Freely Available, Fully Automated AI-Based Analysis of Primary Tumour and Metastases of Prostate Cancer in Whole-Body [F-18]-PSMA-1007 PET-CT

Here, we aimed to develop and validate a fully automated artificial intelligence (AI)-based method for the detection and quantification of suspected prostate tumour/local recurrence, lymph node metastases, and bone metastases from [F-18]PSMA-1007 positron emission tomography-computed tomography (PET-CT) images. Images from 660 patients were included. Segmentations by one expert reader were ground truth. A convolutional neural network (CNN) was developed and trained on a training set, and the performance was tested on a separate test set of 120 patients. The AI method was compared with manual segmentations performed by several nuclear medicine physicians. Assessment of tumour burden (total lesion volume (TLV) and total lesion uptake (TLU)) was performed. The sensitivity of the AI method was, on average, 79% for detecting prostate tumour/recurrence, 79% for lymph node metastases, and 62% for bone metastases. On average, nuclear medicine physicians\u27 corresponding sensitivities were 78%, 78%, and 59%, respectively. The correlations of TLV and TLU between AI and nuclear medicine physicians were all statistically significant and ranged from R = 0.53 to R = 0.83. In conclusion, the development of an AI-based method for prostate cancer detection with sensitivity on par with nuclear medicine physicians was possible. The developed AI tool is freely available for researchers

[18F]PSMA-1007 renal uptake parameters: Reproducibility and relationship to estimated glomerular filtration rate

BackgroundScintigraphy with technetium-99m-labelled dimercaptosuccinic acid ([99mTc]Tc-DMSA) is widely used for renal cortical imaging. Uptake of [99mTc]Tc-DMSA has been shown to correlate with glomerular filtration rate (GFR). Prostate-specific membrane antigen (PSMA) radiopharmaceuticals used for positron emission tomography (PET) show high renal uptake and are being investigated for renal imaging. [68Ga]Ga-PSMA-11 PET parameters have been shown to correlate with estimated GFR (eGFR). The aim of this study was to investigate the relationship between renal [18F]PSMA-1007 uptake and eGFR.MethodsHundred and eighty-five patients underwent PET imaging at 1 and 2 h after injection of 4.0 ± 0.2 MBq [18F]PSMA-1007. Serum creatinine levels were measured and GFR estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) equations. Fifteen patients were excluded due to missing or incorrect data. Thus, data from 170 patients were analyzed. Kidneys were segmented in the PET images using a convolutional neural network with manual correction. For each kidney, mean standardized uptake value (SUVmean) and segmentation volume in millilitres were measured. Linear regression analyses were performed with eGFR as the outcome variable.ResultsVariation in the eGFR values was explained to a significant degree by SUVmean and renal segmentation volume in both the 1 and 2 h images. This correlation was stronger for CKD-EPI eGFR (1 h R2 = 0.64; 2 h R2 = 0.64) than for MDRD eGFR (1 h R2 = 0.47; 2 h R2 = 0.45).ConclusionRenal [18F]PSMA-1007 uptake parameters correlate with eGFR and are indicative of renal cortical function

Dose-reduced [18F]PSMA-1007 PET is feasible for functional imaging of the renal cortex

BackgroundIn Prostate-specific membrane antigen (PSMA) positron emission tomography with computed tomography (PET-CT), there is significant renal uptake. The standard in renal cortical functional imaging is scintigraphy with technetium-99m labeled dimercaptosuccinic acid (DMSA). Using [68Ga]Ga-PSMA-11 PET for renal imaging has been suggested, but using [18F]PSMA-1007 has not been explored. The aims of this study were to establish the optimal time point for renal imaging after [18F]PSMA-1007 injection, to investigate the reproducibility of split renal uptake measurements, and to determine the margin for reduction in administered activity.MethodsTwelve adult male patients with prostate cancer underwent [18F]PSMA-1007 PET-CT at 8 time points up to 5.5 h post-injection (p.i.). List-mode data were binned to durations of 10 to 120 s per bed position (bp). Left renal percentage of total renal uptake (LRU%) was measured, and the difference between highest and lowest measurement per patient (“delta max”) was calculated. Images acquired at 1 h, 2 h, and 5.5 h p.i. with durations of 10 to 120 s/bp were rated regarding image quality.ResultsImaging at 2 h p.i. with 60 s/bp yielded acceptable quality in all cases. Increasing acquisition time to 15 min for a single bp would allow reducing administered activity to 0.27 MBq/kg, resulting in an effective dose of 0.4 mSv for a 1-year old child weighing 10 kg. The median delta max of LRU% measurements was 2.7% (range 1.8–7.3%).ConclusionsRenal [18F]PSMA-1007 PET-CT is feasible, with imaging 2 h p.i., acceptable split renal uptake variability, and effective dose and acquisition time comparable to those of [99mTc]Tc-DMSA scintigraphy

