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Radioembolization is an established treatment for chemoresistant and unresectable liver cancers. Currently, treatment planning is often based on semi-empirical methods, which yield acceptable toxicity profiles and have enabled the large-scale application in a palliative setting. However, recently, five large randomized controlled trials using resin microspheres failed to demonstrate a significant improvement in either progression-free survival or overall survival in both hepatocellular carcinoma and metastatic colorectal cancer. One reason for this might be that the activity prescription methods used in these studies are suboptimal for many patients.In this review, the current dosimetric methods and their caveats are evaluated. Furthermore, the current state-of-the-art of image-guided dosimetry and advanced radiobiological modeling is reviewed from a physics' perspective. The current literature is explored for the observation of robust dose-response relationships followed by an overview of recent advancements in quantitative image reconstruction in relation to image-guided dosimetry.This review is concluded with a discussion on areas where further research is necessary in order to arrive at a personalized treatment method that provides optimal tumor control and is clinically feasible.

BACKGROUND: Positron emission tomography (PET) has had a transformative impact on oncological and neurological applications. However, still much of PET's potential remains untapped with limitations primarily driven by low spatial resolution, which severely hampers accurate quantitative PET imaging via the partial volume effect (PVE). PURPOSE: We present experimental results of a practical and cost-effective ultra-high resolution brain-dedicated PET scanner, using our depth-encoding Prism-PET detectors arranged along a compact and conformal gantry, showing substantial reduction in PVE and accurate radiotracer uptake quantification in small regions. METHODS: lutetium yttrium oxyorthosillicate (LYSO) scintillator crystals coupled 4-to-1 to an 8 × 8 array of silicon photomultiplier (SiPM) pixels on one end and to a prismatoid light guide array on the opposite end. The scanner's performance was evaluated by measuring depth-of-interaction (DOI) resolution, energy resolution, timing resolution, spatial resolution, sensitivity, and image quality of ultra-micro Derenzo and three-dimensional (3D) Hoffman brain phantoms. RESULTS: The full width at half maximum (FWHM) DOI, energy, and timing resolutions of the scanner are 2.85 mm, 12.6%, and 271 ps, respectively. Not considering artifacts due to mechanical misalignment of detector blocks, the intrinsic spatial resolution is 0.89-mm FWHM. Point source images reconstructed with 3D filtered back-projection (FBP) show an average spatial resolution of 1.53-mm FWHM across the entire FOV. The peak absolute sensitivity is 1.2% for an energy window of 400-650 keV. The ultra-micro Derenzo phantom study demonstrates the highest reported spatial resolution performance for a human brain PET scanner with perfect reconstruction of 1.00-mm diameter hot-rods. Reconstructed images of customized Hoffman brain phantoms prove that Prism-PET enables accurate radiotracer uptake quantification in small brain regions (2-3 mm). CONCLUSIONS: Prism-PET will substantially strengthen the utility of quantitative PET in neurology for early diagnosis of neurodegenerative diseases, and in neuro-oncology for improved management of both primary and metastatic brain tumors.

PURPOSE: Ac]Ac-PSMA-I&T treatment. METHODS: Lu, respectively. RESULTS: Lu]Lu-PSMA-I&T lesion SUV were significantly higher (p = 0.03; 1.8 ± 1.1 vs. 2.1 ± 1.5). For absorbed dose estimates, significant differences regarding the kidneys remained, while no significant differences for lesion dosimetry were found. CONCLUSION: Bi in the kidneys.

F PET imaging. This review is expected to facilitate harmonization of quantitative PET and to promote the contribution of PET-derived biomarkers to research and development in medicine.

The purpose of these guidelines is to assist physicians in recommending, performing, interpreting and reporting the results of FDG PET/CT for oncological imaging of adult patients. PET is a quantitative imaging technique and therefore requires a common quality control (QC)/quality assurance (QA) procedure to maintain the accuracy and precision of quantitation. Repeatability and reproducibility are two essential requirements for any quantitative measurement and/or imaging biomarker. Repeatability relates to the uncertainty in obtaining the same result in the same patient when he or she is examined more than once on the same system. However, imaging biomarkers should also have adequate reproducibility, i.e. the ability to yield the same result in the same patient when that patient is examined on different systems and at different imaging sites. Adequate repeatability and reproducibility are essential for the clinical management of patients and the use of FDG PET/CT within multicentre trials. A common standardised imaging procedure will help promote the appropriate use of FDG PET/CT imaging and increase the value of publications and, therefore, their contribution to evidence-based medicine. Moreover, consistency in numerical values between platforms and institutes that acquire the data will potentially enhance the role of semiquantitative and quantitative image interpretation. Precision and accuracy are additionally important as FDG PET/CT is used to evaluate tumour response as well as for diagnosis, prognosis and staging. Therefore both the previous and these new guidelines specifically aim to achieve standardised uptake value harmonisation in multicentre settings.

