Severe Dysbiosis and Specific Haemophilus and Neisseria Signatures as Hallmarks of the Oropharyngeal Microbiome in Critically Ill Coronavirus Disease 2019 (COVID-19) Patients.

BACKGROUND: At the entry site of respiratory virus infections, the oropharyngeal microbiome has been proposed as a major hub integrating viral and host immune signals. Early studies suggested that infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are associated with changes of the upper and lower airway microbiome, and that specific microbial signatures may predict coronavirus disease 2019 (COVID-19) illness. However, the results are not conclusive, as critical illness can drastically alter a patient's microbiome through multiple confounders. METHODS: To study oropharyngeal microbiome profiles in SARS-CoV-2 infection, clinical confounders, and prediction models in COVID-19, we performed a multicenter, cross-sectional clinical study analyzing oropharyngeal microbial metagenomes in healthy adults, patients with non-SARS-CoV-2 infections, or with mild, moderate, and severe COVID-19 (n = 322 participants). RESULTS: In contrast to mild infections, patients admitted to a hospital with moderate or severe COVID-19 showed dysbiotic microbial configurations, which were significantly pronounced in patients treated with broad-spectrum antibiotics, receiving invasive mechanical ventilation, or when sampling was performed during prolonged hospitalization. In contrast, specimens collected early after admission allowed us to segregate microbiome features predictive of hospital COVID-19 mortality utilizing machine learning models. Taxonomic signatures were found to perform better than models utilizing clinical variables with Neisseria and Haemophilus species abundances as most important features. CONCLUSIONS: In addition to the infection per se, several factors shape the oropharyngeal microbiome of severely affected COVID-19 patients and deserve consideration in the interpretation of the role of the microbiome in severe COVID-19. Nevertheless, we were able to extract microbial features that can help to predict clinical outcomes.

[Modern radiation therapy planning and image-guided radiotherapy using the example of prostate cancer]. / Moderne Bestrahlungsplanung und bildgeführte Strahlentherapie am Beispiel des Prostatakarzinoms.

CLINICAL/METHODICAL ISSUE: Optimizing radiotherapy demands precise delineation of the target structure, not only before but also during the course of radiotherapy. STANDARD RADIOLOGICAL METHODS: For many years, planning of external radiation treatment planning has been based on computer tomography data. METHODOLOGICAL INNOVATIONS: With the advent of image-guided radiotherapy (IGRT), magnetic resonance imaging (MRI) and functional hybrid imaging are increasingly being integrated into radiation treatment planning. The development of the MR-linac can be seen as an innovation. PERFORMANCE: The integration of MRI and hybrid imaging (positron emission tomography [PET]/CT, PET/MRI) in the treatment planning process enables more precise treatment planning due to the better morphological and functional information. The integration of MRI data on the MR-linac in daily position control enables adaptation of the irradiation plan to the current conditions. ACHIEVEMENTS: Technical innovation such as the MR-linac as well as increasing use of hybrid imaging contribute to the objective of further individualization within (radio)oncology. PRACTICAL RECOMMENDATIONS: Using the example of prostate cancer, the application of prostate-specific membrane antigen (PSMA) ligands and hybrid imaging offers great potential for individualized strategic treatment decisions. The MR-linac appears to be particularly suitable for radiation therapy of prostate cancer. Special attention must be paid to the technical aspects of positioning and data acquisition for the purpose of radiation treatment planning.

Germline SDHB-inactivating mutation in gastric spindle cell sarcoma.

Gastrointestinal stromal tumors (GISTs) are the most frequent mesenchymal tumors of the gastrointestinal tract. Inactivating mutations or epigenetic deregulation of succinate dehydrogenase complex (SDH) genes are considered defining features of a subset of GIST occurring in the stomach. Based on comprehensive molecular profiling and biochemical analysis within a precision oncology program, we identified hallmarks of SDH deficiency (germline SDHB-inactivating mutation accompanied by somatic loss of heterozygosity, lack of SDHB expression, global DNA hypermethylation, and elevated succinate/fumarate ratio) in a 40-year-old woman with undifferentiated gastric spindle cell sarcoma that did not meet the diagnostic criteria for other mesenchymal tumors of the stomach, including GIST. These data reveal that the loss of SDH function can be involved in the pathogenesis of non-GIST sarcoma of the gastrointestinal tract.

