uniform PR blurring kernels of 124I were generated using the GATE (GEANT4) framework in various material environments (lung, water, and bone) and matched to a 3D matrix. The kernels size was set to 11 × 11 × 11 based on the maximum PR in water and the voxel size of the PET system. PET image reconstruction was performed using the standard OSEM algorithm, OSEM with PRC implemented before the forward projection (OSEM+PRC simplified) and OSEM with PRC implemented in both forward- and back-projection steps (full implementation) (OSEM+PRC). Reconstructions were repeated with resolution recovery, point-spread function (PSF) included. The methods and kernel variation were validated using different phantoms filled with 124I acquired on a Siemens mCT PET/CT system. The data was evaluated for contrast recovery and image noise. RESULTS: Contrast recovery improved by 2-10% and 4-37% with OSEM+PRC simplified and OSEM+PRC, respectively, depending on the sphere size of the NEMA IQ phantom. Including PSF in the reconstructions further improved contrast by 4-19% and 3-16% with the PSF+PRC simplified and PSF+PRC, respectively. The benefit of PRC was more pronounced within low-density material. OSEM-PRC and OSEM-PSF as well as OSEM-PSF+PRC in its full- and simplified implementation showed comparable noise and convergence. OSEM-PRC simplified showed comparably faster convergence but at the cost of increased image noise. CONCLUSIONS: The combination of the PSF and PRC leads to increased contrast recovery with reduced image noise compared to stand-alone PSF or PRC reconstruction. For OSEM-PRC reconstructions, a full implementation in the reconstruction is necessary to handle image noise. For the combination of PRC with PSF, a simplified PRC implementation can be used to reduce reconstruction times.

Biodistribution and dosimetry of the GluN2B-specific NMDA receptor PET radioligand (R)-[11C]Me-NB1.

BACKGROUND: The NMDA receptor (NMDAR) plays a key role in the central nervous system, e.g., for synaptic transmission. While synaptic NMDARs are thought to have protective characteristics, activation of extrasynaptic NMDARs might trigger excitotoxic processes linked to neuropsychiatric disorders. Since extrasynaptic NMDARs are typically GluN2B-enriched, the subunit is an interesting target for drug development and treatment monitoring. Recently, the novel GluN2B-specific PET radioligand (R)-[11C]Me-NB1 was investigated in rodents and for the first time successfully translated to humans. To assess whether (R)-[11C]Me-NB1 is a valuable radioligand for (repeated) clinical applications, we evaluated its safety, biodistribution and dosimetry. METHODS: Four healthy subjects (two females, two males) underwent one whole-body PET/MR measurement lasting for more than 120 min. The GluN2B-specific radioligand (R)-[11C]Me-NB1 was administered simultaneously with the PET start. Subjects were measured in nine passes and six bed positions from head to mid-thigh. Regions of interest was anatomically defined for the brain, thyroid, lungs, heart wall, spleen, stomach contents, pancreas, liver, kidneys, bone marrow and urinary bladder contents, using both PET and MR images. Time-integrated activity coefficients were estimated to calculate organ equivalent dose coefficients and the effective dose coefficient. Additionally, standardized uptake values (SUV) were computed to visualize the biodistribution. RESULTS: Administration of the radioligand was safe without adverse events. The organs with the highest uptake were the urinary bladder, spleen and pancreas. Organ equivalent dose coefficients were higher in female in almost all organs, except for the urinary bladder of male. The effective dose coefficient was 6.0 µSv/MBq. CONCLUSION: The GluN2B-specific radioligand (R)-[11C]Me-NB1 was well-tolerated without reported side effects. Effective dose was estimated to 1.8 mSv when using 300 MBq of presented radioligand. The critical organ was the urinary bladder. Due to the low effective dose coefficient of this radioligand, longitudinal studies for drug development and treatment monitoring of neuropsychiatric disorders including neurodegenerative diseases are possible. Trial registration Registered on 11th of June 2019 at https://www.basg.gv.at (EudraCT: 2018-002933-39).

A multi-modality physical phantom for mimicking tumor heterogeneity patterns in PET/CT and PET/MRI.

