Search

Purpose Performing 2-[18F]FDG PET/CT in addition to a PSMA-ligand PET/CT can assist in the detection of lesions with low PSMA expression and may help in prognostication and identification of patients who likely benefit from PSMA-radioligand therapy (PSMA-RLT). However, the cost and time needed for a separate PET/CT examination might hinder its routine implementation. In this communication, we present our initial experiences with additional low-dose 2-[18F]FDG PET/CT as part of a dual-tracer and same-day imaging protocol which exploits the higher sensitivity exhibited by long-axial field-of-view (LAFOV) and total-body PET/CT systems and demonstrates its feasibility. Methods Fourteen patients referred for evaluation for PSMA-RLT received [68 Ga]Ga-PSMA-11 PET/CT at 1 h p.i. with a standard activity of 150 MBq and an additional low-dose 2-[18F]FDG PET/CT with 40 MBq 1 h thereafter using a long-axial field-of-view PET/CT system in a single sitting and as per institutional protocol. Scans were scrutinized by two experienced nuclear medicine physicians for mismatch findings. Results The combined protocol identified additional lesions with low or absent PSMA-expression but high FDG-avidity in 1/14 (7%) patients. The protocol was easily implemented and well tolerated by all patients. Conclusion Additional low-dose 2-[18F]FDG-PET/CT is feasible as part of a same-day imaging protocol and can help reveal lesions of low PSMA avidity as part of therapy assessment for [177Lu]-PSMA radioligand therapy and demonstrates higher sensitivity compared to [68 Ga]Ga-PSMA-11 PET/CT alone in some patients.

Background Accurate kinetic modeling of 18F-fluorodeoxyglucose ([18F]-FDG) positron emission tomography (PET) data requires accurate knowledge of the available tracer concentration in the plasma during the scan time, known as the arterial input function (AIF). The gold standard method to derive the AIF requires collection of serial arterial blood samples, but the introduction of long axial field of view (LAFOV) PET systems enables the use of non-invasive image-derived input functions (IDIFs) from large blood pools such as the aorta without any need for bed movement. However, such protocols require a prolonged dynamic PET acquisition, which is impractical in a busy clinical setting. Population-based input functions (PBIFs) have previously shown potential in accurate Patlak analysis of [18F]-FDG datasets and can enable the use of shortened dynamic imaging protocols. Here, we exploit the high sensitivity and temporal resolution of a LAFOV PET system and explore the use of PBIF with abbreviated protocols in [18F]-FDG total body kinetic modeling. Methods Dynamic PET data were acquired in 24 oncological subjects for 65 min following the administration of [18F]-FDG. IDIFs were extracted from the descending thoracic aorta, and a PBIF was generated from 16 datasets. Five different scaled PBIFs (sPBIFs) were generated by scaling the PBIF with the AUC of IDIF curve tails using various portions of image data (35–65, 40–65, 45–65, 50–65, and 55–65 min post-injection). The sPBIFs were compared with the IDIFs using the AUCs and Patlak Ki estimates in tumor lesions and cerebral gray matter. Patlak plot start time (t*) was also varied to evaluate the performance of shorter acquisitions on the accuracy of Patlak Ki estimates. Patlak Ki estimates with IDIF and t* = 35 min were used as reference, and mean bias and precision (standard deviation of bias) were calculated to assess the relative performance of different sPBIFs. A comparison of parametric images generated using IDIF and sPBIFs was also performed. Results There was no statistically significant difference between AUCs of the IDIF and sPBIFs (Wilcoxon test: P > 0.05). Excellent agreement was shown between Patlak Ki estimates obtained using sPBIF and IDIF. Using the sPBIF55–65 with the Patlak model, 20 min of PET data (i.e., 45 to 65 min post-injection) achieved Ki estimates in tumor lesions compared to the estimates with the IDIF. Parametric images reconstructed using the IDIF and sPBIFs with and without an abbreviated protocol were visually comparable. Using Patlak Ki generated with an IDIF and 30 min of PET data as reference, Patlak Ki images generated using sPBIF55–65 with 20 min of PET data (t* = 45 min) provided excellent image quality with structural similarity index measure > 0.99 and peak signal-to-noise ratio > 55 dB. Conclusion We demonstrate the feasibility of performing accurate [18F]-FDG Patlak analysis using sPBIFs with only 20 min of PET data from a LAFOV PET scanner.

Recently introduced long-axial field-of-view (LAFOV) PET/CT systems represent one of the most significant advancements in nuclear medicine since the advent of multi-modality PET/CT imaging. The higher sensitivity exhibited by such systems allow for reductions in applied activity and short duration scans. However, we consider this to be just one small part of the story: Instead, the ability to image the body in its entirety in a single FOV affords insights which standard FOV systems cannot provide. For example, we now have the ability to capture a wider dynamic range of a tracer by imaging it over multiple half-lives without detrimental image noise, to leverage lower radiopharmaceutical doses by using dual-tracer techniques and with improved quantification. The potential for quantitative dynamic whole-body imaging using abbreviated protocols potentially makes these techniques viable for routine clinical use, transforming PET-reporting from a subjective analysis of semi-quantitative maps of radiopharmaceutical uptake at a single time-point to an accurate and quantitative, non-invasive tool to determine human function and physiology and to explore organ interactions and to perform whole-body systems analysis. This article will share the insights obtained from 2 years’ of clinical operation of the first Biograph Vision Quadra (Siemens Healthineers) LAFOV system. It will also survey the current state-of-the-art in PET technology. Several technologies are poised to furnish systems with even greater sensitivity and resolution than current systems, potentially with orders of magnitude higher sensitivity. Current barriers which remain to be surmounted, such as data pipelines, patient throughput and the hindrances to implementing kinetic analysis for routine patient care will also be discussed.

Background We aimed to compare coronary artery calcium scoring (CACS) with computed tomography (CT) with 80 and 120 kVp in a large patient population and to establish whether there is a difference in risk classification between the two scores. Methods Patients with suspected CAD undergoing MPS were included. All underwent standard CACS assessment with 120-kVp tube voltage and with 80 kVp. Two datasets (low-dose and standard) were generated and compared. Risk classes (0 to 25, 25 to 50, 50 to 75, 75 to 90, and > 90%) were recorded. Results 1511 patients were included (793 males, age 69 ± 9.1 years). There was a very good correlation between scores calculated with 120 and 80 kVp (R = 0.94, R2 = 0.88, P P = .03) and with CACS = 0 differed between the two protocols (n = 264 vs 437, P Conclusion In a large patient population, despite a good correlation between CACS calculated with standard and low-dose CT, there is a systematic underestimation of CACS with the low-dose protocol. This may have an impact especially on the prognostic value of the calcium score, and the established “power of zero” may no longer be warranted if CACS is assessed with low-dose CT.

The non-invasive quantification of the cerebral metabolic rate for glucose (CMRGlc) and the characterization of cerebral metabolism in the cerebrovascular territories are helpful in understanding ischemic cerebrovascular disease (ICVD). Firstly, we investigated a non-invasive quantification approach based on an image-derived input function (IDIF) in ICVD. Second, we studied the metabolic changes in CMRGlc after surgical intervention. We evaluated the hypothesis that the IDIF method based on the unilateral internal carotid artery could address challenges in ICVD quantification. The CMRGlc and standardized uptake value ratio (SUVR) were used to measure glucose metabolism activity. Healthy controls showed no significant differences in CMRGlc values between bilateral and unilateral IDIF measurements (intraclass correlation coefficient [ICC]: 0.91-0.98). Patients with ICVD showed significantly increased CMRGlc values after surgical intervention for all territories (percentage changes: 7.4%-22.5%). In contrast, SUVR showed minor differences between postoperative and preoperative patients, indicating that it was a poor biomarker for the diagnosis of ICVD. A significant association between CMRGlc and the National Institutes of Health Stroke Scale (NIHSS) scores was observed (r=-0.54). Our findings suggested that IDIF could be a valuable tool for CMRGlc quantification in patients with ICVD and may advance personalized precision interventions.