Olfactory dysfunction correlates with putaminal dopamine turnover in early de novo Parkinson's disease.

Although olfactory dysfunction is one of the most well-established prodromal symptoms in Parkinson's disease (PD), its correlation with clinical disease progression or dopaminergic dysfunction still remains unclear. We here evaluated the association of striatal dopamine metabolism and olfactory function in a homogenous cohort of 30 patients with early untreated de novo PD. Striatal dopamine metabolism was assessed by the extended 18Fluorodopa PET scanning protocol to measure 18Fluorodopa uptake (Kocc) and the effective dopamine distribution volume ratio (EDVR) as the inverse of dopamine turnover. Olfactory function was estimated by the "Sniffin' Sticks" test including odor threshold (T), discrimination (D) and identification (I) assessment. We detected moderate correlations of the EDVR in the posterior putamen with the TDI composite score (r = 0.412; p = 0.024; Pearson's correlation test) and the odor identification score (r = 0.444; p = 0.014). These correlations were confirmed by multivariate regression analyses using age, sex, symptom duration and disease severity as measured by UPDRSIII motor score as candidate covariates. No other associations were observed between olfaction measures and Kocc and EDVR in all striatal regions. Together, olfactory dysfunction in early PD is not correlated with striatal 18Fluorodopa uptake as a measure for dopaminergic degeneration, but with putaminal dopamine turnover as a marker for dopaminergic presynaptic compensatory processes in early PD. These results should be treated as hypothesis generating and require confirmation by larger multicenter studies.

FDG-PET/MRI in patients with pelvic recurrence of rectal cancer: first clinical experiences.

OBJECTIVES: To determine the value of 18F-FDG-PET/MRI in the diagnosis and management of patients with pelvic recurrence of rectal cancer. METHODS: Forty-four patients (16 women, 28 men) with a history of rectal cancer who received FDG-PET/MRI between June 2011 and February 2017 at our institution were retrospectively enrolled. Three patients received two FDG-PET/MRIs; thus a total of 47 examinations were included. Pelvic recurrence was confirmed either with histology (n = 27) or imaging follow-up (n = 17) (> 4 months). Two readers (one radiologist, one nuclear medicine physician) interpreted the images in consensus. Pelvic lesions were assessed regarding FDG uptake and morphology. Sensitivity, specificity, positive and negative predictive values as well as accuracy of PET/MRI in detecting recurrence were determined. RESULTS: In 47 FDG-PET/MRIs 30 suspicious pelvic lesions were identified, 29 of which were malignant. Two patients underwent resection and had histologically proven pelvic recurrence without showing suspicious findings on FDG-PET/MRI. Changes in management due to FDG-PET/MRI findings had been implemented in eight patients. Eighty per cent (16/20) of resected patients had histologically negative resection margins (R0), one patient had uncertain resection margins. Sensitivity of FDG-PET/MRI in detecting recurrence was 94%, specificity 94%, positive/negative predictive value and accuracy were 97%, 90% and 94%, respectively. CONCLUSIONS: FDG-PET/MRI is a valuable tool in the diagnosis and staging of pelvic recurrence in patients with rectal cancer. KEY POINTS: • Metabolic information obtained from PET coupled with excellent soft tissue contrast from MRI could facilitate detection of rectal cancer recurrence and assist in treatment planning. • PET/MRI demonstrates high sensitivity and specificity for the diagnosis of local recurrence of rectal cancer • PET/MRI led to alterations in management in 18.2% of patients.

Correction to: FDG-PET/MRI in patients with pelvic recurrence of rectal cancer: first clinical experiences.

The original version of this article, published on 6 July 2018, unfortunately contained a mistake.

Functional monoamine oxidase B gene intron 13 polymorphism predicts putaminal dopamine turnover in de novo Parkinson's disease.

