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

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.

The α-synuclein PET tracer [18F] ACI-12589 distinguishes multiple system atrophy from other neurodegenerative diseases.

A positron emission tomography (PET) tracer detecting α-synuclein pathology will improve the diagnosis, and ultimately the treatment of α-synuclein-related diseases. Here we show that the PET ligand, [18F]ACI-12589, displays good in vitro affinity and specificity for pathological α-synuclein in tissues from patients with different α-synuclein-related disorders including Parkinson's disease (PD) and Multiple-System Atrophy (MSA) using autoradiography and radiobinding techniques. In the initial clinical evaluation we include 23 participants with α-synuclein related disorders, 11 with other neurodegenerative disorders and eight controls. In vivo [18F]ACI-12589 demonstrates clear binding in the cerebellar white matter and middle cerebellar peduncles of MSA patients, regions known to be highly affected by α-synuclein pathology, but shows limited binding in PD. The binding statistically separates MSA patients from healthy controls and subjects with other neurodegenerative disorders, including other synucleinopathies. Our results indicate that α-synuclein pathology in MSA can be identified using [18F]ACI-12589 PET imaging, potentially improving the diagnostic work-up of MSA and allowing for detection of drug target engagement in vivo of novel α-synuclein targeting therapies.

Clinical Utility of Tau Positron Emission Tomography in the Diagnostic Workup of Patients With Cognitive Symptoms.

Importance: It is important to determine the added clinical value for tau positron emission tomography (PET) in the diagnostic workup of patients with cognitive symptoms before widespread implementation in clinical practice. Objective: To prospectively study the added clinical value of PET detecting tau pathology in Alzheimer disease (AD). Design, Setting, and Participants: This prospective cohort study (Swedish BioFINDER-2 study) took place from May 2017 through September 2021. A total of 878 patients with cognitive complaints were referred to secondary memory clinics in southern Sweden and then recruited to the study. In total, 1269 consecutive participants were approached, but 391 did not meet inclusion criteria or did not complete the study. Exposures: Participants underwent a baseline diagnostic workup, including clinical examination, medical history, cognitive testing, blood and cerebrospinal fluid sampling, magnetic resonance imaging of the brain, and a tau PET ([18F]RO948) scan. Main Outcomes and Measures: The primary end points were change in diagnosis and change in AD drug therapy or other drug treatment between the pre- and post-PET visits. A secondary end point was the change in diagnostic certainty between the pre- and post-PET visits. Results: A total of 878 participants with a mean age of 71.0 (SD, 8.5) years (491 male [56%]) were included. The tau PET result led to a change in diagnoses in 66 participants (7.5%) and a change in medication in 48 participants (5.5%). The study team found an association with overall increased diagnostic certainty after tau PET in the whole data set (from 6.9 [SD, 2.3] to 7.4 [SD, 2.4]; P < .001). The certainty was higher in participants with a pre-PET diagnosis of AD (from 7.6 [SD, 1.7] to 8.2 [SD, 2.0]; P < .001) and increased even further in participants with a tau PET positive result supporting an AD diagnosis (from 8.0 [SD, 1.4] to 9.0 [SD, 0.9]; P < .001). The association with tau PET results had the largest effect sizes in participants with pathological amyloid-ß (Aß) status, whereas no significant change in diagnoses was seen in participants with normal Aß status. Conclusions and Relevance: The study team reported a significant change in diagnoses and patient medication when tau PET was added to an already extensive diagnostic workup that included cerebrospinal fluid AD biomarkers. Including tau PET was associated with a significant increase in certainty of underlying etiology. The effect sizes for certainty of etiology and diagnosis were largest in the Aß-positive group and the study team suggests that clinical use of tau PET be limited to populations with biomarkers indicating Aß positivity.

