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Simple Summary PET using radiolabelled amino acids has become an essential tool for diagnosing brain tumours in addition to MRI. O-(2-[F-18]fluoroethyl)-L-tyrosine (FET) is one of the most successful tracers in the field. We analysed our database of 6534 FET PET examinations regarding the diagnostic needs and preferences of the referring physicians for FET PET in the clinical decision-making process. The demand for FET PET increased considerably in the last decade, especially for differentiating tumour progress from treatment-related changes in gliomas. Accordingly, referring physicians rated the diagnostics of recurrent glioma and recurrent brain metastases as the most relevant indication for FET PET. The analysis and survey results confirm the high relevance of FET PET in the clinical diagnosis of brain tumours and support the need for approval for routine use. O-(2-[F-18]fluoroethyl)-L-tyrosine (FET) is a widely used amino acid tracer for positron emission tomography (PET) imaging of brain tumours. This retrospective study and survey aimed to analyse our extensive database regarding the development of FET PET investigations, indications, and the referring physicians' rating concerning the role of FET PET in the clinical decision-making process. Between 2006 and 2019, we performed 6534 FET PET scans on 3928 different patients against a backdrop of growing demand for FET PET. In 2019, indications for the use of FET PET were as follows: suspected recurrent glioma (46%), unclear brain lesions (20%), treatment monitoring (19%), and suspected recurrent brain metastasis (13%). The referring physicians were neurosurgeons (60%), neurologists (19%), radiation oncologists (11%), general oncologists (3%), and other physicians (7%). Most patients travelled 50 to 75 km, but 9% travelled more than 200 km. The role of FET PET in decision-making in clinical practice was evaluated by a questionnaire consisting of 30 questions, which was filled out by 23 referring physicians with l

Accurate scatter correction is essential for qualitative and quantitative PET imaging. Until now, scatter correction based on Monte Carlo simulation (MCS) has been recognized as the most accurate method of scatter correction for PET. However, the major disadvantage of MCS is its long computational time, which makes it unfeasible for clinical usage. Meanwhile, single scatter simulation (SSS) is the most widely used method for scatter correction. Nevertheless, SSS has the disadvantage of limited robustness for dynamic measurements and for the measurement of large objects. In this work, a newly developed implementation of MCS using graphics processing unit (GPU) acceleration is employed, allowing full MCS-based scatter correction in clinical 3D brain PET imaging. Starting from the generation of annihilation photons to their detection in the simulated PET scanner, all relevant physical interactions and transport phenomena of the photons were simulated on GPUs. This resulted in an expected distribution of scattered events, which was subsequently used to correct the measured emission data. The accuracy of the approach was validated with simulations using GATE (Geant4 Application for Tomography Emission), and its performance was compared to SSS. The comparison of the computation time between a GPU and a single-threaded CPU showed an acceleration factor of 776 for a voxelized brain phantom study. The speedup of the MCS implemented on the GPU represents a major step toward the application of the more accurate MCS-based scatter correction for PET imaging in clinical routine.

Assessment of residual tumor after resection of cerebral gliomas can be difficult with MRI and may be improved by amino acid PET. The aim of this experimental study was to investigate uptake of 2-F-18-fluoroethyl-L-tyrosine (F-18-FET) and L-[methyl-H-3]-methionine (H-3-MET) in residual tumor after surgery and possible false-positive uptake in treatment-related changes. Methods: F98 or GS-9L rat gliomas were implanted into the brain of 64 rats. Tumors were resected after 1 wk of tumor growth, and sham surgery was performed in an additional 10 animals. At different time points after surgery (1, 2, 3, 7, and 14-16 d), rats underwent ex vivo dual-tracer autoradiography using F-18-FET and H-3-MET. Histologic slices were evaluated by immunostaining for cell density and astrogliosis. Tracer uptake was quantified by lesion-to-brain ratios (L/B) at the rim of the resection cavity (considered treatment-related uptake) and in residual or recurrent tumor tissue. Four animals showing no residual tumor underwent PET 3 d after surgery to examine time-activity curves of F-18-FET uptake in treatment-related changes. Results: Treatment-related uptake with a mean L/B of 2.0 +/- 0.3 for F-18-FET and a mean L/B of 1.7 +/- 0.2 for H-3-MET was noted at the rim of the resection cavity in the first week after surgery, decreasing significantly by 14-16 d (P < 0.01). Treatment-related tracer uptake was significantly higher for F-18-FET than for H-3-MET (P< 0.001). Tracer uptake in rat gliomas exceeded treatment-related tracer uptake at all time points (P < 0.001), but the latter was in the range of human gliomas. Reactive astrogliosis was noted near the resection cavity from the second day after surgery. Time-activity curves of F-18-FET uptake in those areas revealed constantly increasing uptake. Conclusion: Surgery may induce significant treatment-related F-18-FET and H-3-MET uptake near the resection cavity in the first week after surgery, presumably caused by reactive astrogliosis. Treatme