PURPOSE: In light of recently published clinical reports and trials, the TheraSphere Global Dosimetry Steering Committee (DSC) reconvened to review new data and to update previously published clinical and dosimetric recommendations for the treatment of hepatocellular carcinoma (HCC). METHODS: The TheraSphere Global DSC is comprised of health care providers across multiple disciplines involved in the treatment of HCC with yttrium-90 (Y-90) glass microsphere-based transarterial radioembolization (TARE). Literature published between January 2019 and September 2021 was reviewed, discussed, and adjudicated by the Delphi method. Recommendations included in this updated document incorporate both the results of the literature review and the expert opinion and experience of members of the committee. RESULTS: Committee discussion and consensus led to the expansion of recommendations to apply to five common clinical scenarios in patients with HCC to support more individualized efficacious treatment with Y-90 glass microspheres. Existing clinical scenarios were updated to reflect recent developments in dosimetry approaches and broader treatment paradigms evolving for patients presenting with HCC. CONCLUSION: Updated consensus recommendations are provided to guide clinical and dosimetric approaches for the use of Y-90 glass microsphere TARE in HCC, accounting for disease presentation, tumor biology, and treatment intent.

PURPOSE: F-FDG tumour imaging was explored in the current study. Additional tests at various locations throughout the LAFOV and the use of shorter scan durations were included. Furthermore, clinical data were collected to further explore and validate the effects of reducing scan duration on semi-quantitative PET image biomarker accuracy and precision when using EARL-compliant reconstruction settings. METHODS: between scan durations. The coefficient of variation (COV) was calculated to characterise noise. RESULTS: between scan durations. Here, COV only varied slightly. CONCLUSION: Images obtained using the Vision Quadra PET/CT comply with EARL specifications. Scan duration and/or activity administration can be reduced up to a factor tenfold without the interference of increased noise.

The EC Directive 2013/59/Euratom states in article 56 that exposures of target volumes in nuclear medicine treatments shall be individually planned and their delivery appropriately verified. The Directive also mentions that medical physics experts should always be appropriately involved in those treatments. Although it is obvious that, in nuclear medicine practice, every nuclear medicine physician and physicist should follow national rules and legislation, the EANM considered it necessary to provide guidance on how to interpret the Directive statements for nuclear medicine treatments.For this purpose, the EANM proposes to distinguish three levels in compliance to the optimization principle in the directive, inspired by the indication of levels in prescribing, recording and reporting of absorbed doses after radiotherapy defined by the International Commission on Radiation Units and Measurements (ICRU): Most nuclear medicine treatments currently applied in Europe are standardized. The minimum requirement for those treatments is ICRU level 1 ("activity-based prescription and patient-averaged dosimetry"), which is defined by administering the activity within 10% of the intended activity, typically according to the package insert or to the respective EANM guidelines, followed by verification of the therapy delivery, if applicable. Non-standardized treatments are essentially those in developmental phase or approved radiopharmaceuticals being used off-label with significantly (> 25% more than in the label) higher activities. These treatments should comply with ICRU level 2 ("activity-based prescription and patient-specific dosimetry"), which implies recording and reporting of the absorbed dose to organs at risk and optionally the absorbed dose to treatment regions. The EANM strongly encourages to foster research that eventually leads to treatment planning according to ICRU level 3 ("dosimetry-guided patient-specific prescription and verification"), whenever possible and relevant. Evidence for superiority of therapy prescription on basis of patient-specific dosimetry has not been obtained. However, the authors believe that a better understanding of therapy dosimetry, i.e. how much and where the energy is delivered, and radiobiology, i.e. radiation-related processes in tissues, are keys to the long-term improvement of our treatments.