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

BACKGROUND: Scintigraphy with technetium-99m-labelled dimercaptosuccinic acid ([99m Tc]Tc-DMSA) is widely used for renal cortical imaging. Uptake of [99m Tc]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. [68 Ga]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 [18 F]PSMA-1007 uptake and eGFR. METHODS: Hundred and eighty-five patients underwent PET imaging at 1 and 2 h after injection of 4.0 ± 0.2 MBq [18 F]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. RESULTS: Variation 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). CONCLUSION: Renal [18 F]PSMA-1007 uptake parameters correlate with eGFR and are indicative of renal cortical function.

[18F]RO948 tau positron emission tomography in genetic and sporadic frontotemporal dementia syndromes.

PURPOSE: To examine [18F]RO948 retention in FTD, sampling the underlying protein pathology heterogeneity. METHODS: A total of 61 individuals with FTD (n = 35), matched cases of AD (n = 13) and Aß-negative cognitively unimpaired individuals (n = 13) underwent [18F]RO948PET and MRI. FTD included 21 behavioral variant FTD (bvFTD) cases, 11 symptomatic C9orf72 mutation carriers, one patient with non-genetic bvFTD-ALS, one individual with bvFTD due to a GRN mutation, and one due to a MAPT mutation (R406W). Tracer retention was examined using a region-of-interest and voxel-wise approaches. Two individuals (bvFTD due to C9orf72) underwent postmortem neuropathological examination. Tracer binding was additionally assessed in vitro using [3H]RO948 autoradiography in six separate cases. RESULTS: [18F]RO948 retention across ROIs was clearly lower than in AD and comparable to that in Aß-negative cognitively unimpaired individuals. Only minor loci of tracer retention were seen in bvFTD; these did not overlap with the observed cortical atrophy in the cases, the expected pattern of atrophy, nor the expected or verified protein pathology distribution. Autoradiography analyses showed no specific [3H]RO948 binding. The R406W MAPT mutation carriers were clear exceptions with AD-like retention levels and specific in-vitro binding. CONCLUSION: [18F]RO948 uptake is not significantly increased in the majority of FTD patients, with a clear exception being specific MAPT mutations.

Amyloid and tau PET-positive cognitively unimpaired individuals are at high risk for future cognitive decline.

A major unanswered question in the dementia field is whether cognitively unimpaired individuals who harbor both Alzheimer's disease neuropathological hallmarks (that is, amyloid-ß plaques and tau neurofibrillary tangles) can preserve their cognition over time or are destined to decline. In this large multicenter amyloid and tau positron emission tomography (PET) study (n = 1,325), we examined the risk for future progression to mild cognitive impairment and the rate of cognitive decline over time among cognitively unimpaired individuals who were amyloid PET-positive (A+) and tau PET-positive (T+) in the medial temporal lobe (A+TMTL+) and/or in the temporal neocortex (A+TNEO-T+) and compared them with A+T- and A-T- groups. Cox proportional-hazards models showed a substantially increased risk for progression to mild cognitive impairment in the A+TNEO-T+ (hazard ratio (HR) = 19.2, 95% confidence interval (CI) = 10.9-33.7), A+TMTL+ (HR = 14.6, 95% CI = 8.1-26.4) and A+T- (HR = 2.4, 95% CI = 1.4-4.3) groups versus the A-T- (reference) group. Both A+TMTL+ (HR = 6.0, 95% CI = 3.4-10.6) and A+TNEO-T+ (HR = 7.9, 95% CI = 4.7-13.5) groups also showed faster clinical progression to mild cognitive impairment than the A+T- group. Linear mixed-effect models indicated that the A+TNEO-T+ (ß = -0.056 ± 0.005, T = -11.55, P < 0.001), A+TMTL+ (ß = -0.024 ± 0.005, T = -4.72, P < 0.001) and A+T- (ß = -0.008 ± 0.002, T = -3.46, P < 0.001) groups showed significantly faster longitudinal global cognitive decline compared to the A-T- (reference) group (all P < 0.001). Both A+TNEO-T+ (P < 0.001) and A+TMTL+ (P = 0.002) groups also progressed faster than the A+T- group. In summary, evidence of advanced Alzheimer's disease pathological changes provided by a combination of abnormal amyloid and tau PET examinations is strongly associated with short-term (that is, 3-5 years) cognitive decline in cognitively unimpaired individuals and is therefore of high clinical relevance.

