Yttrium-90 radioembolization ( 90 Y-RE) is a well-established therapy for the treatment of hepatocellular carcinoma (HCC) and also of metastatic liver deposits from other malignancies. Nuclear Medicine and Cath Lab diagnostic imaging takes a pivotal role in the success of the treatment, and in order to fully exploit the efficacy of the technique and provide reliable quantitative dosimetry that are related to clinical endpoints in the era of personalized medicine, technical challenges in imaging need to be overcome. In this paper, the extensive literature of current 90 Y-RE techniques and challenges facing it in terms of quantification and dosimetry are reviewed, with a focus on the current generation of 3D dosimetry techniques. Finally, new emerging techniques are reviewed which seek to overcome these challenges, such as highresolution imaging, novel surgical procedures and the use of other radiopharmaceuticals for therapy and pre-therapeutic planning.

AbstactObjectivesMyocardial blood flow (MBF) imaging is used in patients with suspected cardiac sarcoidosis, and also in stress/rest studies. The accuracy of MBF is dependent on imaging parameters such as new reconstruction methodologies. In this work, we aim to assess the impact of a novel PET reconstruction algorithm (Bayesian-penalized likelihood—BPL) on the values determined from the calculation of [13N]-NH3 MBF values.MethodsData from 21 patients undergoing rest MBF evaluation [13N]-NH3 as part of sarcoidosis imaging were retrospectively analyzed. Each scan was reconstructed with a range of BPL coefficients (1-500), and standard clinical FBP and OSEM reconstructions. MBF values were calculated via an automated software routine for all datasets.ResultsReconstruction of [13N]-NH3 dynamic data using the BPL, OSEM, or FBP reconstruction showed no quantitative differences for the calculation of territorial or global MBF (P = .97). Image noise was lower using OSEM or BPL reconstructions than FBP and noise from BPL reached levels seen in OSEM images between B = 300 and B = 400. Intrasubject differences between all reconstructions over all patients in respect of all cardiac territories showed a maximum coefficient of variation of 9.74%.ConclusionQuantitation of MBF via kinetic modeling of cardiac rest MBF by [13N]-NH3 is minimally affected by the use of a BPL reconstruction technique, with BPL images presenting with less noise.

BackgroundPET-MRI is under investigation as a new strategy for quantitative myocardial perfusion imaging. Consideration is required as to the maximum scanner count rate in order to limit dead-time losses resulting from administered activity in the scanner field of view during the first pass of the radiotracer.ResultsWe performed a decaying-source experiment to investigate the high count-rate performance of a PET-MR system (Siemens mMR) over the expected range of activities during a clinical study. We also performed imaging of a cardiac perfusion phantom, which provides an experimental simulation of clinical transit of a simultaneous radiotracer (phantom injected activities range 252 to 997 MBq) and gadolinium-based contrast agent (GBCA). Time-activity and time-intensity curves of the aorta and myocardium compartments from PET and MR images were determined, and quantification of perfusion was then performed using a standard cardiac kinetic model. The decaying-source experiment showed a maximum noise equivalent count rate (NECRmax) of 286 kcps at a singles rate of 47.1 Mcps. NECR was maintained within 5% (NECR95%) of the NECRmax with a singles rate of 34.1 Mcps, corresponding to 310 MBq in the phantom. Count-rate performance was degraded above the singles rate of 64.9 Mcps due to the number of detection events impacting the quantitative accuracy of reconstructed images. A 10% bias in image activity concentration was observed between singles rates of 78.2 and 82.9 Mcps. Perfusion phantom experiments showed that image-based activity concentration and quantified values of perfusion were affected by count losses when the total singles rate was greater than 64.9 Mcps. This occurred during the peak arterial input function (AIF) phase of imaging for injected activities to the phantom of 600 MBq and greater.ConclusionsCare should be taken to avoid high count-rate losses in simultaneous PET-MRI studies. Based on our results in phantoms, bias in reconstructed images should be avoided by adhering to a singles rate lower than 64.9 Mcps on the mMR system. Quantification of perfusion values using singles rates higher than 64.9 Mcps on this system may be compromised and should be avoided.

BackgroundSimultaneous cardiac perfusion studies are an increasing trend in PET-MR imaging. During dynamic PET imaging, the introduction of gadolinium-based MR contrast agents (GBCA) at high concentrations during a dual injection of GBCA and PET radiotracer may cause increased attenuation effects of the PET signal, and thus errors in quantification of PET images. We thus aimed to calculate the change in linear attenuation coefficient (LAC) of a mixture of PET radiotracer and increasing concentrations of GBCA in solution and furthermore, to investigate if this change in LAC produced a measurable effect on the image-based PET activity concentration when attenuation corrected by three different AC strategies.FindingsWe performed simultaneous PET-MR imaging of a phantom in a static scenario using a fixed activity of 40 MBq [18 F]-NaF, water, and an increasing GBCA concentration from 0 to 66 mM (based on an assumed maximum possible concentration of GBCA in the left ventricle in a clinical study). This simulated a range of clinical concentrations of GBCA. We investigated two methods to calculate the LAC of the solution mixture at 511 keV: (1) a mathematical mixture rule and (2) CT imaging of each concentration step and subsequent conversion to LAC at 511 keV. This comparison showed that the ranges of LAC produced by both methods are equivalent with an increase in LAC of the mixed solution of approximately 2% over the range of 0–66 mM.We then employed three different attenuation correction methods to the PET data: (1) each PET scan at a specific millimolar concentration of GBCA corrected by its corresponding CT scan, (2) each PET scan corrected by a CT scan with no GBCA present (i.e., at 0 mM GBCA), and (3) a manually generated attenuation map, whereby all CT voxels in the phantom at 0 mM were replaced by LAC = 0.1 cm−1. All attenuation correction methods (1–3) were accurate to the true measured activity concentration within 5%, and there were no trends in image-based activity concentrations upon increasing the GBCA concentration of the solution.ConclusionThe presence of high GBCA concentration (representing a worst-case scenario in dynamic cardiac studies) in solution with PET radiotracer produces a minimal effect on attenuation-corrected PET quantification.