BACKGROUND: Hybrid imaging (e.g., positron emission tomography [PET]/computed tomography [CT], PET/magnetic resonance imaging [MRI]) helps one to visualize and quantify morphological and physiological tumor characteristics in a single study. The noninvasive characterization of tumor heterogeneity is essential for grading, treatment planning, and following-up oncological patients. However, conventional (CONV) image-based parameters, such as tumor diameter, tumor volume, and radiotracer activity uptake, are insufficient to describe tumor heterogeneities. Here, radiomics shows promise for a better characterization of tumors. Nevertheless, the validation of such methods demands imaging objects capable of reflecting heterogeneities in multi-modality imaging. We propose a phantom to simulate tumor heterogeneity repeatably in PET, CT, and MRI. METHODS: The phantom consists of three 50-ml plastic tubes filled partially with acrylic spheres of S1: 1.6 mm, S2: 50%(1.6 mm)/50%(6.3 mm), or S3: 6.3-mm diameter. The spheres were fixed to the bottom of each tube by a plastic grid, yielding one sphere free homogeneous region and one heterogeneous (S1, S2, or S3) region per tube. A 3-tube phantom and its replica were filled with a fluorodeoxyglucose (18F) solution for test-retest measurements in a PET/CT Siemens TPTV and a PET/MR Siemens Biograph mMR system. A number of 42 radiomic features (10 first order and 32 texture features) were calculated for each phantom region and imaging modality. Radiomic features stability was evaluated through coefficients of variation (COV) across phantoms and scans for PET, CT, and MRI. Further, the Wilcoxon test was used to assess the capability of stable features to discriminate the simulated phantom regions. RESULTS: The different patterns (S1-S3) did present visible heterogeneity in all imaging modalities. However, only for CT and MRI, a clear visual difference was present between the different patterns. Across all phantom regions in PET, CT, and MR images, 10, 16, and 21 features out of 42 evaluated features in total had a COV of 10% or less. In particular, CONV, histogram, and gray-level run length matrix features showed high repeatability for all the phantom regions and imaging modalities. Several of repeatable texture features allowed the image-based discrimination of the different phantom regions (p < 0.05). However, depending on the feature, different pattern discrimination capabilities were found for the different imaging modalities. CONCLUSION: The proposed phantom appears suitable for simulating heterogeneities in PET, CT, and MRI. We demonstrate that it is possible to select radiomic features for the readout of the phantom. Most of these features had been shown to be relevant in previous clinical studies.

7T HR FID-MRSI Compared to Amino Acid PET: Glutamine and Glycine as Promising Biomarkers in Brain Tumors.

(1) Background: Recent developments in 7T magnetic resonance spectroscopic imaging (MRSI) made the acquisition of high-resolution metabolic images in clinically feasible measurement times possible. The amino acids glutamine (Gln) and glycine (Gly) were identified as potential neuro-oncological markers of importance. For the first time, we compared 7T MRSI to amino acid PET in a cohort of glioma patients. (2) Methods: In 24 patients, we co-registered 7T MRSI and routine PET and compared hotspot volumes of interest (VOI). We evaluated dice similarity coefficients (DSC), volume, center of intensity distance (CoI), median and threshold values for VOIs of PET and ratios of total choline (tCho), Gln, Gly, myo-inositol (Ins) to total N-acetylaspartate (tNAA) or total creatine (tCr). (3) Results: We found that Gln and Gly ratios generally resulted in a higher correspondence to PET than tCho. Using cutoffs of 1.6-times median values of a control region, DSCs to PET were 0.53 ± 0.36 for tCho/tNAA, 0.66 ± 0.40 for Gln/tNAA, 0.57 ± 0.36 for Gly/tNAA, and 0.38 ± 0.31 for Ins/tNAA. (4) Conclusions: Our 7T MRSI data corresponded better to PET than previous studies at lower fields. Our results for Gln and Gly highlight the importance of future research (e.g., using Gln PET tracers) into the role of both amino acids.

Additively manufactured, solid object structures for adjustable image contrast in Magnetic Resonance Imaging.