Background A number of radiopharmaceuticals are available for the detection of recurrent prostate cancer (rPC), but few comparative imaging trials have been performed comparing them. In particular, there are no prospective head-to-head comparisons of the recently introduced [18F]PSMA-1007 to the existing standard of care [68Ga]Ga-PSMA-11. The purpose of this trial is to establish the non-inferiority of the new radiopharmaceutical in terms of the rate of PET-positive findings and to obtain an intra-individual comparison of accuracy and radiopharmaceutical kinetics. Methods In this cross-over trial we will randomise 100 individuals to receive either first a standard-of-care PET/CT using [68Ga]Ga-PSMA-11 followed by an additional [18F]PSMA-1007 PET/CT within 2 weeks, or vice-versa. Inclusion criteria include patients 18 years and older with biochemical recurrence of prostate cancer following radical prostatectomy, defined as two consecutive prostate specific antigen (PSA) levels > 0.2 ng/ml. Detection rate at the patient-based level is the primary end-point. Each scan will be interpreted by a panel of six independent and masked readers (three for [68Ga]Ga-PSMA-11 and three for [18F]PSMA-1007) which consensus majority in cases of discrepancy. To confirm the PET-positivity rate at a patient based level, follow up at 6 months following the first scan will be performed to a composite standard of truth. Secondary endpoints shall include an intra-individual comparison of radiopharmaceutical-kinetics, per-region detection rate and positive predictive value. Discussion This is the first randomised prospective comparative imaging trial to compare the established [68Ga]Ga-PSMA-11 with [18F]PSMA-1007 and will determine whether the new radiopharmaceutical is non-inferior to the established standard-of-care in terms of patient-level detection rate. Clinical trial registration Registered with and approved by the regional ethics authority #2020–02903 (submitted 09.12.2020, approval 16.12.2021) and the regulatory authority SwissMedic 2020DR2103. Registered with ClinicalTrials.gov Identifier NCT05079828 and additionally in a national language in the Swiss National Clinical Trials Portal (SNCTP).

Purpose While acquisition of images in [68 Ga]Ga-PSMA-11 following longer uptake times can improve lesion uptake and contrast, resultant imaging quality and count statistics are limited by the isotope’s half-life (68 min). Here, we present a series of cases demonstrating that when performed using a long axial field-of-view (LAFOV) PET/CT system, late imaging is feasible and can even provide improved image quality compared to regular acquisitions. Methods In this retrospective case series, we report our initial experiences with 10 patients who underwent standard imaging at 1 h p.i. following administration of 192 ± 36 MBq [68 Ga]Ga-PSMA-11 with additional late imaging performed at 4 h p.i. Images were acquired in a single bed position for 6 min at 1 h p.i. and 16 min p.i. at 4 h p.i. using a LAFOV scanner (106 cm axial FOV). Two experienced nuclear medicine physicians reviewed all scans in consensus and evaluated overall image quality (5-point Likert scale), lesion uptake in terms of standardised uptake values (SUV), tumour to background ratio (TBR) and target-lesion signal to background noise (SNR). Results Subjective image quality as rated on a 5-point Likert scale was only modestly lower for late acquisitions (4.2/5 at 4 h p.i.; 5/5 1 h p.i.), TBR was significantly improved (4 h: 3.41 vs 1 h: 1.93, p p = 0.062) at later imaging. Images were obtained with total acquisition times comparable to routine examinations on standard axial FOV scanners. Conclusion Late acquisition in tandem with a LAFOV PET/CT resulted in improvements in TBR and SNR and was associated with only modest impairment in subjective visual imaging quality. These data show that later acquisition times for [68 Ga]Ga-PSMA-11 may be preferable when performed on LAFOV systems.

Purpose Attenuation correction is a critically important step in data correction in positron emission tomography (PET) image formation. The current standard method involves conversion of Hounsfield units from a computed tomography (CT) image to construct attenuation maps (µ-maps) at 511 keV. In this work, the increased sensitivity of long axial field-of-view (LAFOV) PET scanners was exploited to develop and evaluate a deep learning (DL) and joint reconstruction-based method to generate µ-maps utilizing background radiation from lutetium-based (LSO) scintillators. Methods Data from 18 subjects were used to train convolutional neural networks to enhance initial µ-maps generated using joint activity and attenuation reconstruction algorithm (MLACF) with transmission data from LSO background radiation acquired before and after the administration of 18F-fluorodeoxyglucose (18F-FDG) (µ-mapMLACF-PRE and µ-mapMLACF-POST respectively). The deep learning-enhanced µ-maps (µ-mapDL-MLACF-PRE and µ-mapDL-MLACF-POST) were compared against MLACF-derived and CT-based maps (µ-mapCT). The performance of the method was also evaluated by assessing PET images reconstructed using each µ-map and computing volume-of-interest based standard uptake value measurements and percentage relative mean error (rME) and relative mean absolute error (rMAE) relative to CT-based method. Results No statistically significant difference was observed in rME values for µ-mapDL-MLACF-PRE and µ-mapDL-MLACF-POST both in fat-based and water-based soft tissue as well as bones, suggesting that presence of the radiopharmaceutical activity in the body had negligible effects on the resulting µ-maps. The rMAE values µ-mapDL-MLACF-POST were reduced by a factor of 3.3 in average compared to the rMAE of µ-mapMLACF-POST. Similarly, the average rMAE values of PET images reconstructed using µ-mapDL-MLACF-POST (PETDL-MLACF-POST) were 2.6 times smaller than the average rMAE values of PET images reconstructed using µ-mapMLACF-POST. The mean absolute errors in SUV values of PETDL-MLACF-POST compared to PETCT were less than 5% in healthy organs, less than 7% in brain grey matter and 4.3% for all tumours combined. Conclusion We describe a deep learning-based method to accurately generate µ-maps from PET emission data and LSO background radiation, enabling CT-free attenuation and scatter correction in LAFOV PET scanners.

The clinical presentations of early idiopathic Parkinson disease (IPD) substantially overlap with those of atypical parkinsonian syndromes such as multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). This study aimed to develop metabolic imaging indices based on deep learning to support the differential diagnosis of these conditions. Methods: A benchmark Huashan parkinsonian PET imaging (HPPI, China) database including 1,275 parkinsonian patients and 863 nonparkinsonian subjects with (18)F-FDG PET images was established to support artificial intelligence development. A 3-dimensional deep convolutional neural network was developed to extract deep metabolic imaging (DMI) indices and blindly evaluated in an independent cohort with longitudinal follow-up from the HPPI and an external German cohort of 90 parkinsonian patients with different imaging acquisition protocols. Results: The proposed DMI indices had less ambiguity space in the differential diagnosis. They achieved sensitivities of 98.1%, 88.5%, and 84.5%, and specificities of 90.0%, 99.2%, and 97.8%, respectively, for the diagnosis of IPD, MSA, and PSP in the blind-test cohort. In the German cohort, they resulted in sensitivities of 94.1%, 82.4%, and 82.1%, and specificities of 84.0%, 99.9%, and 94.1%, respectively. Using the PET scans independently achieved a performance comparable to the integration of demographic and clinical information into the DMI indices. Conclusion: The DMI indices developed on the HPPI database show the potential to provide an early and accurate differential diagnosis for parkinsonism and are robust when dealing with discrepancies between populations and imaging acquisitions.