These joint practice guidelines, or procedure standards, were developed collaboratively by the European Association of Nuclear Medicine (EANM), the Society of Nuclear Medicine and Molecular Imaging (SNMMI), the European Association of Neurooncology (EANO), and the working group for Response Assessment in Neurooncology with PET (PET-RANO). Brain PET imaging is being increasingly used to supplement MRI in the clinical management of glioma. The aim of these standards/guidelines is to assist nuclear medicine practitioners in recommending, performing, interpreting and reporting the results of brain PET imaging in patients with glioma to achieve a high-quality imaging standard for PET using FDG and the radiolabelled amino acids MET, FET and FDOPA. This will help promote the appropriate use of PET imaging and contribute to evidence-based medicine that may improve the diagnostic impact of this technique in neurooncological practice. The present document replaces a former version of the guidelines published in 2006 (Vander Borght et al. Eur J Nucl Med Mol Imaging. 33:1374-80, 2006), and supplements a recent evidence-based recommendation by the PET-RANO working group and EANO on the clinical use of PET imaging in patients with glioma (Albert et al. Neuro Oncol. 18:1199-208, 2016). The information provided should be taken in the context of local conditions and regulations.

While the first time-of-flight (TOF)-positron emission tomography (PET) systems were already built in the early 1980s, limited clinical studies were acquired on these scanners. PET was still a research tool, and the available TOF-PET systems were experimental. Due to a combination of low stopping power and limited spatial resolution (caused by limited light output of the scintillators), these systems could not compete with bismuth germanate (BGO)-based PET scanners. Developments on TOF system were limited for about a decade but started again around 2000. The combination of fast photomultipliers, scintillators with high density, modern electronics, and faster computing power for image reconstruction have made it possible to introduce this principle in clinical TOF-PET systems. This paper reviews recent developments in system design, image reconstruction, corrections, and the potential in new applications for TOF-PET. After explaining the basic principles of time-of-flight, the difficulties in detector technology and electronics to obtain a good and stable timing resolution are shortly explained. The available clinical systems and prototypes under development are described in detail. The development of this type of PET scanner also requires modified image reconstruction with accurate modeling and correction methods. The additional dimension introduced by the time difference motivates a shift from sinogram- to listmode-based reconstruction. This reconstruction is however rather slow and therefore rebinning techniques specific for TOF data have been proposed. The main motivation for TOF-PET remains the large potential for image quality improvement and more accurate quantification for a given number of counts. The gain is related to the ratio of object size and spatial extent of the TOF kernel and is therefore particularly relevant for heavy patients, where image quality degrades significantly due to increased attenuation (low counts) and high scatter fractions. The original calculations for the gain were based on analytical methods. Recent publications for iterative reconstruction have shown that it is difficult to quantify TOF gain into one factor. The gain depends on the measured distribution, the location within the object, and the count rate. In a clinical situation, the gain can be used to either increase the standardized uptake value (SUV) or reduce the image acquisition time or administered dose. The localized nature of the TOF kernel makes it possible to utilize local tomography reconstruction or to separate emission from transmission data. The introduction of TOF also improves the joint estimation of transmission and emission images from emission data only. TOF is also interesting for new applications of PET-like isotopes with low branching ratio for positron fraction. The local nature also reduces the need for fine angular sampling, which makes TOF interesting for limited angle situations like breast PET and online dose imaging in proton or hadron therapy. The aim of this review is to introduce the reader in an educational way into the topic of TOF-PET and to give an overview of the benefits and new opportunities in using this additional information.

to effectively treat cancer.

Quantitative positron emission tomography/computed tomography (PET/CT) can be used as diagnostic or prognostic tools (i.e. single measurement) or for therapy monitoring (i.e. longitudinal studies) in multicentre studies. Use of quantitative parameters, such as standardized uptake values (SUVs), metabolic active tumor volumes (MATVs) or total lesion glycolysis (TLG), in a multicenter setting requires that these parameters be comparable among patients and sites, regardless of the PET/CT system used. This review describes the motivations and the methodologies for quantitative PET/CT performance harmonization with emphasis on the EANM Research Ltd. (EARL) Fluorodeoxyglucose (FDG) PET/CT accreditation program, one of the international harmonization programs aiming at using FDG PET as a quantitative imaging biomarker. In addition, future accreditation initiatives will be discussed. The validation of the EARL accreditation program to harmonize SUVs and MATVs is described in a wide range of tumor types, with focus on therapy assessment using either the European Organization for Research and Treatment of Cancer (EORTC) criteria or PET Evaluation Response Criteria in Solid Tumors (PERCIST), as well as liver-based scales such as the Deauville score. Finally, also presented in this paper are the results from a survey across 51 EARL-accredited centers reporting how the program was implemented and its impact on daily routine and in clinical trials, harmonization of new metrics such as MATV and heterogeneity features.