Purpose Standardized uptake value ratio (SUVr) used to quantify amyloid-β burden from amyloid-PET scans can be biased by variations in the tracer’s nonspecific (NS) binding caused by the presence of cerebrovascular disease (CeVD). In this work, we propose a novel amyloid-PET quantification approach that harnesses the intermodal image translation capability of convolutional networks to remove this undesirable source of variability. Methods Paired MR and PET images exhibiting very low specific uptake were selected from a Singaporean amyloid-PET study involving 172 participants with different severities of CeVD. Two convolutional neural networks (CNN), ScaleNet and HighRes3DNet, and one conditional generative adversarial network (cGAN) were trained to map structural MR to NS PET images. NS estimates generated for all subjects using the most promising network were then subtracted from SUVr images to determine specific amyloid load only (SAβL). Associations of SAβL with various cognitive and functional test scores were then computed and compared to results using conventional SUVr. Results Multimodal ScaleNet outperformed other networks in predicting the NS content in cortical gray matter with a mean relative error below 2%. Compared to SUVr, SAβL showed increased association with cognitive and functional test scores by up to 67%. Conclusion Removing the undesirable NS uptake from the amyloid load measurement is possible using deep learning and substantially improves its accuracy. This novel analysis approach opens a new window of opportunity for improved data modeling in Alzheimer’s disease and for other neurodegenerative diseases that utilize PET imaging.

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Background: Arterial sampling in PET studies for the purposes of kinetic modeling remains an invasive, time-intensive, and expensive procedure. Alternatives to derive the blood time-activity curve (BTAC) non-invasively are either reliant on large vessels in the field of view or are laborious to implement and analyze as well as being prone to many processing errors. An alternative method is proposed in this work by the simulation of a non-invasive coincidence detection unit. Results: We utilized GATE simulations of a human forearm phantom with a blood flow model, as well as a model for dynamic radioactive bolus activity concentration based on clinical measurements. A fixed configuration of 14 and, also separately, 8 detectors were employed around the phantom, and simulations were performed to investigate signal detection parameters. Bismuth germanate (BGO) crystals proved to show the highest count rate capability and sensitivity to a simulated BTAC with a maximum coincidence rate of 575 cps. Repeatable location of the blood vessels in the forearm allowed a half-ring design with only 8 detectors. Using this configuration, maximum coincident rates of 250 cps and 42 cps were achieved with simulation of activity concentration determined from 15 O and 18 F arterial blood sampling. NECR simulated in a water phantom at 3 different vertical positions inside the 8-detector system (Y = − 1 cm, Y = − 2 cm, and Y = −3 cm) was 8360 cps, 13,041 cps, and 20,476 cps at an activity of 3.5 MBq. Addition of extra axial detection rings to the half-ring configuration provided increases in system sensitivity by a factor of approximately 10. Conclusions: Initial simulations demonstrated that the configuration of a single halfring 8 detector of monolithic BGO crystals could describe the simulated BTAC in a clinically relevant forearm phantom with good signal properties, and an increased number of axial detection rings can provide increased sensitivity of the system. The system would find use in the derivation of the BTAC for use in the application of kinetic models without physical arterial sampling or reliance on image-based techniques.

In light of widely expanding personalized medicine applications and their impact on clinical outcomes, it is naturally befitting to explore all the dimensional aspects of personalized radionuclide therapy (RNT). Adoption of absorbed radiation dose into clinical practice in the field of RNT has been hampered by difficulties such as evidence of dose-effect correlation, technical requirements in quantitative imaging of the radiopharmaceutical, heterogeneity of methods between not only centers, but also across software, hardware and radionuclides used. Additionally, standardized agreed upon definition of outcome measures is being debated whether it be solely related to toxicity, quality of life, survival or other measures. Many clinical RNT activity administrations are still based on empirical/fixed activities, or scaled based on parameters such as body surface area. Although still challenging, a tremendous amount of progress has been made to facilitate routine clinical dosimetry with discussions regarding standardization, harmonization and automated processing techniques. This has also been aided by the development and FDA approval of several companion diagnostics allowing within the theranostic paradigm not only a crude qualitative predictive biomarker but also an objective dosimetry based predictive therapeutic biomarker. This work aims to review the literature of [177Lu]Lu-PSMA RNT, focusing on clinical trials and studies, with the goal to summarize the range of dosimetry techniques and the range of doses calculated to organs and tissues of interest from these techniques. A dosimetry method for [177Lu]Lu-PSMA RNT should be reliable, reproducible and encompassing the knowledge gained from all clinical trials evaluating it. Its translation into clinical routine practice can be achieved with the confirmation that dose calculation represents good clinical efficacy and low treatment-related toxicity. Finally, some future perspectives on the future of [177Lu]Lu-PSMA RNT are made, especially in the rapidly emerging field of artificial intelligence (AI), where deep learning may be able to play a large role in the simplification of dosimetry calculations to aid in their clinical adoption.