Purpose
This study proposes an automated prostate cancer (PC) lesion characterization method based on the deep neural network to determine tumor burden on
68
Ga-PSMA-11 PET/CT to potentially ...facilitate the optimization of PSMA-directed radionuclide therapy.
Methods
We collected
68
Ga-PSMA-11 PET/CT images from 193 patients with metastatic PC at three medical centers. For proof-of-concept, we focused on the detection of pelvis bone and lymph node lesions. A deep neural network (triple-combining 2.5D U-Net) was developed for the automated characterization of these lesions. The proposed method simultaneously extracts features from axial, coronal, and sagittal planes, which mimics the workflow of physicians and reduces computational and memory requirements.
Results
Among all the labeled lesions, the network achieved 99% precision, 99% recall, and an F1 score of 99% on bone lesion detection and 94%, precision 89% recall, and an F1 score of 92% on lymph node lesion detection. The segmentation accuracy is lower than the detection. The performance of the network was correlated with the amount of training data.
Conclusion
We developed a deep neural network to characterize automatically the PC lesions on
68
Ga-PSMA-11 PET/CT. The preliminary test within the pelvic area confirms the potential of deep learning methods. Increasing the amount of training data should further enhance the performance of the proposed method and may ultimately allow whole-body assessments.
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
18
FPSMA-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
18
FPSMA-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
18
FPSMA-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
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
18
F-FDG (
n
= 20),
18
F-PSMA-1007 (
n
= 16) or
68
Ga-DOTA-TOC (
n
= 8). Half the patients first received a clinically routine examination on the SAFOV (FOV
axial
26.3 cm) in continuous bed motion and then immediately afterwards on the LAFOV system (10-min acquisition in list mode, FOV
axial
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 <1 mSv.
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.
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
18
F-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
< 0.05).
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.
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 (
68
Ga-PSMA-11,
18
F-PSMA-1007,
18
F-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
68
GaGa-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
68
GaGa-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
68
GaGa 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.
Coding variants in the triggering receptor expressed on myeloid cells 2 (TREM2) are associated with late-onset Alzheimer's disease (AD). We demonstrate that amyloid plaque seeding is increased in the ...absence of functional Trem2. Increased seeding is accompanied by decreased microglial clustering around newly seeded plaques and reduced plaque-associated apolipoprotein E (ApoE). Reduced ApoE deposition in plaques is also observed in brains of AD patients carrying TREM2 coding variants. Proteomic analyses and microglia depletion experiments revealed microglia as one origin of plaque-associated ApoE. Longitudinal amyloid small animal positron emission tomography demonstrates accelerated amyloidogenesis in Trem2 loss-of-function mutants at early stages, which progressed at a lower rate with aging. These findings suggest that in the absence of functional Trem2, early amyloidogenesis is accelerated due to reduced phagocytic clearance of amyloid seeds despite reduced plaque-associated ApoE.
Purpose
Positron emission tomography (PET) with
18
F-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
< 0.001). The predictive performance improved further upon combining clinical variables in the Cox model, i.e., C-indices 0.728 (clinical), 0.730 (group-level pattern model), 0.750 (imaging connectome), and 0.794 (the combined model).
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.
Amyloid positron-emission-tomography (PET) offers an important research and diagnostic tool for investigating Alzheimer's disease (AD). The majority of amyloid PET studies have used the cerebellum as ...a reference region, and clinical studies have not accounted for atrophy-based partial volume effects (PVE). Longitudinal studies using cerebellum as reference tissue have revealed only small mean increases and high inter-subject variability in amyloid binding. We aimed to test the effects of different reference regions and PVE-correction (PVEC) on the discriminatory power and longitudinal performance of amyloid PET.
We analyzed 18F-AV45 PET and T1-weighted MRI data of 962 subjects at baseline and two-year follow-up data of 258 subjects. Cortical composite volume-of-interest (VOI) values (COMP) for tracer uptake were generated using either full brain atlas VOIs, gray matter segmented VOIs or gray matter segmented VOIs after VOI-based PVEC. Standard-uptake-value ratios (SUVR) were calculated by scaling the COMP values to uptake in cerebellum (SUVRCBL), brainstem (SUVRBST) or white matter (SUVRWM). Mean SUV, SUVR, and changes after PVEC were compared at baseline between diagnostic groups of healthy controls (HC; N=316), mild cognitive impairment (MCI; N=483) and AD (N=163). Receiver operating characteristics (ROC) were calculated for the discriminations between HC, MCI and AD, and expressed as area under the curve (AUC). Finally, the longitudinal 18F-AV45-PET data were used to analyze the impact of quantitation procedures on apparent changes in amyloid load over time.
Reference region SUV was most constant between diagnosis groups for the white matter. PVEC led to decreases of COMP-SUV in HC (−18%) and MCI (−10%), but increases in AD (+7%). Highest AUCs were found when using PVEC with white matter scaling for the contrast between HC/AD (0.907) or with brainstem scaling for the contrast between HC/MCI (0.658). Longitudinal increases were greatest in all diagnosis groups with application of PVEC, and inter-subject variability was lowest for the white matter reference.
Thus, discriminatory power of 18F-AV45-PET was improved by use of a VOI-based PVEC and white matter or brainstem rather than cerebellum reference region. Detection of longitudinal amyloid increases was optimized with PVEC and white matter reference tissue.
•Different reference regions were compared for 18F-AV45 PET quantification.•Effects of segmentation and partial volume effect correction (PVEC) were assessed.•White matter (WM) SUV was most stable between diagnosis groups.•WM and brainstem reference improved discriminatory power compared to cerebellum.•WM reference including PVEC distinctly improved longitudinal PET assessment.
Purpose
While acquisition of images in
68
GaGa-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
GaGa-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
< 0.001) and SNR was improved with borderline significance (4 h: 33.02 vs 1 h: 24.80,
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
GaGa-PSMA-11 may be preferable when performed on LAFOV systems.
PDF
![Improved longitudinal [18F]...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/1053-8119_1095-9572/small "Improved longitudinal [18F]-AV45 amyloid PET by white matter reference and VOI-based partial volume effect correction")