Aim Despite increasing use for the detection of biochemically recurrent prostate cancer (rPC), the diagnostic accuracy of positron emission tomography/computed tomography (PET/CT) with [18F]PSMA-1007 remains only partially investigated. The aim of this study was to determine the sensitivity (SE), specificity (SP), positive predictive value (PPV), and negative predictive value (NPV) for PC-local recurrence and metastases on a per region basis. Materials and methods One hundred seventy-seven consecutive patients undergoing [18F]PSMA-1007 PET/CT for rPC were retrospectively analysed. Six body regions were defined: prostate fossa, pelvic lymph nodes (LN), retroperitoneal LN, supradiaphragmatic LN, bones, and soft tissue. A region was counted positive if at least one PSMA-positive lesion suspicious for PC was observed. Confirmation of a true-positive PSMA-avid lesion was defined as positive by histopathology, fall in serum prostate-specific antigen (PSA) (> 50%) after targeted therapy or confirmatory further CT, MRI, PET/CT, or bone scan imaging. Regions where additional imaging was able to confirm the absence of suspicious PC lesions or regions outside exclusively targeted RT with serum PSA decline (> 50%) were counted as true-negative regions. SE, SP, PPV, and NPV were calculated for all six regions. Results The overall PET-positivity rate was 91%. Conclusive follow-up for affirmation or refutation of a PSMA-positive lesion was available for 81/152 patients on a per region basis. In this subgroup, overall sensitivity, specificity, PPV, and NPV were 95% (CI: 0.90–0.98), 89% (CI: 0.83–0.93), 86% (0.80–0.90), and 96% (CI: 0.92–0.98), respectively. On a per region basis, PPV was 97% (CI: 0.83–0.99) for local recurrence, 93% (CI: 0.78–0.98) for pelvic LN, 87% (CI: 0.62–0.96) for retroperitoneal LN, 82% (CI: 0.52–0.95) for supradiaphragmatic LN, and 79% (0.65–0.89) for bone lesions. The number of solid organ metastases (n = 6) was too small for an accurate statistical analysis. Conclusion The known high PET-positivity rate of [18F]PSMA-1007 PET/CT in rPC was confirmed, with corresponding high (> 90%) sensitivity and NPV on a per region basis. However, overall PPV was limited (86%), particularly for bone lesions (79%), which are a potential diagnostic weaknesses when using this tracer.

PURPOSE Kinetic parameters from dynamic 18F-fluorodeoxyglucose (FDG) imaging offer complementary insights to the study of disease compared to static clinical imaging. However, dynamic imaging protocols are cumbersome due to the long acquisition time. Long axial field-of-view (LAFOV) PET scanners (>���70��cm) have two advantages for dynamic imaging over clinical PET scanners with a standard axial field-of-view (SAFOV; 16-30��cm). The large axial coverage enables multi-organ dynamic imaging in a single bed position, and the high sensitivity may enable clinically routine abbreviated dynamic imaging protocols. METHODS In this work, we studied two abbreviated protocols using data from a 65-min dynamic 18F-FDG scan: (A) dynamic imaging immediately post-injection (p.i.) for variable durations, and (B) dynamic imaging immediately p.i. for variable durations plus a 1-h p.i. (5-min-long) datapoint. Nine cancer patients were imaged on the Biograph Vision Quadra (Siemens Healthineers). Time-activity curves over the lesions (N���=���39) were fitted using the Patlak graphical analysis and a 2-tissue-compartment (2C, k4���=���0) model for variable scan durations (5-60��min). Kinetic parameters from the complete dataset served as the reference. Lesions from all cancers were grouped into low, medium, and high flux groups, and bias and precision of Ki (Patlak) and Ki, K1, k2, and k3 (2C) were calculated for each group. RESULTS Using only early dynamic data with the 2C (or Patlak) model, accurate quantification of Ki required at least 50 (or 55) min of dynamic data for low flux lesions, at least 30 (or 40) min for medium flux lesions, and at least 15 (or 20) min for high flux lesions to achieve both 10% bias and precision. The addition of the final (5-min) datapoint allowed for accurate quantification of Ki with a bias and precision of 10% using only 10-15��min of early dynamic data for either model. CONCLUSION Dynamic imaging for 10-15��min immediately p.i. followed by a 5-min scan at 1-h p.i can accurately and precisely quantify 18F-FDG on a long axial FOV scanner, potentially allowing for more widespread use of dynamic 18F-FDG imaging.

Background Systemic inflammation is predictive of the overall survival in cancer patients and is related to the density of immune cells in the tumor microenvironment of cancer, which in turn correlates with 18F -fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography (PET/CT) metabolic parameters (MPs). The density of tumor-infiltrating lymphocytes (TILs) in the microenvironment has the potential to be a biomarker that can be used clinically to optimize patient selection in oropharyngeal head and neck squamous cell carcinoma (HNSCC). There is little to no data regarding the association of systemic inflammation with PET/CT-MPs, especially in HNSCC. This study aimed to evaluate the correlation between markers of host inflammation, namely blood neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), with the PET/CT-MPs standardized uptake value (SUV), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumor, derived from FDG-PET/CT in patients with nonmetastatic (cM0) HNSCC before treatment. We hypothesized that NLR and PLR at baseline are positively correlated with PET/CT-MPs. Methods A retrospective review of consecutive patients with HNSCC with a pretreatment PET/CT was performed. NLR and PLR were computed using complete blood counts measured within 10 days before the start of any treatment. The correlation between NLR and PLR with PET/CT-MPs was evaluated with Spearman's rho test. Results Seventy-one patients were analyzed. Overall survival (OS) at 1, 2, and 3 years was 86%, 76%, and 68%. PLR was found to be correlated with MTV (rho = 0.26, P = .03) and TLG (rho = 0.28, P = .02) but not with maximum SUV or mean SUV. There was no correlation between NLR and the analyzed PET/CT-MPs. TLG was associated with worse survival in uni- and multivariable analysis, but no other PET/CT-MPs were associated with either OS or disease-specific survival (DSS). NLR and PLR were associated with OS and DSS on uni- and multivariable analysis. Conclusions In patients with HNSCC before any treatment such as definitive radio (chemo)therapy or oncologic surgery followed by adjuvant RT, baseline PLR correlated with MTV and TLG but not with SUV. NLR was not correlated with any PET/CT-MPs analyzed in our study. Confirmatory studies are needed, and a potential interaction between tumor microenvironment, host inflammation, and FDG-PET/CT measures warrants further investigation.

Purpose Alzheimer’s disease (AD) studies revealed that abnormal deposition of tau spreads in a specific spatial pattern, namely Braak stage. However, Braak staging is based on post mortem brains, each of which represents the cross section of the tau trajectory in disease progression, and numerous studies were reported that do not conform to that model. This study thus aimed to identify the tau trajectory and quantify the tau progression in a data-driven approach with the continuous latent space learned by variational autoencoder (VAE). Methods A total of 1080 [18F]Flortaucipir brain positron emission tomography (PET) images were collected from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. VAE was built to compress the hidden features from tau images in latent space. Hierarchical agglomerative clustering and minimum spanning tree (MST) were applied to organize the features and calibrate them to the tau progression, thus deriving pseudo-time. The image-level tau trajectory was inferred by continuously sampling across the calibrated latent features. We assessed the pseudo-time with regard to tau standardized uptake value ratio (SUVr) in AD-vulnerable regions, amyloid deposit, glucose metabolism, cognitive scores, and clinical diagnosis. Results We identified four clusters that plausibly capture certain stages of AD and organized the clusters in the latent space. The inferred tau trajectory agreed with the Braak staging. According to the derived pseudo-time, tau first deposits in the parahippocampal and amygdala, and then spreads to the fusiform, inferior temporal lobe, and posterior cingulate. Prior to the regional tau deposition, amyloid accumulates first. Conclusion The spatiotemporal trajectory of tau progression inferred in this study was consistent with Braak staging. The profile of other biomarkers in disease progression agreed well with previous findings. We addressed that this approach additionally has the potential to quantify tau progression as a continuous variable by taking a whole-brain tau image into account.