OBJECTIVE: The objective of this study was to evaluate the effects of common functional polymorphisms in genes involved in dopamine metabolism on striatal dopamine turnover in de novo Parkinson's disease (PD). METHODS: This was an observer-blinded cohort study investigating effects of common functional polymorphisms in dopa decarboxylase (DDC, rs921451), monoamine oxidase B (MAOB; rs1799836), catechol-O-methyltransferase (COMT, rs4680), and dopamine transporter/solute carrier family 6 member 3 (DAT/SLC6A3, variable number tandem repeats) genes on 18 F-fluorodopa uptake and an effective distribution volume ratio (inverse of dopamine turnover) measured by 18 F-fluorodopa PET in 28 untreated PD patients. RESULTS: Patients carrying the MAOBCC/(C)/CT genotype (low/intermediate enzyme activity) had a lower dopamine turnover in the putamen (higher mean effective distribution volume ratio) when compared with patients with MAOBTT/(T) genotype (high enzyme activity). Striatal PET measures were not different between variants in the remaining genes. CONCLUSIONS: The MAOB (rs1799836) polymorphism predicts putaminal dopamine turnover in early PD with the MAOBTT allele linked to high enzyme activity leading to higher intrinsic dopamine turnover, which has been demonstrated to constitute a risk factor for motor complications. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

PET imaging in adaptive radiotherapy of prostate tumors.

The integration of data from positron-emission-tomography, combined with computed tomography as positron emission tomography computed tomography (PET/CT) or combined with magnet resonance imaging as PET/MRI, into radiation treatment planning of prostate cancer is gaining higher impact with the development of more sensitive and specific radioligands. The classic PET-tracer for prostate cancer imaging are [11C]choline and [11C]acetate, which are currently outperformed by ligands binding to the prostate-specific-membrane-antigen (PSMA). [68Ga]PSMA-11, which is the most frequently applied tracer, has shown to detect lymph node metastases, local recurrences, distant metastases and intraprostatic foci with high sensitivity, even at relatively low PSA levels. The results from PET-imaging may influence radiotherapeutic management at different stages of the disease i.e. during primary staging or biochemical recurrence, when the detection of distant metastases may alter the curative treatment concept into a palliative approach. On the other hand, the clinical target volume could be adapted by visualizing lymph node metastases at locations, which might not have been suspicious on morphologic imaging alone. The treatment plan might contain a boost to the dominant intraprostatic lesion, which could be delineated by a combination of PET-tracer uptake and multiparametric MRI. Therefore, PSMA-PET imaging is well suited for being integrated into prostate radiation planning. However, further prospective trials evaluating the impact on oncological outcome are indicated.

[PET/MRI]. / PET/MRT.

CLINICAL/METHODICAL ISSUE: Magnet resonance imaging (MRI) is an excellent anatomical reference method for the combination with positron emission tomography (PET). But MRI does not produce data, which can be directly used for attenuation correction of PET data, potentially compromising quantitative accuracy of PET. STANDARD RADIOLOGICAL METHODS: Hybrid-positron emission tomography/computed tomography (PET/CT) is an established standard diagnostic tool, particularly for staging and restaging in oncology. Attenuation correction of PET data is performed with a µMAP derived from low-dose-CT, considered as a robust method. METHODICAL INNOVATIONS: Using standardized MRI-sequences, tissue classes are segmented and attenuation maps are obtained, based on empirical density values. In addition, new reconstruction algorithms and the possibility to acquire PET and MRI simultaneously with MRI-based motion correction are available. These advances have improved image quality and quantitative accuracy of the PET-data in PET/MRI. PERFORMANCE: In numerous oncological studies PET/CT and PET/MR were rated as equal in their diagnostic performance. The combination of functional-metabolic PET and multiparametric MRI with excellent soft tissue contrast complement each other with regard to their diagnostic information in numerous tumor entities. PRACTICAL RECOMMENDATIONS: The standard diagnostic workup for lung cancer is currently still based on PET/CT. In numerous tumor entities, the combination of PET/MRI can provide additional diagnostic information.

Radiomics for residual tumour detection and prognosis in newly diagnosed glioblastoma based on postoperative [11C] methionine PET and T1c-w MRI.