Freely Available, Fully Automated AI-Based Analysis of Primary Tumour and Metastases of Prostate Cancer in Whole-Body [18F]-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 [18F]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' 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.

Myocardial perfusion by CMR coronary sinus flow shows sex differences and lowered perfusion at stress in patients with suspected microvascular angina.

BACKGROUND: Patients with chest pain may have normal coronary arteries and suffer from microvascular angina (MVA). The aim of this study was to determine if patients with suspected MVA have lower global myocardial perfusion (global MP) during adenosine stress compared with healthy controls and coronary artery disease (CAD) patients and to determine if there are sex differences in global MP. METHODS: Twenty-three patients with suspected MVA (66 ± 11 years), 19 CAD patients (69 ± 5 years) with stress-induced ischaemia and 24 healthy controls (61 ± 10 years) underwent cardiac magnetic resonance (CMR) including coronary sinus flow measurements and first-pass perfusion at rest and during adenosine stress. Global MP was quantified as coronary sinus flow normalized to left ventricular mass. RESULTS: Global perfusion was lower during stress in patients with suspected MVA (2.9 ± 1.0 ml/min/g) compared with healthy volunteers (3.7 ± 1.1 ml/min/g, p = 0.018), but higher compared with CAD patients (2.0 ± 0.9 ml/min/g, p = 0.019). Female controls had higher global MP than male controls both at rest (1.0 ± 0.3 vs. 0.7 ± 0.2 ml/min/g, p = 0.003) and during stress (4.4 ± 1.0 vs. 3.1 ± 0.6 ml/min/g, p = 0.001). Furthermore, females with suspected MVA showed higher global MP than males with suspected MVA (3.3 ± 1.0 vs. 2.4 ± 0.7, p = 0.04). CONCLUSIONS: Patients with suspected MVA have lower global MP at stress than healthy volunteers but higher than patients with CAD. Furthermore, there seems to be a sex difference in global MP at stress both in healthy volunteers and in patients with suspected MVA, with higher global MP in females, which implies a need for sex-specific normal limits when assessing quantitative MP.

Biomarker-Based Prediction of Longitudinal Tau Positron Emission Tomography in Alzheimer Disease.