AI-based quantification of whole-body tumour burden on somatostatin receptor PET/CT

Abstract Background Segmenting the whole-body somatostatin receptor-expressing tumour volume (SRETVwb) on positron emission tomography/computed tomography (PET/CT) images is highly time-consuming but has shown value as an independent prognostic factor for survival. An automatic method to measure SRETVwb could improve disease status assessment and provide a tool for prognostication. This study aimed to develop an artificial intelligence (AI)-based method to detect and quantify SRETVwb and total lesion somatostatin receptor expression (TLSREwb) from [68Ga]Ga-DOTA-TOC/TATE PET/CT images. Methods A UNet3D convolutional neural network (CNN) was used to train an AI model with [68Ga]Ga-DOTA-TOC/TATE PET/CT images, where all tumours were manually segmented with a semi-automatic method. The training set consisted of 148 patients, of which 108 had PET-positive tumours. The test group consisted of 30 patients, of which 25 had PET-positive tumours. Two physicians segmented tumours in the test group for comparison with the AI model. Results There were good correlations between the segmented SRETVwb and TLSREwb by the AI model and the physicians, with Spearman rank correlation coefficients of r = 0.78 and r = 0.73, respectively, for SRETVwb and r = 0.83 and r = 0.81, respectively, for TLSREwb. The sensitivity on a lesion detection level was 80% and 79%, and the positive predictive value was 83% and 84% when comparing the AI model with the two physicians. Conclusion It was possible to develop an AI model to segment SRETVwb and TLSREwb with high performance. A fully automated method makes quantification of tumour burden achievable and has the potential to be more widely used when assessing PET/CT images

[18F]PSMA-1007 PET is comparable to [99mTc]Tc-DMSA SPECT for renal cortical imaging

Abstract Background Scintigraphy using technetium-99m labelled dimercaptosuccinic acid ([99mTc]Tc-DMSA), taken up in the proximal tubules, is the standard in functional imaging of the renal cortex. Recent guidelines recommend performing [99mTc]Tc-DMSA scintigraphy with single photon emission computed tomography (SPECT). Prostate-specific membrane antigen (PSMA) targeted positron emission tomography (PET) is used for staging and localization of recurrence in prostate cancer. A high renal uptake is often seen on PSMA PET, concordant with known PSMA expression in proximal tubules. This suggests PSMA PET could be used analogous to [99mTc]Tc-DMSA scintigraphy for renal cortical imaging. [18F]PSMA-1007 is a promising radiopharmaceutical for this purpose due to low urinary clearance. In this study, we aimed to compare [18F]PSMA-1007 PET to [99mTc]Tc-DMSA SPECT regarding split renal uptake and presence of renal uptake defects, in patients with prostate cancer. Three readers interpreted PET and SPECT images regarding presence of renal uptake defects, with each kidney split into cranial, mid and caudal segments. Kidneys were segmented in PET and SPECT images, and left renal uptake as a percentage of total renal uptake was measured. Results Twenty patients with prostate cancer were included. 2 participants had single kidneys; thus 38 kidneys were evaluated. A total of 29 defects were found on both [99mTc]Tc-DMSA SPECT and [18F]PSMA-1007 PET. Cohen’s kappa for concordance regarding presence of any defect was 0.76 on a per-segment basis and 0.67 on a per-kidney basis. Spearman’s r for left renal uptake percentage between [99mTc]Tc-DMSA SPECT and [18F]PSMA-1007 PET was 0.95. Conclusions [18F]PSMA-1007 PET is comparable to [99mTc]Tc-DMSA SPECT for detection of uptake defects in this setting. Measurements of split renal function made using [18F]PSMA-1007 PET are valid and strongly correlated to measurements made with [99mTc]Tc-DMSA SPECT

Effects of the sigma-1 receptor agonist 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)-piperazine dihydro-chloride on inflammation after stroke.

Activation of the sigma-1 receptor (Sig-1R) improves functional recovery in models of experimental stroke and is known to modulate microglia function. The present study was conducted to investigate if Sig-1R activation after experimental stroke affects mediators of the inflammatory response in the ischemic hemisphere. Male Wistar rats were subjected to transient occlusion of the middle cerebral artery (MCAO) and injected with the specific Sig-1R agonist 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine dihydrochloride (SA4503) or saline for 5 days starting on day 2 after MCAO. Treatment did not affect the increased levels of the pro-inflammatory cytokines interleukin 1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), interleukin 4 (IL-4), interleukin 5 (IL-5), and interleukin 13 (IL-13) in the infarct core and peri-infarct area after MCAO. In addition, treatment with SA4503 did not affect elevated levels of nitrite, TNF-α and IL-1β observed in primary cultures of microglia exposed to combined Hypoxia/Aglycemia, while the unspecific sigma receptor ligand 1,3-di-o-tolylguanidine (DTG) significantly decreased the production of nitrite and levels of TNF-α. Analysis of the ischemic hemisphere also revealed increased levels of ionized calcium binding adaptor molecule 1 (Iba1) levels in the infarct core of SA4503 treated animals. However, no difference in Iba1 immunoreactivity was detected in the infarct core. Also, levels of the proliferation marker proliferating cell nuclear antigen (PCNA) and OX-42 were not increased in the infarct core in rats treated with SA4503. Together, our results suggest that sigma-1 receptor activation affects Iba1 expression in microglia/macrophages of the ischemic hemisphere after experimental stroke but does not affect post-stroke inflammatory mediators