Personalized treatment strategies based on non-invasive biomarkers have potential to improve patient management in patients with newly diagnosed glioblastoma (GBM). The residual tumour burden after surgery in GBM patients is a prognostic imaging biomarker. However, in clinical patient management, its assessment is a manual and time-consuming process that is at risk of inter-rater variability. Furthermore, the prediction of patient outcome prior to radiotherapy may identify patient subgroups that could benefit from escalated radiotherapy doses. Therefore, in this study, we investigate the capabilities of traditional radiomics and 3D convolutional neural networks for automatic detection of the residual tumour status and to prognosticate time-to-recurrence (TTR) and overall survival (OS) in GBM using postoperative [11C] methionine positron emission tomography (MET-PET) and gadolinium-enhanced T1-w magnetic resonance imaging (MRI). On the independent test data, the 3D-DenseNet model based on MET-PET achieved the best performance for residual tumour detection, while the logistic regression model with conventional radiomics features performed best for T1c-w MRI (AUC: MET-PET 0.95, T1c-w MRI 0.78). For the prognosis of TTR and OS, the 3D-DenseNet model based on MET-PET integrated with age and MGMT status achieved the best performance (Concordance-Index: TTR 0.68, OS 0.65). In conclusion, we showed that both deep-learning and conventional radiomics have potential value for supporting image-based assessment and prognosis in GBM. After prospective validation, these models may be considered for treatment personalization.

PET/MRI in head and neck cancer: initial experience.

PURPOSE: To evaluate the feasibility of PET/MRI (positron emission tomography/magnetic resonance imaging) with FDG ((18)F-fluorodeoxyglucose) for initial staging of head and neck cancer. METHODS: The study group comprised 20 patients (16 men, 4 women) aged between 52 and 81 years (median 64 years) with histologically proven squamous cell carcinoma of the head and neck region. The patients underwent a PET scan on a conventional scanner and a subsequent PET/MRI examination on a whole-body hybrid system. FDG was administered intravenously prior to the conventional PET scan (267-395 MBq FDG, 348 MBq on average). The maximum standardized uptake values (SUV(max)) of the tumour and of both cerebellar hemispheres were determined for both PET datasets. The numbers of lymph nodes with increased FDG uptake were compared between the two PET datasets. RESULTS: No MRI-induced artefacts where observed in the PET images. The tumour was detected by PET/MRI in 17 of the 20 patients, by PET in 16 and by MRI in 14. The PET/MRI examination yielded significantly higher SUV(max) than the conventional PET scanner for both the tumour (p < 0.0001) and the cerebellum (p = 0.0009). The number of lymph nodes with increased FDG uptake detected using the PET dataset from the PET/MRI system was significantly higher the number detected by the stand-alone PET system (64 vs. 39, p = 0.001). CONCLUSION: The current study demonstrated that PET/MRI of the whole head and neck region is feasible with a whole-body PET/MRI system without impairment of PET or MR image quality.

PET/MR for therapy response evaluation in malignant lymphoma: initial experience.

OBJECT: To evaluate the feasibility of positron emission tomography/magnetic resonance imaging (PET/MR) with (18)fluoro-2-deoxyglucose (FDG) for therapy response evaluation of malignant lymphoma. MATERIALS AND METHODS: Nine patients with malignant lymphoma who underwent FDG-PET/MR before and after chemotherapy were included in this retrospective study. Average time between the two scans was 70 days. The scans were evaluated independently by two nuclear medicine physicians. The Ann Arbor classification was used to describe lymphoma stage. Furthermore, the readers also rated PET image quality using a five point scale. Weighted kappa (κ) was used to calculate interrater agreement. RESULTS: The initial scan showed foci of increased FDG uptake in all patients, with Ann Arbor stage varying between I and IV. In the follow-up examination, all but one patient showed complete response to chemotherapy. PET image quality was rated as very good or excellent for all scans. Interrater agreement was excellent regarding Ann Arbor stage (κ = 0.97) and good regarding image quality (κ = 0.41). CONCLUSION: PET/MR shows promising initial results for therapy response evaluation in lymphoma patients.

Quantitative accuracy of attenuation correction in the Philips Ingenuity TF whole-body PET/MR system: a direct comparison with transmission-based attenuation correction.