Predicting the risk of disease progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD) has important clinical significance. This study aimed to provide a personalized MCI-to-AD conversion prediction via radiomics-based predictive modelling (RPM) with multicenter 18F-fluorodeoxyglucose positron emission tomography (FDG PET) data.FDG PET and neuropsychological data of 884 subjects were collected from Huashan Hospital, Xuanwu Hospital, and from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. First, 34,400 radiomic features were extracted from the 80 regions of interest (ROIs) for all PET images. These features were then concatenated for feature selection, and an RPM model was constructed and validated on the ADNI dataset. In addition, we used clinical data and the routine semiquantification index (standard uptake value ratio, SUVR) to establish clinical and SUVR Cox models for further comparison. FDG images from local hospitals were used to explore RPM performance in a separate cohort of individuals with healthy controls and different cognitive levels (a complete AD continuum). Finally, correlation analysis was conducted between the radiomic biomarkers and neuropsychological assessments.The experimental results showed that the predictive performance of the RPM Cox model was better than that of other Cox models. In the validation dataset, Harrell's consistency coefficient of the RPM model was 0.703 ± 0.002, while those of the clinical and SUVR models were 0.632 ± 0.006 and 0.683 ± 0.009, respectively. Moreover, most crucial imaging biomarkers were significantly different at different cognitive stages and significantly correlated with cognitive disease severity.The preliminary results demonstrated that the developed RPM approach has the potential to monitor progression in high-risk populations with AD.

Purpose Many radiotracers are currently available for the detection of recurrent prostate cancer (rPC), yet many have not been compared head-to-head in comparative imaging studies. There is therefore an unmet need for evidence synthesis to guide evidence-based decisions in the selection of radiotracers. The objective of this study was therefore to assess the detection rate of various radiotracers for the rPC. Methods The PUBMED, EMBASE, and the EU and NIH trials databases were searched without date or language restriction for comparative imaging tracers for 13 radiotracers of principal interest. Key search terms included 18F-PSMA-1007, 18F-DCPFyl, 68Ga-PSMA-11, 18F-PSMA-11, 68Ga-PSMA-I&T, 68Ga-THP-PSMA, 64Cu-PSMA-617, 18F-JK-PSMA-7, 18F-Fluciclovine, 18F-FABC, 18F-Choline, 11C-Choline, and 68Ga-RM2. Studies reporting comparative imaging data in humans in rPC were selected. Single armed studies and matched pair analyses were excluded. Twelve studies with eight radiotracers were eligible for inclusion. Two independent reviewers screened all studies (using the PRISMA-NMA statement) for inclusion criteria, extracted data, and assessed risk of bias (using the QUADAS-2 tool). A network meta-analysis was performed using Markov-Chain Monte Carlo Bayesian analysis to obtain estimated detection rate odds ratios for each tracer combination. Results A majority of studies were judged to be at risk of publication bias. With the exception of 18F-PSMA-1007, little difference in terms of detection rate was revealed between the three most commonly used PSMA-radiotracers (68Ga-PSMA-11, 18F-PSMA-1007, 18F-DCFPyl), which in turn showed clear superiority to choline and fluciclovine using the derived network. Conclusion Differences in patient-level detection rates were observed between PSMA- and choline-radiotracers. However, there is currently insufficient evidence to favour one of the four routinely used PSMA-radioligands (PSMA-11, PSMA-1007, PSMA-I&T, and DCFPyl) over another owing to the limited evidence base and risk of publication bias revealed by our systematic review. A further limitation was lack of reporting on diagnostic accuracy, which might favour radiotracers with low specificity in an analysis restricted only to detection rate. The NMA derived can be used to inform the design of future clinical trials and highlight areas where current evidence is weak.

PURPOSE Digital PET/CT scanners represent a significant step forward in molecular imaging. We report here the clinical impact of digital PET in PSMA-PET/CT. METHODS In this retrospective study, 88 consecutive patients who underwent [68Ga]Ga-PSMA-11 PET/CT on a digital PET/CT (dPET/CT) scanner for recurrent prostate cancer (PC) were included in a first cohort. In a second step, 88 individuals who underwent an analogue [68Ga]Ga-PSMA-11 PET/CT (aPET/CT) were selected after they were matched to the first cohort for clinical parameters. Following consensus read by two nuclear medicine physicians, the number and type of PC lesions as well as benign, PSMA-positive lesions were recorded. The results were complemented by extensive [68Ga]Ga phantom measurements to determine imaging characteristics of both scanners. RESULTS dPET/CT revealed a greater number of PC lesions compared to aPET/CT (326 versus 142) as well as a proportional increase in benign causes of tracer-uptake (144 versus 65). A greater number of scans were noted as pathological for PC on dPET/CT (74/88) compared to aPET/CT (64/88, p < 0.05). The PSMA positivity rate for PC was significantly higher in dPET/CT for the lowest PSA values (PSA < 2.0 ng/ml, p < 0.05). CONCLUSION dPET/CT detected more PC lesions compared to aPET/CT. A significantly higher rate of pathological PET/CTs was noted in the group with the lowest PSA values. A higher number of benign PSMA-positive lesions were also noted in dPET/CT. The differences could be plausibly explained by the measured imaging characteristics of the scanners.

PURPOSE Dual-time point PET/CT scanning with [68Ga]Ga-PSMA-11 in the diagnosis of prostate cancer (PC) has been advanced as a method to increase detection of PC lesions, particularly at early stages of biochemical recurrence and as a potential means to aid the discrimination between benign and pathological prostate-specific membrane antigen (PSMA) uptake. However, the assumption that all PC lesions uniformly exhibit increasing tracer uptake at delayed imaging has not yet been investigated, which this present study aims to address. METHODS One hundred consecutive patients with biochemically recurrent PC who received standard and late [68Ga]Ga-PSMA-11 PET/CT (by local protocol at 1.5 h "standard" and 2.5 h p.i. "late") underwent retrospective evaluation. All lesions with a tracer uptake above local background were analysed with regard to their maximum standardised uptake values at standard and late images (SUVmax) and characterised according to their morphological characteristics. RESULTS Seventy-nine of 100 patients had PSMA-positive scans, in whom a total of 185 individual PSMA-positive lesions were identified. These were morphologically characterised as bone lesions (n = 48), solid organ lesions (n = 3), lymph node (LN) lesions (n = 78) and locally recurrent lesions in the prostatic fossa or seminal vesicles (n = 56). The relative uptake between standard and late imaging was considered; all lesions classified as local recurrence presented with increasing (86%) or stable patterns of tracer uptake (14%). In contrast, only 58% of bone lesions exhibited increasing tracer uptake, with 21% exhibiting a stable pattern and 21% exhibiting a decreasing tracer uptake at late imaging. CONCLUSION A heterogeneous pattern of dynamic tracer uptake was observed, with a largely increasing pattern observed for locally recurrent lesions and lymph nodes and a significant proportion of bone lesions exhibiting decreasing tracer uptake. The results are of significance not only in the imaging and identification of PC lesions, but they also have implications for PSMA-directed ligand therapy.

PURPOSE So far, there have been very few studies which provide a direct comparison between MRI and PSMA-ligand PET/CT for the detection of recurrent prostate cancer (rPC). This present study therefore aims to provide further clinical data in order to resolve this urgent clinical question, and thereby strengthen clinical recommendations. METHODS A retrospective analysis was performed for patients who were scanned at our institution with whole-body PSMA-PET/CT (tracer: 68Ga-PSMA-11) between January 2017 and September 2018 in order to detect rPC. Amongst them, 43 underwent an additional pelvic MRI within 2 months. Both modalities were compared as follows: a consensus read of the PET data was performed by two nuclear physicians. All lesions were recorded with respect to their type and localization. The same process was conducted by two radiologists for pelvic MRI. Thereafter, both modalities were directly compared for every patient and lesion. RESULTS Overall, 30/43 patients (69.8%) presented with a pathologic MRI and 38/43 (88.4%) with a pathologic PSMA-PET/CT of the pelvis. MRI detected 53 pelvic rPC lesions (13 of them classified as "uncertain") and PSMA-PET/CT detected 75 pelvic lesions (three classified as "uncertain"). The superiority of PSMA-PET/CT was statistically significant only if uncertain lesions were classified as false-positive. CONCLUSIONS PSMA-PET/CT detected more pelvic lesions characteristic for rPC when compared to MRI. In order to detect rPC, a potential future scenario could be conducting first a PSMA-PET/CT. Combining the advantages of both modalities in hybrid PET/MRI scanners would be an ideal future scenario.

