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.

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.

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.

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.

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.

[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.

CT-based attenuation correction of whole-body radiotherapy treatment positioning devices in PET/MRI hybrid imaging.

OBJECTIVE: To implement computed tomography (CT)-based attenuation maps of radiotherapy (RT) positioning hardware and radiofrequency (RF) coils to enable hybrid positron emission tomography/magnetic resonance imaging (PET/MRI)-based RT treatment planning. MATERIALS AND METHODS: The RT positioning hardware consisted of a flat RT table overlay, coil holders for abdominal scans, coil holders for head and neck scans and an MRI compatible hip and leg immobilization device. CT images of each hardware element were acquired on a CT scanner. Based on the CT images, attenuation maps of the devices were created. Validation measurements were performed on a PET/MR scanner using a 68Ge phantom (48 MBq, 10 min scan time). Scans with each device in treatment position were performed. Then, reference scans containing only the phantom were taken. The scans were reconstructed online (at the PET/MRI scanner) and offline (via e7tools on a PC) using identical reconstruction parameters. Average reconstructed activity concentrations of the device and reference scans were compared. RESULTS: The device attenuation maps were successfully implemented. The RT positioning devices caused an average decrease of reconstructed PET activity concentration in the range between -8.3 ± 2.1% (mean ± SD) (head and neck coil holder with coils) to -1.0 ± 0.5% (abdominal coil holder). With attenuation correction taking into account RT hardware, these values were reduced to -2.0 ± 1.2% and -0.6 ± 0.5%, respectively. The results of the offline and online reconstructions were nearly identical, with a difference of up to 0.2%. CONCLUSION: The decrease in reconstructed activity concentration caused by the RT positioning devices is clinically relevant and can successfully be corrected using CT-based attenuation maps. Both the offline and online reconstruction methods are viable options.

Dose dependent cerebellar atrophy in glioma patients after radio(chemo)therapy.

BACKGROUND AND PURPOSE: Radiotherapy is a standard treatment option for high-grade gliomas. Brain atrophy has previously been associated with radiotherapy. The goal of this study was to investigate dose dependent cerebellar atrophy using prospective, longitudinal MR data from adult glioma patients who received radiotherapy. MATERIALS AND METHODS: Cerebellar volumes were measured using T1-weighted MR images from 91 glioma patients before radiotherapy (N = 91) and from longitudinal follow-ups acquired in three monthly intervals (N = 349). Relative cerebellar volumes were calculated as ratios to the corresponding baseline values. Univariate mixed effects models were used to determine factors that were significantly associated with relative cerebellar volumes. These factors were subsequently included as fixed effects in a final multivariate linear mixed effects model. RESULTS: In multivariate analysis, cerebellar volume decreased significantly as a function of time (p < 0.001), time × dose (p < 0.001) and patient age (p = 0.007). Considering a 55 year patient receiving a mean cerebellar dose of 0 Gy (10 Gy), the linear mixed effects model predicts a relative cerebellar volume loss of 0.4% (2.0%) after 1 year and 0.7% (3.6%) after 2 years. Compared to patients treated with photons, the cerebellar dose was significantly lower in patients treated with proton therapy (p < 0.001, r = 0.62). CONCLUSION: Cerebellar volume decreased significantly and irreversibly after radiotherapy as function of time and mean cerebellar dose. Further work is now needed to correlate these results with cognitive function and motor performance.

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.

Preliminary clinical assessment of dynamic carbon-11 methionine positron-emission tomography/computed tomography for the diagnosis of the pathologies in patients with musculoskeletal lesions: a prospective study.