OBJECTIVE: Evaluation of the quantitative accuracy of MR-based attenuation correction (MRAC) in the Philips Ingenuity TF whole-body PET/MR. MATERIALS AND METHODS: In 13 patients, PET emission data from the PET/MR were reconstructed using two different methods for attenuation correction. In the first reconstruction, the vendor-provided standard MRAC was used. In the second reconstruction, a coregistered transmission-based attenuation map from a second immediately preceding investigation with a stand-alone Siemens ECAT EXACT HR(+) PET scanner was used (TRAC). The two attenuation maps were compared regarding occurrence of segmentation artifacts in the MRAC procedure. Standard uptake values (SUVs) of multiple VOIs (liver, cerebellum, hot focal structures at various locations in the trunk) were compared between both reconstructed data sets. Furthermore, a voxel-wise intensity correlation analysis of both data sets in the lung and trunk was performed. RESULTS: VOI averaged SUV differences between MRAC and TRAC were as follows (relative differences, mean ± standard deviation): (+12 ± 6) % cerebellum, (-4 ± 9) % liver, (-2 ± 11) % hot focal structures. The fitted slopes of the voxel-wise correlations in the lung and trunk were 0.87 ± 0.17 and 0.95 ± 0.10 with averaged adjusted R (2) values of 0.96 and 0.98, respectively. These figures include two instances with partially erroneous lung segmentation due to artifacts in the underlying MR images. CONCLUSION: The MR-based attenuation correction implemented on the Philips Ingenuity PET/MR provides reasonable quantitative accuracy. On average, deviations from TRAC-based results are small (on the order of 10% or below) across the trunk, but due to interindividual variability of the segmentation quality, deviations of more than 20% can occur. Future improvement of the segmentation quality would help to increase the quantitation accuracy further and to reduce the inter-subject variability.

Comparison of dopamine turnover, dopamine influx constant and activity ratio of striatum and occipital brain with ¹8F-dopa brain PET in normal controls and patients with Parkinson's disease.

PURPOSE: The aim of the study was to estimate normal ranges and test-retest measures for various parameters characterising dopamine metabolism from a prolonged (18)F-dopa positron emission tomography (PET) measurement using a reference tissue model and compare their value for the detection of early Parkinson's disease (PD). METHODS: Healthy volunteers (n = 9) and patients (n = 36) in an early stage of PD underwent an (18)F-dopa PET measurement lasting 4 h. The influx rate constant k(occ) and the effective distribution volume ratio (EDVR, its inverse is an indicator for dopamine turnover) were estimated by a graphical approach using dynamic data in the striatum and, as a reference region, the occipital cortex. Furthermore, ratios of activity concentrations between striatum and occipital brain taken for three time intervals completed the data analysis. All parameters were determined both in eight small volumes of interest placed in the striatum as well as averaged for caudate nucleus and putamen. For the control group, reproducibility was checked in a second study 3 months later and ranges for normal values were derived from mean ± 2 standard deviations. Receiver-operating characteristic (ROC) analyses were performed to assess the value of the parameters for diagnostic purposes. RESULTS: Patients with early-stage PD and healthy volunteers could be separated by the values of the putamen, not the caudate nucleus. The normal ranges of the putamen were 0.0151-0.0216/min for the influx rate constant k(occ) and 2.02-3.00 for EDVR. For the various time intervals used the striato-occipital ratios yielded 2.24-3.06, 2.43-3.42 and 2.35-3.21, respectively. Patients were characterised by significantly lower values (p < 0.001) and significant differences between ipsi- and contralateral sides (p < 0.001) with regard to their clinical symptoms and a rostrocaudal gradient. EDVR as well as k(occ) for the putamen were able to effectively differentiate between groups (sensitivity >97%, specificity 100%). In contrast, striato-occipital ratios showed a sensitivity of about only 85%. CONCLUSION: For clinical applications, our data do not demonstrate any superiority of the EDVR determination compared to influx rate constant, while requiring long and tedious acquisition protocols. The normal range estimates do not represent absolute quantitative measures for dopamine metabolism but are specific for the chosen acquisition and processing procedures.

Adapting Imaging Protocols for PET-CT and PET-MRI for Immunotherapy Monitoring.

Hybrid imaging with positron emission tomography (PET) in combination with computer tomography (CT) is a well-established diagnostic tool in oncological staging and restaging. The combination of PET with magnetic resonance imaging (MRI) as a clinical scanner was introduced approximately 10 years ago. Although MRI provides superb soft tissue contrast and functional information without the radiation exposure of CT, PET-MRI is not as widely introduced in oncologic imaging as PET-CT. One reason for this hesitancy lies in the relatively long acquisition times for a PET-MRI scan, if the full diagnostic potential of MRI is exploited. In this review, we discuss the possible advantages of combined imaging protocols of PET-CT and PET-MRI, within the context of staging and restaging of patients under immunotherapy, in order to achieve "multi-hybrid imaging" in one single patient visit.