First clinical experience of a ring-configured cadmium zinc telluride camera : A comparative study versus conventional gamma camera systems

BACKGROUND: A novel semiconductor cadmium zinc telluride (CZT) gamma camera system using a block sequential regularized expectation maximization (BSREM) reconstruction algorithm is now clinically available. Here we investigate how a multi-purpose ring-configurated CZT system can be safely applied in clinics and describe the initial optimization process.METHOD: Seventy-six patients (bone-, cardiac- and lung scan) were scanned on a conventional gamma camera (planar and/or single-photon emission computed tomography [SPECT]/SPECT-CT) used in clinical routine and on the ring-configurated CZT camera Starguide (GE Healthcare). These data were used to validate and optimize the Starguide system for routine clinical use.RESULTS: Comparable image quality for the Starguide system, to that of the conventional gamma camera, was achieved for bone scan (4 min/bed position [BP] using a relative difference prior [RDP] with gamma 2 and beta 0.4, along with 10 iterations and 10 subsets), cardiac scan (8 min [stress] and 3 min 20 s [rest] using median root prior [MRP] with beta 0.07 non attenuation corrected and 0.008 attenuation corrected and 50 interations and 10 subsets for both stress and rest) and lung scan (10 min [vent] and 5 min [perf] using RDP with gamma 0.5 and beta 0.03 [vent] and 0.02 [perf] and 20 interations and 10 subsets for both vent and perf).CONCLUSIONS: It was possible to transition from a conventional gamma camera to the Starguide system as part of the clinical routine, with acceptable image quality. Images from the Starguide system were deemed to be at least as good as those from a conventional gamma camera

Analysis of cytokine in the ischemic hemipshere.

<p>Levels of intraparenchymal TNF-α, IFN-γ, IL-1β, IL-4, IL-5 and IL-13 of the ischemic core and peri-infarct region were measured from ischemic animals treated with saline (n = 8, white bars) or SA4503 (0.5 mg/kg, s.c., n = 8, gray bars) and of cortices from sham treated animals (saline n = 3; SA4503, 0.5 mg/kg s.c., n = 3) by multiplex ELISA using a SECTOR Imager 6000 reader. Data are presented as means ± sd. Statistical analysis was performed one-way ANOVA and posthoc Bonferroni correction (*<i>p</i><0.05 vs sham saline, **<i>p</i><0.05 vs ischemic core saline, #<i>p</i><0.05 vs sham SA4503, ##<i>p</i><0.05 vs ischemic core SA4503).</p

Iba1 levels in the infarct core after MCAO.

<p>(A) Western blot of samples from the infarct core and the peri-infarct area from SA4503 (0.5 mg/kg s.c.; n = 7) and vehicle treated rats (n = 6) and respective densitometric analyses (mean±SD, *p<0.05, t-test) at day 7 following MCAO. Note that each lane represents an individual animal. (B) Average Iba1 immunoreactivity in the ischemic hemisphere of vehicle and SA4503 rats on day 7 after tMCAo. Average Cy3 fluorescence intensity is presented per pixel (0 to 255) within the indicated areas considered as immunopositive Iba1, respectively (I/pixel; mean±s.d., n = 3 per treatment).</p

Effects of SA4503 and DTG on microglia after Hypoxia/Aglycemia.

<p>(<b>A</b>) Iba1 expressing microglia 24 h after normoxic control or combined H/A. Scale bar 10 µm. (<b>B</b>) Nitrite concentrations in the supernatant medium 24 h after stimulation as indicated in the figure. SA4503 (SA, 10 µM) and DTG (300 µM) were added to the culture medium immediately after H/A or normoxic control stimulation, respectively. Stimulation with lipopolysaccharide (LPS, 1 µg/mL) served as control. Abbreviations: ctrl – normoxic control, H/A – Hypoxia/Aglycemia. Data are presented as means ± SEM, *p<0.01 vs all control stimulations, #p<0.05 vs H/A DTG, one-way ANOVA and posthoc Bonferroni correction. <b>(C)</b> Levels of TNF-α and IL-1β after control or H/A stimulation and respective treatments (SA4503, 10 µM; DTG, 300 µM) for 24 hours. Data are presented as means ± SEM, n = 20 each experimental condition, *p<0.01 vs all control stimulations, #p<0.05 vs H/A DTG, one-way ANOVA and posthoc Bonferroni correction.</p