569 Introduction: Attenuation correction (AC) and scatter correction (SC) is a required step to enable diagnostic and quantitative PET imaging. While this is most commonly performed utilizing a sequential CT acquisition for PET/CT imaging, there may still exist limitations, such as patient movement between PET and CT or concerns about ionizing radiation dose. Recent work has explored PET-only AC approaches [1] and more recently, artificial intelligence (AI)-based approaches have been proposed for the brain [2,3]. The goal of this study is to develop and evaluate a whole-body PET-only attenuation correction approach using such an AI approach. Specifically, we seek to convert non-attenuation corrected (NAC) PET images directly into AC and SC PET images using a convolutional neural network. Methods: A deep convolutional encoder-decoder (CED) network using the UNet structure with 50% dropout, batch normalization, and max pooling was implemented in Keras. Model parameters included: starting input channels=16, depth=3, optimizer=Adam(lr=1e-4), loss function=mean squared error, batch size=20, # of training epochs=500. 50 clinical FDG PET/CT datasets were retrospectively obtained under IRB approval of subjects scanned on a single scanner (Discovery 710, GE Healthcare). 40 subjects were used to train the model with a validation split of 20%. 10 training-naive subjects were used to evaluate the model. Input images were non-time-of-flight (non-TOF) NAC PET images with an output target of TOF AC PET images. All images were resampled to 3x3x3mm prior to training. Structural similarity index (SSIM), mean average error (MAE), percent error (%-error), absolute percent error (%-abserror) were calculated for pixels inside the body (air not included) as performance metrics. Results: In the 10 evaluation subjects, the performance measures for the AI-AC image compared to AC were: SSIM=0.9429±0.0339; MAE=121.4803±73.3756 Bq/cc; %-error=-0.9163±10.4934 %; %-abserror=28.2073±5.3542 %. Performance measures for the NAC image compared to AC were: SSIM=.8331±.0716; MAE=472.9379± 165.5215 Bq/cc; %-error=-87.1119±3.4715 %; %-abserror=87.1221±3.4679 %. Compared to a NAC image alone, it is feasible that the AI-AC approach could potentially provide feasible AC images when a CT is not available. Discussion/Conclusion: We have presented a preliminary demonstration of direct NAC to AC conversion using a convolutional neural network. While absolute percent error of the proposed approach is on the order of 30%, this represents an interesting new capability for using direct conversion of input data into corrected data. Note that the NAC images used also lacked time-of-flight and scatter correction, which must also be inherently learned by the network. Additional interesting features of this output include reasonable performance for average-sized patients in areas with high amounts of focal activity, such as the bladder. However, in patients of very large girth, the method can be challenged by significant central soft tissue-related attenuation and lack of signal in the originating NAC image. Thus future work is necessary to further improve this approach, including optimization of the deep learning network, input and output image reconstruction parameters (e.g., use of TOF NAC), and generalizability between agents and scanner hardware. Ultimately, it may be feasible to perform direct reconstruction including attenuation and scatter correction directly from PET sinogram data using AI approaches [4]. References:1) Berker, Li. (2016). Med Phys. 43(2). 2) Liu, Jang, Kijowski, et al. (2018). EJNMMI Physics. 5:24. 3) Hwang, Kim, Kang, et al. (2018). J Nucl Med. 59(10). 4) Zhu, Liu, Cauley et al. (2018). Nature 555(7697).

PURPOSE: This joint practice guideline or procedure standard was developed collaboratively by the European Association of Nuclear Medicine (EANM) and the Society of Nuclear Medicine and Molecular Imaging (SNMMI). The goal of this guideline is to assist nuclear medicine practitioners in recommending, performing, interpreting, and reporting the results of dopaminergic imaging in parkinsonian syndromes. METHODS: F]fluorodopa imaging in this setting are still lacking. CONCLUSION: All these emerging issues are addressed in the present procedural guidelines for dopaminergic imaging in parkinsonian syndromes.