Technical Note: On the feasibility of performing dosimetry in target and organ at risk using polymer dosimetry gel and thermoluminescence detectors in an anthropomorphic, deformable, and multimodal pelvis phantom.

OBJECTIVE: To assess the feasibility of performing dose measurements in the target (prostate) and an adjacent organ at risk (rectum) using polymer dosimetry gel and thermoluminescence detectors (TLDs) in an anthropomorphic, deformable, and multimodal pelvis phantom (ADAM PETer). METHODS: The 3D printed prostate organ surrogate of the ADAM PETer phantom was filled with polymer dosimetry gel. Nine TLD600 (LiF:Mg,Ti) were installed in 3 × 3 rows on a specifically designed 3D-printed TLD holder. The TLD holder was inserted into the rectum at the level of the prostate and fixed by a partially inflated endorectal balloon. Computed tomography (CT) images were taken and treatment planning was performed. A prescribed dose of 4.5 Gy was delivered to the planning target volume (PTV). The doses measured by the dosimetry gel in the prostate and the TLDs in the rectum ("measured dose") were compared to the doses calculated by the treatment planning system ("planned dose") on a voxel-by-voxel basis. RESULTS: In the prostate organ surrogate, the 3D-γ-index was 97.7% for the 3% dose difference and 3 mm distance to agreement criterium. In the center of the prostate organ surrogate, measured and planned doses showed only minor deviations (<0.1 Gy, corresponding to a percentage error of 2.22%). On the edges of the prostate, slight differences between planned and measured doses were detected with a maximum deviation of 0.24 Gy, corresponding to 5.3% of the prescribed dose. The difference between planned and measured doses in the TLDs was on average 0.08 Gy (range: 0.02-0.21 Gy), corresponding to 1.78% of the prescribed dose (range: 0.44%-4.67%). CONCLUSIONS: The present study demonstrates the feasibility of using polymer dosimetry gel and TLDs for 3D and 1D dose measurements in the prostate and the rectum organ surrogates in an anthropomorphic, deformable and multimodal phantom. The described methodology might offer new perspectives for end-to-end tests in image-guided adaptive radiotherapy workflows.

Clinical application of dynamic 18F-fluorodeoxyglucose positron-emission tomography / computed tomography in the differential diagnoses of musculoskeletal lesions.

We aimed to assess the differential diagnostic efficacy of dynamic F-18 fluorodeoxyglucose (FDG) positron emission tomography / computed tomography (PET / CT) and to evaluate the appropriate scan timings for diagnosis of musculoskeletal lesions (MSLs). Dynamic scans (5-15 [phase 1], 15-25 [phase 2], and 25-35 [phase 3] min after F-18 FDG injection) and dual-time-point scans (1 and 2 h after injection) were acquired for 23 MSLs [4 benign MSLs (BMSLs). 10 primary malignant musculoskeletal tumors (PMMSTs), and 9 metastatic musculoskeletal tumors (MMSTs)]. We compared the maximum standardized uptake values (SUVmax) and corresponding retention indices for dynamic (RI-SUVdyn) and dual-time-point (RI-SUVdual) scans and evaluated diagnostic efficacy using receiver operating characteristic (ROC) curve analyses. The SUVmax gradually decreased or was almost identical with minimal fluctuation in 3 BMSLs and 1 PMMST. SUVmax increased over time after phase 2 in 18 malignant MSLs (MMSLs). There were significant differences in SUVmax (for all time phases) and RI-SUV dual between BMSLs and MMSLs and between PMMSTs and MMSTs. In the ROC analyses, the areas under the curve for SUV in phases 2 and 3 were highest for differentiating BMSLs from MMSLs and PMMSTs from MMSTs, respectively. Dynamic F-18 FDG PET / CT is valuable for diagnosis of musculoskeletal lesions. J. Med. Invest. 68 : 96-104, February, 2021.

Technical Note: ADAM PETer - An anthropomorphic, deformable and multimodality pelvis phantom with positron emission tomography extension for radiotherapy.