Abstract Purpose A critical bottleneck for the credibility of artificial intelligence (AI) is replicating the results in the diversity of clinical practice. We aimed to develop an AI that can be independently applied to recover high-quality imaging from low-dose scans on different scanners and tracers. Methods Brain [18F]FDG PET imaging of 237 patients scanned with one scanner was used for the development of AI technology. The developed algorithm was then tested on [18F]FDG PET images of 45 patients scanned with three different scanners, [18F]FET PET images of 18 patients scanned with two different scanners, as well as [18F]Florbetapir images of 10 patients. A conditional generative adversarial network (GAN) was customized for cross-scanner and cross-tracer optimization. Three nuclear medicine physicians independently assessed the utility of the results in a clinical setting. Results The improvement achieved by AI recovery significantly correlated with the baseline image quality indicated by structural similarity index measurement (SSIM) (r = −0.71, p < 0.05) and normalized dose acquisition (r = −0.60, p < 0.05). Our cross-scanner and cross-tracer AI methodology showed utility based on both physical and clinical image assessment (p < 0.05). Conclusion The deep learning development for extensible application on unknown scanners and tracers may improve the trustworthiness and clinical acceptability of AI-based dose reduction.

PSMA PET/CT is routinely used for the detection of prostate cancer (PC). However, increased PSMA-ligand uptake has been described in a variety of benign and malignant tissues. A 71-year-old man with biochemical recurrence of PC initially treated with radical prostatectomy was referred for PSMA-ligand PET/CT. Apart from 1 lymph node with intense PSMA-ligand uptake, suspicious for metastasis, disseminated PSMA-ligand-avid subcutaneous lesions were seen. Histopathology of 1 of these lesions revealed an epidermoid cyst. Physicians should remain cognizant of non-PC-related causes of increased PSMA-ligand uptake, of which this case represent yet another example.

Purpose To establish the feasibility of shorter acquisition times (and by analogy, applied activity) on tumour detection and lesion contrast in digital PET/CT. Methods Twenty-one randomly selected patients who underwent oncological [18F]-FDG PET/CT on a digital PET/CT were retrospectively evaluated. Scan data were anonymously obtained and reconstructed in list-mode acquisition for a standard 2 min/bed position (bp), 1 min/bp and 30 s/bp (100%, 50% and 25% time or applied activity, respectively). Scans were randomized and read by two nuclear medicine physicians in a consensus read. Readers were blind to clinical details. Scans were evaluated for the number of pathological lesions detected. Measured uptake for lesions was evaluated by maximum and mean standardized uptake value (SUVmax and SUVmean, respectively) and tumour-to-backround ratio (TBR) were compared. Agreement between the three acquisitions was compared by Krippendorf’s alpha. Results Overall n = 100 lesions were identified in the 2 min and 1 min/bp acquisitions and n = 98 lesions in the 30 s/bp acquisitions. Agreement between the three acquisitions with respect to lesion number and tumour-to-background ratio showed almost perfect agreement (K’s α = 0.999). SUVmax, SUVmean and TBR likewise showed > 98% agreement, with longer acquisitions being associated with slightly higher mean TBR (2 min/bp 7.94 ± 4.41 versus 30 s/bp 7.84 ± 4.22, p Conclusion Shorter acquisition times have traditionally been associated with reduced lesion detectability or the requirement for larger amounts of radiotracer activity. These data confirm that this is not the case for new-generation digital PET scanners, where the known higher sensitivity results in clinically adequate images for shorter acquisitions. Only a small variation in the semi-quantitative parameters SUVmax, SUVmean and TBR was seen, confirming that either reduction of acquisition time or (by analogy) applied activity can be reduced as much as 75% in digital PET/CT without apparent clinical detriment.

OBJECTIVE To investigate the influence of colour scales on the interpretation of [68Ga]Ga-PSMA-11 PET/CT for the diagnosis of recurrent prostate cancer. METHODS 50 consecutive patients who underwent [68Ga]Ga-PSMA-11 PET/CT for recurrent prostate cancer were selected for this retrospective study. The scans were randomised, anonymised and read by five different readers first in the visually nonlinear colour scale 'PET-rainbow'. Scans were then rerandomised and read in the visually linear colour scale 'hot-metal new'. For each scan in each colour scale the numbers of pathological, equivocal and benign lesions were noted. Scans where the majority of readers (���3) reported at least one PET-positive lesion were recorded as 'pathological'. Patient-level sensitivity was obtained by composite standard with 14.8��������1.2���months of follow-up. RESULTS Increased numbers of lesions per patient were reported for all readers in PET-rainbow compared to hot-metal new (37.4��������15.2 vs. 33.9��������16.4, respectively, P���=���0.0005). On a per-patient basis, 43 scans were rated pathological in PET-rainbow, compared to 39 in hot-metal new. Follow-up was available for 30 patients confirming 26 pathological scans with positive follow-up in PET-rainbow, and 23 in hot-metal new. Three pathological scans were missed in hot-metal new. Patient-level sensitivity was higher for PET-rainbow (0.96) compared to hot-metal new (0.85). Inter-reader reliability was higher for hot-metal new (Fleiss �����=���0.76) compared to PET-rainbow (Fleiss �����=���0.60). CONCLUSION Use of PET-rainbow was associated with improved lesion detection and sensitivity compared to hot-metal new, although at cost of reduced inter-rater agreement. Consequently, the use of PET-rainbow for clinical routine and future studies involving [68Ga]Ga-PSMA-11 is recommended.

Purpose To investigate the performance of the new long axial field-of-view (LAFOV) Biograph Vision Quadra PET/CT and a standard axial field-of-view (SAFOV) Biograph Vision 600 PET/CT (both: Siemens Healthineers) system using an intra-patient comparison. Methods Forty-four patients undergoing routine oncological PET/CT were prospectively included and underwent a same-day dual-scanning protocol following a single administration of either 18F-FDG (n = 20), 18F-PSMA-1007 (n = 16) or 68Ga-DOTA-TOC (n = 8). Half the patients first received a clinically routine examination on the SAFOV (FOVaxial 26.3 cm) in continuous bed motion and then immediately afterwards on the LAFOV system (10-min acquisition in list mode, FOVaxial 106 cm); the second half underwent scanning in the reverse order. Comparisons between the LAFOV at different emulated scan times (by rebinning list mode data) and the SAFOV were made for target lesion integral activity, signal to noise (SNR), target lesion to background ratio (TBR) and visual image quality. Results Equivalent target lesion integral activity to the SAFOV acquisitions (16-min duration for a 106 cm FOV) were obtained on the LAFOV in 1.63 ± 0.19 min (mean ± standard error). Equivalent SNR was obtained by 1.82 ± 1.00 min LAFOV acquisitions. No statistically significant differences (p > 0.05) in TBR were observed even for 0.5 min LAFOV examinations. Subjective image quality rated by two physicians confirmed the 10 min LAFOV to be of the highest quality, with equivalence between the LAFOV and the SAFOV at 1.8 ± 0.85 min. By analogy, if the LAFOV scans were maintained at 10 min, proportional reductions in applied radiopharmaceutical could obtain equivalent lesion integral activity for activities under 40 MBq and equivalent doses for the PET component of Conclusion Improved image quality, lesion quantification and SNR resulting from higher sensitivity were demonstrated for an LAFOV system in a head-to-head comparison under clinical conditions. The LAFOV system could deliver images of comparable quality and lesion quantification in under 2 min, compared to routine SAFOV acquisition (16 min for equivalent FOV coverage). Alternatively, the LAFOV system could allow for low-dose examination protocols. Shorter LAFOV acquisitions (0.5 min), while of lower visual quality and SNR, were of adequate quality with respect to target lesion identification, suggesting that ultra-fast or low-dose acquisitions can be acceptable in selected settings.