UNLABELLED: MR-based attenuation correction is instrumental for integrated PET/MR imaging. It is generally achieved by segmenting MR images into a set of tissue classes with known attenuation properties (e.g., air, lung, bone, fat, soft tissue). Bone identification with MR imaging is, however, quite challenging, because of the low proton density and fast decay time of bone tissue. The clinical evaluation of a novel, recently published method for zero-echo-time (ZTE)-based MR bone depiction and segmentation in the head is presented here. METHODS: A new paradigm for MR imaging bone segmentation, based on proton density-weighted ZTE imaging, was disclosed earlier in 2014. In this study, we reviewed the bone maps obtained with this method on 15 clinical datasets acquired with a PET/CT/MR trimodality setup. The CT scans acquired for PET attenuation-correction purposes were used as reference for the evaluation. Quantitative measurements based on the Jaccard distance between ZTE and CT bone masks and qualitative scoring of anatomic accuracy by an experienced radiologist and nuclear medicine physician were performed. RESULTS: The average Jaccard distance between ZTE and CT bone masks evaluated over the entire head was 52% ± 6% (range, 38%-63%). When only the cranium was considered, the distance was 39% ± 4% (range, 32%-49%). These results surpass previously reported attempts with dual-echo ultrashort echo time, for which the Jaccard distance was in the 47%-79% range (parietal and nasal regions, respectively). Anatomically, the calvaria is consistently well segmented, with frequent but isolated voxel misclassifications. Air cavity walls and bone/fluid interfaces with high anatomic detail, such as the inner ear, remain a challenge. CONCLUSION: This is the first, to our knowledge, clinical evaluation of skull bone identification based on a ZTE sequence. The results suggest that proton density-weighted ZTE imaging is an efficient means of obtaining high-resolution maps of bone tissue with sufficient anatomic accuracy for, for example, PET attenuation correction.

BACKGROUND: The purpose of the study is to evaluate the physical performance of a Biograph mCT Flow 64-4R PET/CT system (Siemens Healthcare, Germany) and to compare clinical image quality in step-and-shoot (SS) and continuous table motion (CTM) acquisitions. METHODS: The spatial resolution, sensitivity, count rate curves, and Image Quality (IQ) parameters following the National Electrical Manufactures Association (NEMA) NU2-2012 standard were evaluated. For resolution measurements, an (18)F point source inside a glass capillary tube was used. Sensitivity measurements were based on a 70-cm-long polyethylene tube, filled with 4.5 MBq of FDG. Scatter fraction and count rates were measured using a 70-cm-long polyethylene cylinder with a diameter of 20 cm and a line source (1.04 GBq of FDG) inserted axially into the cylinder 4.5 cm off-centered. A NEMA IQ phantom containing six spheres (10- to 37-mm diameter) was used for the evaluation of the image quality. First, a single-bed scan was acquired (NEMA standard), followed by a two-bed scan (4 min each) of the IQ phantom with the image plane containing the spheres centered in the overlap region of the two bed positions. In addition, a scan of the same region in CTM mode was performed with a table speed of 0.6 mm/s. Furthermore, two patient scans were performed in CTM and SS mode. Image contrasts and patient images were compared between SS and CTM acquisitions. RESULTS: Full Width Half Maximum (FWHM) of the spatial resolution ranged from 4.3 to 7.8 mm (radial distance 1 to 20 cm). The measured sensitivity was 9.6 kcps/MBq, both at the center of the FOV and 10 cm off-center. The measured noise equivalent count rate (NECR) peak was 185 kcps at 29.0 kBq/ml. The scatter fraction was 33.5 %. Image contrast recovery values (sphere-to-background of 8:1) were between 42 % (10-mm sphere) to 79 % (37-mm sphere). The background variability was between 2.1 and 5.3 % (SS) and between 2.4 and 6.9 % (CTM). No significant difference in image quality was observed between SS and CTM mode. CONCLUSIONS: The spatial resolution, sensitivity, scatter fraction, and count rates were in concordance with the published values for the predecessor system, the Biograph mCT. Contrast recovery values as well as image quality obtained in SS and CTM acquisition modes were similar.