OBJECTIVE: To develop an anthropomorphic, deformable and multimodal pelvis phantom with positron emission tomography extension for radiotherapy (ADAM PETer). METHODS: The design of ADAM PETer was based on our previous pelvis phantom (ADAM) and extended for compatibility with PET and use in 3T magnetic resonance imaging (MRI). The formerly manually manufactured silicon organ surrogates were replaced by three-dimensional (3D) printed organ shells. Two intraprostatic lesions, four iliac lymph node metastases and two pelvic bone metastases were added to simulate prostate cancer as multifocal and metastatic disease. Radiological properties [computed tomography (CT) and 3T MRI] of cortical bone, bone marrow and adipose tissue were simulated by heavy gypsum, a mixture of Vaseline and K2 HPO4 and peanut oil, respectively. For soft tissues, agarose gels with varying concentrations of agarose, gadolinium (Gd) and sodium fluoride (NaF) were developed. The agarose gels were doped with patient-specific activity concentrations of a Fluorine-18 labelled compound and then filled into the 3D printed organ shells of prostate lesions, lymph node and bone metastases. The phantom was imaged at a dual energy CT and a 3T PET/MRI scanner. RESULTS: The compositions of the soft tissue surrogates are the following (given as mass fractions of agarose[w%]/NaF[w%]/Gd[w%]): Muscle (4/1/0.027), prostate (1.35/4.2/0.011), prostate lesions (2.25/4.2/0.0085), lymph node and bone metastases (1.4/4.2/0.025). In all imaging modalities, the phantom simulates human contrast. Intraprostatic lesions appear hypointense as compared to the surrounding normal prostate tissue in T2-weighted MRI. The PET signal of all tumors can be localized as focal spots at their respective site. Activity concentrations of 12.0 kBq/mL (prostate lesion), 12.4 kBq/mL (lymph nodes) and 39.5 kBq/mL (bone metastases) were measured. CONCLUSION: The ADAM PETer pelvis phantom can be used as multimodal, anthropomorphic model for CT, 3T-MRI and PET measurements. It will be central to simulate and optimize the technical workflow for the integration of PET/MRI-based radiation treatment planning of prostate cancer patients.

Final Results of the Prospective Biomarker Trial PETra: [11C]-MET-Accumulation in Postoperative PET/MRI Predicts Outcome after Radiochemotherapy in Glioblastoma.

PURPOSE: This prospective trial investigates the association of time to recurrence (TTR) in glioblastoma with [11C]methionine (MET) tracer uptake before postoperative radiochemotherapy (RCT) aiming to guide radiotherapy boost regions. EXPERIMENTAL DESIGN: Between 2013 and 2016, 102 patients with glioblastoma were recruited. RCT was performed with concurrent and adjuvant temozolomide to a total dose of 60 Gy. Tumor residues in postresection PET and MRI were together defined as gross tumor volumes for radiotherapy treatment planning. [11C]methionine (MET)-PET/MRI was performed before RCT and at each follow-up. RESULTS: The primary hypothesis of a longer TTR for patients without increased tracer accumulation in postoperative MET-PET was confirmed in 89 patients. With 18.9 months (95% confidence interval, 9.3-28.5 months), median TTR was significantly (P < 0.001) longer for patients without (n = 29, 32.6%) as compared with 6.3 months (3.6-8.9) for patients with MET accumulation (n = 60, 67.4%) in pre-RCT PET. Although MRI often did not detect all PET-positive regions, an unfavorable impact of residual tumor in postsurgical MRI (n = 38, 42.7%) on TTR was observed [4.6 (4.2-5.1) vs. 15.5 months (6.0-24.9), P < 0.001]. Significant multivariable predictors for TTR were MRI positivity, PET-positive volume, and O6-methylguanine DNA methyltransferase (MGMT) hypermethylation. CONCLUSIONS: Postsurgical amino acid PET has prognostic value for TTR after RCT in glioblastoma. Because of the added value of the metabolic beyond the pure structural information, it should complement MRI in radiotherapy planning if available with reasonable effort, at least in the context of maximal therapy. Furthermore, the spatial correlation of regions of recurrence with PET-positive volumes could provide a bioimaging basis for further trials, for example, testing local radiation dose escalation.