Contains fulltext : 235569.pdf (Publisher’s version ) (Open Access) Medical imaging methods are assuming a greater role in the workup of patients with COVID-19, mainly in relation to the primary manifestation of pulmonary disease and the tissue distribution of the angiotensin-converting-enzyme 2 (ACE 2) receptor. However, the field is so new that no consensus view has emerged guiding clinical decisions to employ imaging procedures such as radiography, computer tomography (CT), positron emission tomography (PET), and magnetic resonance imaging, and in what measure the risk of exposure of staff to possible infection could be justified by the knowledge gained. The insensitivity of current RT-PCR methods for positive diagnosis is part of the rationale for resorting to imaging procedures. While CT is more sensitive than genetic testing in hospitalized patients, positive findings of ground glass opacities depend on the disease stage. There is sparse reporting on PET/CT with [(18)F]-FDG in COVID-19, but available results are congruent with the earlier literature on viral pneumonias. There is a high incidence of cerebral findings in COVID-19, and likewise evidence of gastrointestinal involvement. Artificial intelligence, notably machine learning is emerging as an effective method for diagnostic image analysis, with performance in the discriminative diagnosis of diagnosis of COVID-19 pneumonia comparable to that of human practitioners.

Purpose Amongst others, [68Ga]Ga-PSMA-11 and [18F]PSMA-1007 are available for the detection of recurrent prostate cancer (rPC). There are currently limited data comparing the performance of these two radioligands with respect to clinical outcomes or their cost efficacy, which this study aims to address. Methods Two hundred and forty-four patients undergoing PSMA PET/CT for rPC were retrospectively analysed for this study (one hundred and twenty two with each radiopharmaceutical) to generate rates of PET positivity, negativity and unclear findings. Patients underwent follow-up to determine the rate of additional examinations and to confirm PET findings. A Markov chain decision analysis was implemented to model clinical decision-making processes and to analyse clinical performance of the two tracers. We determine their clinical cost efficacies using cost data from several countries where both radiotracers are in routine use. Results The PET positivity rate was non-significantly higher for [18F]PSMA-1007 compared to [68Ga]Ga-PSMA-11 (91.8% vs. 86.9%, p = 0.68), whereas the rate of uncertain findings was significantly greater (17.2% vs. 8.25%, p = 0.02). The probability of a true positive finding was higher for [68Ga]Ga-PSMA-11 (0.90, 95% CI 0.70-0.98) vs. [18F]PSMA-1007 (0.81, 95% CI 0.66–0.91). A significantly (p < 0.0001) higher PPV for [68Ga]Ga-PSMA-11 (0.99, 95% CI 0.99–1.0 vs. 0.86) was found compared to [18F]PSMA-1007 (0.86, 95% CI 0.82–1.00). Intervention efficacy analysis favoured [68Ga]Ga-PSMA-11, where the number needed to image (to achieve a true positive finding) was 10.58 and the number needed to image to harm (to achieve a false positive finding) was − 8.08. A cost efficacy analysis favours [68Ga]Ga-PSMA-11 in three of the four jurisdictions analysed where health economic data was available (Switzerland, Israel, Australia) and [18F]PSMA-1007 in one jurisdiction (Denmark). Conclusion The analysis reveals a non-significantly higher PET positivity rate for [18F]PSMA-1007, but finds significantly greater rates of uncertain findings and false positive findings when compared to [68Ga]Ga-PSMA-11. We find differences in the two tracers in terms of clinical performance and cost efficacy. The method presented herein is generalisable and can be used with clinical or cost data for other countries or tracers.

The integrity of myelination is crucial for maintaining brain interstitial fluid (ISF) drainage in adults; however, the mechanism of ISF drainage with immature myelin in the developing brain remains unknown. In the present study, the ISF drainage from the caudate nucleus (Cn) to the ipsilateral cortex was studied at different developmental stages of the rat brain (P 10, 20, 30, 40, 60, 80, 10-80). The results show that the traced ISF drained to the cortex from Cn and to the thalamus in an opposite direction before P30. From P40, we found impeded drainage to the thalamus due to myelin maturation. This altered drainage was accompanied by enhanced cognitive and social functions, which were consistent with those in the adult rats. A significant difference in diffusion parameters was also demonstrated between the extracellular space (ECS) before and after P30. The present study revealed the alteration of ISF drainage regulated by myelin at different stages during development, indicating that a regional ISF homeostasis may be essential for mature psychological and cognitive functions.

Background Gastrin Releasing Peptide receptor (GRPr)-based radioligands have shown great promise for diagnostic imaging of GRPr-positive cancers, such as prostate and breast. The present study aims at developing and evaluating a versatile GRPr-based probe for both PET/SPECT imaging as well as intraoperative and therapeutic applications. The influence of the versatile chelator AAZTA5 on the radiometal labelling properties and the in vitro performance of the generated radiotracers were thoroughly investigated. The GRPr-based antagonist D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 was functionalized with the chelator 6-[Bis (carboxymethyl)amino]-1,4-bis (carboyxmethyl)-6-methyl-1,4-diazepane (AAZTA5) through the spacer 4-amino-1-carboxymethyl-piperidine (Pip) to obtain AAZTA5-Pip-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 (LF1). LF1 was radiolabelled with gallium-68 (PET), indium-111 (SPECT, intraoperative applications) and lutetium-177 (therapy, SPECT). In vitro evaluation included stability studies, determination of lipophilicity, protein-binding studies, determination of Kd and Bmax as well as internalization studies using the epithelial human prostate cancer cell line PC3. In vitro monotherapy as well as combination therapy studies were further performed to assess its applicability as a theranostic compound. Results LF1 was labelled with gallium-68, indium-111 and lutetium-177 within 5 min at room temperature (RT). The apparent molar activities (Am) were ranging between 50 and 60 GBq/μmol for the 68Ga-labelled LF1, 10–20 GBq/μmol for the 111In- and 177Lu-labelled LF1. The radiotracers were stable for a period of 4 h post labeling exhibiting a hydrophilic profile with an average of a LogDoctanol/PBS of − 3, while the bound activity to the human serum protein was approximately 10%. 68/natGa-LF1, 177/natLu-LF1 and 111/natIn-LF1 exhibited high affinity for the PC3 cells, with Kd values of 16.3 ± 2.4 nM, 10.3 ± 2.73 nM and 5.2 ± 1.9 nM, respectively, and the required concentration of the radiotracers to saturate the receptors (Bmax) was between 0.5 and 0.8 nM which corresponds to approximately 4 × 105 receptors per cell. Low specific internalization rate was found in cell culture, while the total specific cell surface bound uptake always exceeded the internalized activity. In vitro therapy studies showed that inhibition of PC3 cells growth is somewhat more efficient when combination of 177Lu-labelled LF1 with rapamycin is applied compared to 177Lu-laballed LF1 alone. Conclusion Encouraged by these promising in vitro data, preclinical evaluation of the LF1 precursor are planned in tumour models in vivo.