Importance: There is currently no consensus as to which biomarkers best predict longitudinal tau accumulation at different clinical stages of Alzheimer disease (AD). Objective: To describe longitudinal [18F]RO948 tau positron emission tomography (PET) findings across the clinical continuum of AD and determine which biomarker combinations showed the strongest associations with longitudinal tau PET and best optimized clinical trial enrichment. Design, Setting, and Participants: This longitudinal cohort study consecutively enrolled amyloid-ß (Aß)-negative cognitively unimpaired (CU) participants, Aß-positive CU individuals, Aß-positive individuals with mild cognitive impairment (MCI), and individuals with AD dementia between September 2017 and November 2020 from the Swedish BioFINDER-2 (discovery cohort) and BioFINDER-1 (validation cohort) studies. Exposures: Baseline plasma and cerebrospinal fluid Aß42/Aß40, tau phosphorylated at threonine-217 (p-tau217), p-tau181 and neurofilament light, magnetic resonance imaging, amyloid PET ([18F]flutemetamol), and tau PET ([18F]RO948 in the BioFINDER-2 study; [18F]flortaucipir in the BioFINDER-1 study). Main Outcomes and Measures: Baseline tau PET standardized uptake value ratio (SUVR) and annual percent change in tau PET SUVR across regions of interest derived using a data-driven approach combining clustering and event-based modeling. Regression models were used to examine associations between individual biomarkers and longitudinal tau PET and to identify which combinations best predicted longitudinal tau PET. These combinations were then entered in a power analysis to examine how their use as an enrichment strategy would affect sample size in a simulated clinical trial. Results: Of 343 participants, the mean (SD) age was 72.56 (7.24) years, and 157 (51.1%) were female. The clustering/event-based modeling-based approach identified 5 regions of interest (stages). In Aß-positive CU individuals, the largest annual increase in tau PET SUVR was seen in stage I (entorhinal cortex, hippocampus, and amygdala; 4.04% [95% CI, 2.67%-5.32%]). In Aß-positive individuals with MCI and with AD dementia, the greatest increases were seen in stages II (temporal cortical regions; 4.45% [95% CI, 3.41%-5.49%]) and IV (certain frontal regions; 5.22% [95% CI, 3.95%-6.49%]), respectively. In Aß-negative CU individuals and those with MCI, modest change was seen in stage I (1.38% [95% CI, 0.78%-1.99%] and 1.80% [95% CI, 0.76%-2.84%], respectively). When looking at individual predictors and longitudinal tau PET in the stages that showed most change, plasma p-tau217 (R2 = 0.27, P < .005), tau PET (stage I baseline SUVR; R2 = 0.13, P < .05) and amyloid PET (R2 = 0.10, P < .05) were significantly associated with longitudinal tau PET in stage I in Aß-positive CU individuals. In Aß-positive individuals with MCI, plasma p-tau217 (R2 = 0.24, P < .005) and tau PET (stage II baseline SUVR; R2 = 0.44, P < .001) were significantly associated with longitudinal tau PET in stage II. Findings were replicated in BioFINDER-1 using longitudinal [18F]flortaucipir. For the power analysis component, plasma p-tau217 with tau PET resulted in sample size reductions of 43% (95% CI, 34%-46%; P < .005) in Aß-positive CU individuals and of 68% (95% CI, 61%-73%; P < .001) in Aß-positive individuals with MCI. Conclusions and Relevance: In trials using tau PET as the outcome, plasma p-tau217 with tau PET may prove optimal for enrichment in preclinical and prodromal AD. However, plasma p-tau217 was most important in preclinical AD, while tau PET was more important in prodromal AD.

Pulmonary perfusion and NYHA classification improve after cardiac resynchronization therapy.

BACKGROUND: Evaluation of cardiac resynchronization therapy (CRT) often includes New York Heart Association (NYHA) classification, and echocardiography. However, these measures have limitations. Perfusion gradients from ventilation/perfusion single-photon emission computed tomography (V/P SPECT) are related to left-heart filling pressures and have been validated against invasive right-heart catheterization. The aim was to assess if changes in perfusion gradients are associated with improvements in heart failure (HF) symptoms after CRT, and if they correlate with currently used diagnostic methods in the follow-up of patients with HF after receiving CRT. METHODS AND RESULTS: Nineteen patients underwent V/P SPECT, echocardiography, NYHA classification, and the quality-of-life scoring system "Minnesota living with HF" (MLWHF), before and after CRT. CRT caused improvement in perfusion gradients from V/P SPECT which were associated with improvements in NYHA classification (P = .0456), whereas improvements in end-systolic volume (LVESV) from echocardiography were not. After receiving CRT, the proportion of patients who improved was lower using LVESV (n = 7/19, 37%) than perfusion gradients (n = 13/19, 68%). Neither change in perfusion gradients nor LVESV was associated with changes in MLWHF (P = 1.0, respectively). CONCLUSIONS: Measurement of perfusion gradients from V/P SPECT is a promising quantitative user-independent surrogate measure of left-sided filling pressure in the assessment of CRT response in patients with HF.

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

BACKGROUND: In 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. METHODS: Twelve 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. RESULTS: Imaging 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%). CONCLUSIONS: Renal [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.

Accuracy of Tau Positron Emission Tomography as a Prognostic Marker in Preclinical and Prodromal Alzheimer Disease: A Head-to-Head Comparison Against Amyloid Positron Emission Tomography and Magnetic Resonance Imaging.