BACKGROUND: This study prospectively assessed the diagnostic capacity of dynamic carbon-11 methionine (C-11 MET) positron-emission tomography (PET)/computed tomography for the diagnosis of pathologies in patients with primary unknown musculoskeletal lesions (MSLs). In total, 13 patients with MSLs underwent dynamic scans (5-10 [phase 1], 10-15 [phase 2], 15-20 [phase 3], 20-25 [phase 4], 25-30 [phase 5], and 30-35 [phase 6] min post-injection of C-11 MET). We statistically compared the maximum standardised uptake values (SUVmax) and corresponding retention index for dynamic scans (RI-SUV) for five benign MSLs (BMSLs), five primary malignant musculoskeletal tumours (PMMSTs), four metastatic musculoskeletal tumours (MMSTs), and three malignant lymphoma (ML) cases and explored their diagnostic capacities using receiver operating characteristic (ROC) curve analyses. RESULTS: SUVmax gradually decreased or remained similar with minimal fluctuations in all BMSL cases and four of five PMMST cases. In contrast, SUVmax increased over time in one case of PMMST and in all cases of MMST and ML. Significant differences were observed in SUVmax for all time phases and RI-SUV between BMSLs and MMSLs, in SUVmax for all time phases between PMMSTs and BMSLs, in SUVmax for all time phases and RI-SUV between non-PMMST-malignant tumours and BMSL, and in RI-SUV between non-PMMST-malignant tumours and PMMST. In ROC analyses, the areas under the curve yielded the highest values at 1.00 for differentiating most intergroup comparisons. CONCLUSIONS: Dynamic C-11 MET PET scans have the potential to be good predictors of discriminating MSLs in patients with primary unknown MSLs in clinical practice.

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.

Presynaptic dopamine function measured with [18F]fluorodopa and L-DOPA effects on impulsive choice.

We previously reported that L-DOPA effects on reward-based decision-making in a randomized, placebo-controlled, double-blind, crossover study were consistent with an inverted U-shaped function whereby both low and high extremes of dopamine signaling are associated with high-impulsive choice. To test this hypothesis, we performed [18F]DOPA positron emission tomography in 60 of the 87 participants in that study, and measured the effective distribution volume ratio (EDVR) of [18F]DOPA influx rate to [18F]dopamine washout rate, an index of presynaptic dopaminergic function. Participants with higher baseline EDVR self-reported lower impulsivity, and discounted rewards as a function of delay more strongly after receiving L-DOPA, whereas the opposite was detected for those with lower baseline EDVR. Our findings support a relationship of striatal dopaminergic activity to trait impulsivity, and the view that there is a non-linear, possibly inverted U-shaped relationship of striatal dopaminergic function with delay discounting. Individuals with optimal dopamine signaling would become more impulsive when receiving dopamine-enhancing drugs, whereas those with suboptimal dopaminergic signaling would benefit and exhibit less impulsive choice. Consideration of differences in endogenous dopamine signaling and possibly also other neurotransmitter activity may be crucial to advance understanding of the neurobiochemical mechanisms of impulsive decision-making and related mental disorders.

Putaminal Dopamine Turnover in de novo Parkinson's Disease Predicts Later Neuropsychiatric Fluctuations but Not Other Major Health Outcomes.

BACKGROUND AND OBJECTIVE: To investigate the predictive value of striatal dopamine turnover in patients with de novo Parkinson's disease (PD) for later occurrence of major non-motor health outcomes. METHODS: This retrospective, observer-blinded cohort study followed up 29 patients with de novo PD for a median of 10.7 years, who completed 18Fluorodopa PET imaging to measure striatal effective distribution volume ratio (EDVR, inverse of dopamine turnover) prior to antiparkinsonian treatment. Outcomes were assessed with a battery of non-motor, health-related quality-of-life and non-motor fluctuation (WOQ-19) measures and survival. RESULTS: During follow-up, 52% of patients developed wearing-off, 43% neuropsychiatric fluctuations, 35% sensory fluctuations, 32% dementia, 46% depression, 30% psychosis, and PD-related mortality was 26%. Patients with wearing-off and neuropsychiatric fluctuations showed significantly lower baseline EDVR (higher dopamine turnover) in the putamen but not in the caudate nucleus than those without these fluctuations. Consistently, baseline EDVR in the putamen predicted development of wearing-off and neuropsychiatric fluctuations with a lower risk with higher EDVR (lower dopamine turnover), whereas EDVR in caudate nucleus did not correlate with these fluctuations. No relationships were observed between baseline PET measures and the presence of other major health outcomes including survival. CONCLUSIONS: Lower putaminal dopamine turnover in de novo PD is associated with reduced risk for later neuropsychiatric fluctuations comprising a disease-intrinsic predisposing factor for their development, similar as reported for levodopa-induced motor complications. Striatal (putaminal/caudate) dopamine turnover is not predictive for other long-term major health outcomes. These results should be treated as hypothesis generating and require confirmation.

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.

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.

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.