The aim of the present study is to evaluate the intra- and inter-observer agreement in assessing the renal function by means of 99mTc-MAG3 diuretic renography. One hundred and twenty adults were enrolled in the study. One experienced and one junior radiographer processed the renograms twice by assigning manual and semi-automated regions of interest. The differential renal function (DRF, %), time to maximum counts for the right and left kidney (TmaxR-TmaxL, min) and time to half-peak counts (T1/2, min) were calculated. The Bland–Altman analysis (bias±95% limits of agreement), Lin’s concordance correlation coefficient and weighted Fleiss’ kappa coefficient were used to assess agreement. Based on the Bland–Altman analysis, the intra-observer repeatability results for the experienced radiographer using the manual and the semi-automated techniques were 0.2 ± 2.6% and 0.3 ± 6.4% (DRF), respectively, −0.01 ± 0.24 and 0.00 ± 0.34 (TmaxR), respectively, and 0.00 ± 0.26 and 0.00 ± 0.33 (TmaxL), respectively. For the junior radiographer, the respective results were 0.5 ± 5.0% and 0.8 ± 9.4% (DRF), 0.00 ± 0.44 and 0.01 ± 0.28 (TmaxR), and 0.01 ± 0.28 and −0.02 ± 0.44 (TmaxL). The inter-observer repeatability for the manual method was 0.6 ± 5.0% (DRF), −0.10 ± 0.42 (TmaxR) and −0.05 ± 0.38 (TmaxL), and for the semi-automated method −0.2 ± 9.1% (DRF), 0.00 ± 0.31 (TmaxR) and −0.05 ± 0.40 (TmaxL). The weighted Fleiss’ kappa coefficient for the T1/2 assessments ranged between 0.85–0.97 for both intra- and inter-observer repeatability with both methods. These findings suggest a very good repeatability in DRF assessment with the manual method—especially for the experienced observer—but a less good repeatability with the semi-automated approach. The calculation of Tmax was also operator-dependent. We conclude that reader experience is important in the calculation of renal parameters. We therefore encourage reader training in renal scintigraphy. Moreover, the manual tool seems to perform better than the semi-automated tool. Thus, we encourage cautious use of automated tools and adjunct validation by manual methods where possible.

Molecular imaging of tauopathies is complicated by the differing specificities and off-target binding properties of available radioligands for positron emission tomography (PET). [18F]-APN-1607 ([18F]-PM-PBB3) is a newly developed PET tracer with promising properties for tau imaging. We aimed to characterize the cerebral binding of [18F]-APN-1607 in Alzheimer’s disease (AD) patients compared to normal control (NC) subjects. Therefore, we obtained static late frame PET recordings with [18F]-APN-1607 and [18F]-FDG in patients with a clinical diagnosis of AD group, along with an age-matched NC group ([18F]-APN-1607 only). Using statistical parametric mapping (SPM) and volume of interest (VOI) analyses of the reference region normalized standardized uptake value ratio maps, we then tested for group differences and relationships between both PET biomarkers, as well as their associations with clinical general cognition. In the AD group, [18F]-APN-1607 binding was elevated in widespread cortical regions (P < 0.001 for VOI analysis, familywise error-corrected P < 0.01 for SPM analysis). The regional uptake in AD patients correlated negatively with Mini-Mental State Examination score (frontal lobe: R = -0.632, P = 0.004; temporal lobe: R = -0.593, P = 0.008; parietal lobe: R = -0.552, P = 0.014; insula: R = -0.650, P = 0.003; cingulum: R = -0.665, P = 0.002) except occipital lobe (R = -0.417, P = 0.076). The hypometabolism to [18F]-FDG PET in AD patients also showed negative correlations with regional [18F]-APN-1607 binding in some signature areas of AD (temporal lobe: R = -0.530, P = 0.020; parietal lobe: R = -0.637, P = 0.003; occipital lobe: R = -0.567, P = 0.011). In conclusion, our results suggested that [18F]-APN-1607 PET sensitively detected tau deposition in AD and that individual tauopathy correlated with impaired cerebral glucose metabolism and cognitive function.

Highlights • Imaging biomarkers of the metabolic trajectory from HC, iRBD and PD are identified. • Frontal, limbic and occipital brain regions as imaging biomarkers in PD. • Frontal, limbic and occipital brain regions as imaging biomarkers of the phenoconversion from iRBD to PD., Objective Idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) is a prodromal stage of synucleinopathies such as Parkinson’s disease (PD). Positron emission tomography (PET) with 18F-FDG reveals metabolic perturbations, which are scored by spatial covariance analysis. However, the resultant pattern scores do not capture the spatially heterogeneous trajectories of metabolic changes between individual brain regions. Assuming metabolic progression occurs as a continuum from the healthy control (HC) condition to iRBD and then PD, we investigated spatial dynamics of progressively perturbed glucose metabolism in a cross-sectional study. Methods 19 iRBD patients, 38 PD patients and 19 HC subjects underwent 18F-FDG PET. The images were spatially normalized, scaled to the global mean uptake, and automatically parcellated. We contrasted regional metabolism by group, and allocated the inferred progression to one of several possible trajectories. We further investigated the correlations between 18F-FDG uptake and the disease duration in the iRBD and PD groups, respectively. We also explored relationships between 18F-FDG uptake and the Unified Parkinson’s Disease Rating Scale motor (UPDRS III) scores in the PD group. Results PD patients exhibited more extensive relative hyper- and hypo-metabolism than iRBD patients. We identified three dynamic metabolic trajectories, cross-sectional hypo- or hypermetabolism, cross-sectionally unchanged hypo- or hypermetabolism, cross-sectionally late hypo- or hypermetabolism, appearing only in the contrast of PD with iRBD. No correlation was found between relative 18F-FDG metabolism and disease duration in the iRBD group. Regional hyper- and hypo-metabolism in the PD patients correlated with disease duration or clinical UPDRS III scores. Conclusion Cerebral metabolism changes heterogeneously in a continuum extending from HC to iRBD and PD groups in this preliminary study. The distinctive metabolic trajectories point towards a potential neuroimaging biomarker for conversion of iRBD to frank PD, which should be amenable to advanced pattern recognition analysis in future longitudinal studies.

Purpose: 68Ga-PSMA-11 PET/CT is commonly performed at 1 h post injection (p.i.). However, various publications have demonstrated that most prostate cancer (PC) lesions exhibit higher contrast at later imaging. The aim of this study was to compare the “common” protocol of 68Ga-PSMA-11 PET/CT with a modified protocol. Methods: In 2017, we used the following scanning protocol for 68Ga-PSMA-11 PET/CT in patients with recurrent PC: acquisition at 1 h p.i. without further preparations. From 2018, all scans were conducted at 1.5 h p.i. In addition, patients were orally hydrated with 1 L of water 0.5 h p.i. and were injected with 20 mg of furosemide 1 h p.i. Both protocols including 112 patients (2017) and 156 (modified protocol in 2018) were retrospectively compared. Rates of pathologic scans, maximum standardized uptake values (SUVmax), and tumor contrast (ratio lesion-SUVmax/background-SUVmean) as well as average standardized uptake values (SUVmean) of urinary bladder were analyzed. Results: Both tumor contrast and tracer uptake were significantly (p < 0.001) higher in the novel protocol. Although statistically not significant, the rates of pathologic scans were also higher in the modified protocol: 76.3% vs. 68.8% for all PSA values including 38.9% vs. 25.0% for PSA < 0.5 ng/ml and 60.0% vs. 56.7% for PSA > 0.5–≤ 2.0 ng/ml. Average SUVmean of the urinary bladder was significantly (p < 0.001) lower with the modified protocol. Conclusions: The modified protocol, which includes a combination of delayed image acquisition at 1.5 h p.i., hydration, and furosemide resulted in higher tumor contrast and seems to have the potential to increase the rates of pathological scans, especially at low PSA levels.