Despite the fact that MRI has evolved to become the standard method for diagnosis and monitoring of patients with brain tumours, conventional MRI sequences have two key limitations: the inability to show the full extent of the tumour and the inability to differentiate neoplastic tissue from nonspecific, treatment-related changes after surgery, radiotherapy, chemotherapy or immunotherapy. In the past decade, PET involving the use of radiolabelled amino acids has developed into an important diagnostic tool to overcome some of the shortcomings of conventional MRI. The Response Assessment in Neuro-Oncology working group - an international effort to develop new standardized response criteria for clinical trials in brain tumours - has recommended the additional use of amino acid PET imaging for brain tumour management. Concurrently, a number of advanced MRI techniques such as magnetic resonance spectroscopic imaging and perfusion weighted imaging are under clinical evaluation to target the same diagnostic problems. This Review summarizes the clinical role of amino acid PET in relation to advanced MRI techniques for differential diagnosis of brain tumours; delineation of tumour extent for treatment planning and biopsy guidance; post-treatment differentiation between tumour progression or recurrence versus treatment-related changes; and monitoring response to therapy. An outlook for future developments in PET and MRI techniques is also presented.

We aimed to evaluate the diagnostic potential of dual-time-point imaging with positron emission tomography (PET) using O-(2-[F-18]fluoroethyl)-L-tyrosine (F-18-FET) for non-invasive grading of cerebral gliomas compared with a dynamic approach. Thirty-six patients with histologically confirmed cerebral gliomas (21 primary, 15 recurrent; 24 high-grade, 12 low-grade) underwent dynamic PET from 0 to 50 min post-injection (p.i.) of F-18-FET, and additionally from 70 to 90 min p.i. Mean tumour-to-brain ratios (TBRmean) of F-18-FET uptake were determined in early (20-40 min p.i.) and late (70-90 min p.i.) examinations. Time-activity curves (TAC) of the tumours from 0 to 50 min after injection were assigned to different patterns. The diagnostic accuracy of changes of F-18-FET uptake between early and late examinations for tumour grading was compared to that of curve pattern analysis from 0 to 50 min p.i. of F-18-FET. The diagnostic accuracy of changes of the TBRmean of F-18-FET PET uptake between early and late examinations for the identification of HGG was 81 % (sensitivity 83 %; specificity 75 %; cutoff - 8 %; p < 0.001), and 83 % for curve pattern analysis (sensitivity 88 %; specificity 75 %; p < 0.001). Dual-time-point imaging of F-18-FET uptake in gliomas achieves diagnostic accuracy for tumour grading that is similar to the more time-consuming dynamic data acquisition protocol. Dual-time-point imaging is equivalent to dynamic FET PET for grading of gliomas. Dual-time-point imaging is less time consuming than dynamic FET PET. Costs can be reduced due to higher patient throughput. Reduced imaging time increases patient comfort and sedation might be avoided. Quicker image interpretation is possible, as no curve evaluation is necessary.

Diffusion of water molecules in the human brain tissue has strong similarities with diffusion in porous media. It is affected by different factors such as restrictions and compartmentalization, interaction with membrane walls, strong anisotropy imposed by cellular microstructure, etc. However, multiple artefacts abound in in vivo measurements either from subject motions, such as cardiac pulsation, bulk head motion, respiratory motion, and involuntary tics and tremor, or hardware related problems, such as table vibrations, etc. All these artefacts can substantially degrade the resulting images and render postprocessing diffusion analysis difficult or even impossible. In order to overcome these problems, we have developed a robust and efficient approach based on the least trimmed squares algorithm that works well with severely degraded datasets with low signal-to-noise ratio. This approach has been compared with other diffusion imaging post-processing algorithms using simulations and in vivo experiments. We demonstrate that the least trimmed squares algorithm can be easily adopted for multiple non-Gaussian diffusion models such as the biexponential model. The developed approach is shown to exhibit a high efficiency and accuracy and can, in principle, be exploited in other diffusion studies where artefact/outlier suppression is demanded.