The choice of materials challenges the development of Magnetic Resonance Imaging (MRI) phantoms and, to date, is mainly limited to water-filled compartments or gel-based components. Recently, solid materials have been introduced through additive manufacturing (AM) to mimic complex geometrical structures. Nonetheless, no such manufactured solid materials are available with controllable MRI contrast to mimic organ substructures or lesion heterogeneities. Here, we present a novel AM design that allows MRI contrast manipulation by varying the partial volume contribution to a ROI/voxel of MRI-visible material within an imaging object. Two sets of 11 cubes and three replicates of a spherical tumour model were designed and printed using AM. Most samples presented varying MRI-contrast in standard MRI sequences, based mainly on spin density and partial volume signal variation. A smooth and continuous MRI-contrast gradient could be generated in a single-compartment tumour model. This concept supports the development of more complex MRI phantoms that mimic the appearance of heterogeneous tumour tissues.

Implementation of a Spatially-Variant and Tissue-Dependent Positron Range Correction for PET/CT Imaging.

Aim: To develop and evaluate a new approach for spatially variant and tissue-dependent positron range (PR) correction (PRC) during the iterative PET image reconstruction. Materials and Methods: The PR distributions of three radionuclides (18F, 68Ga, and 124I) were simulated using the GATE (GEANT4) framework in different material compositions (lung, water, and bone). For every radionuclide, the uniform PR kernel was created by mapping the simulated 3D PR point cloud to a 3D matrix with its size defined by the maximum PR in lung (18F) or water (68Ga and 124I) and the PET voxel size. The spatially variant kernels were composed from the uniform PR kernels by analyzing the material composition of the surrounding medium for each voxel before implementation as tissue-dependent, point-spread functions into the iterative image reconstruction. The proposed PRC method was evaluated using the NEMA image quality phantom (18F, 68Ga, and 124I); two unique PR phantoms were scanned and evaluated following OSEM reconstruction with and without PRC using different metrics, such as contrast recovery, contrast-to-noise ratio, image noise and the resolution evaluated in terms of full width at half maximum (FWHM). Results: The effect of PRC on 18F-imaging was negligible. In contrast, PRC improved image contrast for the 10-mm sphere of the NEMA image quality phantom filled with 68Ga and 124I by 33 and 24%, respectively. While the effect of PRC was less noticeable for the larger spheres, contrast recovery still improved by 5%. The spatial resolution was improved by 26% for 124I (FWHM of 4.9 vs. 3.7 mm). Conclusion: For high energy positron-emitting radionuclides, the proposed PRC method helped recover image contrast with reduced noise levels and with improved spatial resolution. As such, the PRC approach proposed here can help improve the quality of PET data in clinical practice and research.

Technical note: A PET/MR coil with an integrated, orbiting 511 keV transmission source for PET/MR imaging validated in an animal study.

BACKGROUND: MR-based methods for attenuation correction (AC) in PET/MRI either neglect attenuation of bone, or use MR-signal derived information about bone, which leads to a bias in quantification of tracer uptake in PET. In a previous study, we presented a PET/MRI specific MR coil with an integrated transmission source (TX) system allowing for direct measurement of attenuation. In phantom measurements, this system successfully reproduced the linear attenuation coefficient of water. PURPOSE: The purpose of this study is to validate the TX system in a clinical setting using animals and to show its applicability compared to standard clinical methods. METHODS: As test subject, a 15-kg piglet was injected with 53 MBq of 18F-NaF. The µ-map obtained with the TX system and the reconstructed activity distribution were compared to four established AC methods: a Dixon sequence, an ultra-short echo time (UTE) sequence, a CT scan, and a 511 keV transmission scan using a Siemens ECAT EXACT HR+ as the reference. The PET/MRI measurements were performed on a Siemens Biograph mMR to obtain the µ-map using the TX system as well as the Dixon and UTE sequence directly followed by the CT and ECAT measurements. RESULTS: The reconstructed activity distribution using the TX system for AC showed similar results compared to the reference (<5% difference in hot regions) and outperformed the MR-based methods as implemented in the PET/MRI system (<10% difference in hot regions). However, the additional hardware of the TX system adds complexity to the acquisition process. CONCLUSION: Our porcine study demonstrates the feasibility of post-injection transmission scans using the developed TX system in a clinical setting. This makes it a useful tool for PET/MRI in cases where transmission information is needed for AC. Potential applications are studies using larger animals where state-of-the-art atlas-based or artificial intelligence AC methods are not available.