PURPOSE Differentiating between prostate cancer (PC) lesions and benign structures which exhibit radiotracer uptake in PSMA-ligand PET/CT can be challenging. Additional late imaging has been shown to be a powerful method for the discrimination between PC and non-PC lesions, owing to the increasing tracer uptake of the former. Nevertheless, there are no pre-existing studies which describe the dynamic tracer uptake for ganglia, which this present study aims to address. METHODS Fifty consecutive patients with PC who received standard and late 68Ga-PSMA-11-PET/CT (by local protocol at 1.5 h "standard" and 2.5 h p.i. "late") underwent retrospective evaluation. All lesions with a tracer uptake above local background indicative for ganglia as well as PC lesions were analysed with regard to their maximum standardised uptake values (SUVmax) and localisation. RESULTS Overall, 86 PSMA-positive ganglia were identified in 70% (n = 35) of the patients. Five ganglia exhibited PSMA avidity at late imaging only, and three at standard imaging only. A total of 66 lesions suggestive for PC were detected in 44 patients (88%), of which 45% (n = 30) were morphologically identified as lymph nodes (LN), the remainder being locally recurrent lesions or bone metastases. No solid organ metastases were present in our cohort. At late scanning, 73% of the LN exhibited an increase in SUVmax, whereas 65% of the ganglia exhibited a decreasing or stable SUVmax. CONCLUSION Whereas the presence of increasing tracer uptake in potential PC lesions can provide additional data about the likelihood of malignancy, increasing SUVmax alone does not reliably differentiate between ganglia and PC lesions and is a potential diagnostic pitfall. We therefore recommend high-resolution CT to enable morphological characterisation of ganglia.

The drainage of brain interstitial fluid (ISF) has been observed to slow down following neuronal excitation, although the mechanism underlying this phenomenon is yet to be elucidated. In searching for the changes in the brain extracellular space (ECS) induced by electrical pain stimuli in the rat thalamus, significantly decreased effective diffusion coefficient (DECS) and volume fraction (α) of the brain ECS were shown, accompanied by the slowdown of ISF drainage. The morphological basis for structural changes in the brain ECS was local spatial deformation of astrocyte foot processes following neuronal excitation. We further studied aquaporin-4 gene (APQ4) knockout rats in which the changes of the brain ECS structure were reversed and found that the slowed DECS and ISF drainage persisted, confirming that the down-regulation of ISF drainage following neuronal excitation was mainly attributable to the release of neurotransmitters rather than to structural changes of the brain ECS. Meanwhile, the dynamic changes in the DECS were synchronized with the release and elimination processes of neurotransmitters following neuronal excitation. In conclusion, the downregulation of ISF drainage following neuronal excitation was found to be caused by the restricted diffusion in the brain ECS, and DECS mapping may be used to track the neuronal activity in the deep brain.

BACKGROUND Amyloid-β (Aβ) accumulation in brain of patients with suspected Alzheimer's disease (AD) can be assessed by positron emission tomography (PET) in vivo. While visual classification prevails in the clinical routine, semiquantitative PET analyses may enable more reliable evaluation of cases with a visually uncertain, borderline Aβ accumulation. OBJECTIVE We evaluated different analysis approaches (visual/semiquantitative) to find the most accurate and sensitive interpretation of Aβ-PET for predicting risk of progression from mild cognitive impairment (MCI) to AD. METHODS Based on standard uptake value (SUV) ratios of a cortical-composite volume of interest of 18F-AV45-PET from MCI subjects (n = 396, ADNI database), we compared three different reference region (cerebellar grey matter, CBL; brainstem, BST; white matter, WM) normalizations and the visual read by receiver operator characteristics for calculating a hazard ratio (HR) for progression to Alzheimer's disease dementia (ADD). RESULTS During a mean follow-up time of 45.6±13.0 months, 28% of the MCI cases (110/396) converted to ADD. Among the tested methods, the WM reference showed best discriminatory power and progression-risk stratification (HRWM of 4.4 [2.6-7.6]), but the combined results of the visual and semiquantitative analysis with all three reference regions showed an even higher discriminatory power. CONCLUSION A multi-analytical composite of visual and semiquantitative reference tissue analyses of 18F-AV45-PET gave improved risk stratification for progression from MCI to ADD relative to performance of single read-outs. This optimized approach is of special interest for prospective treatment trials, which demand a high accuracy.

Purpose Positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) reveals altered cerebral metabolism in individuals with mild cognitive impairment (MCI) and Alzheimer’s dementia (AD). Previous metabolic connectome analyses derive from groups of patients but do not support the prediction of an individual’s risk of conversion from present MCI to AD. We now present an individual metabolic connectome method, namely the Kullback-Leibler Divergence Similarity Estimation (KLSE), to characterize brain-wide metabolic networks that predict an individual’s risk of conversion from MCI to AD. Methods FDG-PET data consisting of 50 healthy controls, 332 patients with stable MCI, 178 MCI patients progressing to AD, and 50 AD patients were recruited from ADNI database. Each individual’s metabolic brain network was ascertained using the KLSE method. We compared intra- and intergroup similarity and difference between the KLSE matrix and group-level matrix, and then evaluated the network stability and inter-individual variation of KLSE. The multivariate Cox proportional hazards model and Harrell’s concordance index (C-index) were employed to assess the prediction performance of KLSE and other clinical characteristics. Results The KLSE method captures more pathological connectivity in the parietal and temporal lobes relative to the typical group-level method, and yields detailed individual information, while possessing greater stability of network organization (within-group similarity coefficient, 0.789 for sMCI and 0.731 for pMCI). Metabolic connectome expression was a superior predictor of conversion than were other clinical assessments (hazard ratio (HR) = 3.55; 95% CI, 2.77–4.55; P Conclusion The KLSE indicator identifies abnormal brain networks predicting an individual’s risk of conversion from MCI to AD, thus potentially constituting a clinically applicable imaging biomarker.

To illustrate the [18F]FDG-PET/CT findings in patients affected by cancer with clinical diagnosis of Covid-19 METHODS: We retrospectively reviewed the cases of patients who showed pulmonary involvement unrelated to cancer metastases on March 13 and 16 2020. We reviewed the scans, collected medical history, and exposure information.Among the 13 scans, we identified 5 cases with imaging findings suspicious for viral infection. Peripheral lung consolidations and/or ground-glass opacities in two or more lobes were found. Lung abnormalities displayed increased [18F]FDG uptake (SUVmax 4.3-11.3). All the patients on the day of PET/CT acquisition were asymptomatic, and they did not have fever or cough. In view of the PET/CT findings, home isolation, symptom surveillance, and treatment (in 3/5 patients) were indicated. At 1-week follow-up, 2/5 patients experienced the onset of mild respiratory symptoms.The [18F]FDG-PET/CT can identify probable Covid-19 disease in the absence or before symptoms onset and can guide patient management. Nuclear medicine staff needs to be aware of the possibility of contact with patients affected by the SARS-CoV-2 infection even if they do not present any symptom. Therefore, safety measures need to be adopted for other patients and hospital staff in order to block the spread of infection.

A 76-year-old man with metastatic adenocarcinoma of the prostate presented with increasing dyspnea. After being treated initially with drainage and afterwards with pleurodesis, he was referred for Ga-prostate-specific membrane antigen 11 PET/CT imaging for restaging purposes. PET/CT demonstrated extensive Ga-prostate-specific membrane antigen 11 uptake in the right pleura. Histopathology confirmed the rare case of malignant pleural effusion from metastatic prostate cancer.

A patient with bone metastases of prostate cancer was referred for 68Ga-PSMA-11 PET/CT. Compared to a 68Ga-PSMA-11 PET/CT four months previously, the CT-component of the current PET/CT showed morphological progress in all lesions despite continuous therapy with docetaxel and denosumab. Contrarily, the PET-component showed a reduction of tracer-uptake, which correlated with PSA decrease between the two PET/CT-scans (16.2 ng/ml vs. 3.1 ng/ml). This case highlights 68Ga-PSMA-11 PET/CT as a promising tool for therapy monitoring of prostate cancer and could serve as a basis for a novel monitoring strategy. Volume progress shown by CT must not be classified as tumor progress, but as bone remodeling following effective therapy.

Owing to their superior uptake and higher detection rate, PSMA-labelled radioligands have largely replaced choline in routine clinical imaging of recurrent prostate cancer (PCa). Nevertheless, even at high PSA values, a small number of patients can present with PSMA negative prostate cancer (PC) lesions. For such patients choline PET continues to play an important role.