Importance: Tau positron emission tomography (PET) tracers have proven useful for the differential diagnosis of dementia, but their utility for predicting cognitive change is unclear. Objective: To examine the prognostic accuracy of baseline fluorine 18 (18F)-flortaucipir and [18F]RO948 (tau) PET in individuals across the Alzheimer disease (AD) clinical spectrum and to perform a head-to-head comparison against established magnetic resonance imaging (MRI) and amyloid PET markers. Design, Setting, and Participants: This prognostic study collected data from 8 cohorts in South Korea, Sweden, and the US from June 1, 2014, to February 28, 2021, with a mean (SD) follow-up of 1.9 (0.8) years. A total of 1431 participants were recruited from memory clinics, clinical trials, or cohort studies; 673 were cognitively unimpaired (CU group; 253 [37.6%] positive for amyloid-ß [Aß]), 443 had mild cognitive impairment (MCI group; 271 [61.2%] positive for Aß), and 315 had a clinical diagnosis of AD dementia (315 [100%] positive for Aß). Exposures: [18F]Flortaucipir PET in the discovery cohort (n = 1135) or [18F]RO948 PET in the replication cohort (n = 296), T1-weighted MRI (n = 1431), and amyloid PET (n = 1329) at baseline and repeated Mini-Mental State Examination (MMSE) evaluation. Main Outcomes and Measures: Baseline [18F]flortaucipir/[18F]RO948 PET retention within a temporal region of interest, MRI-based AD-signature cortical thickness, and amyloid PET Centiloids were used to predict changes in MMSE using linear mixed-effects models adjusted for age, sex, education, and cohort. Mediation/interaction analyses tested whether associations between baseline tau PET and cognitive change were mediated by baseline MRI measures and whether age, sex, and APOE genotype modified these associations. Results: Among 1431 participants, the mean (SD) age was 71.2 (8.8) years; 751 (52.5%) were male. Findings for [18F]flortaucipir PET predicted longitudinal changes in MMSE, and effect sizes were stronger than for AD-signature cortical thickness and amyloid PET across all participants (R2, 0.35 [tau PET] vs 0.24 [MRI] vs 0.17 [amyloid PET]; P < .001, bootstrapped for difference) in the Aß-positive MCI group (R2, 0.25 [tau PET] vs 0.15 [MRI] vs 0.07 [amyloid PET]; P < .001, bootstrapped for difference) and in the Aß-positive CU group (R2, 0.16 [tau PET] vs 0.08 [MRI] vs 0.08 [amyloid PET]; P < .001, bootstrapped for difference). These findings were replicated in the [18F]RO948 PET cohort. MRI mediated the association between [18F]flortaucipir PET and MMSE in the groups with AD dementia (33.4% [95% CI, 15.5%-60.0%] of the total effect) and Aß-positive MCI (13.6% [95% CI, 0.0%-28.0%] of the total effect), but not the Aß-positive CU group (3.7% [95% CI, -17.5% to 39.0%]; P = .71). Age (t = -2.28; P = .02), but not sex (t = 0.92; P = .36) or APOE genotype (t = 1.06; P = .29) modified the association between baseline [18F]flortaucipir PET and cognitive change, such that older individuals showed faster cognitive decline at similar tau PET levels. Conclusions and Relevance: The findings of this prognostic study suggest that tau PET is a promising tool for predicting cognitive change that is superior to amyloid PET and MRI and may support the prognostic process in preclinical and prodromal stages of AD.

Post-reconstruction enhancement of [18F]FDG PET images with a convolutional neural network.

BACKGROUND: The aim of the study was to develop and test an artificial intelligence (AI)-based method to improve the quality of [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) images. METHODS: A convolutional neural network (CNN) was trained by using pairs of excellent (acquisition time of 6 min/bed position) and standard (acquisition time of 1.5 min/bed position) or sub-standard (acquisition time of 1 min/bed position) images from 72 patients. A test group of 25 patients was used to validate the CNN qualitatively and quantitatively with 5 different image sets per patient: 4 min/bed position, 1.5 min/bed position with and without CNN, and 1 min/bed position with and without CNN. RESULTS: Difference in hotspot maximum or peak standardized uptake value between the standard 1.5 min and 1.5 min CNN images fell short of significance. Coefficient of variation, the noise level, was lower in the CNN-enhanced images compared with standard 1 min and 1.5 min images. Physicians ranked the 1.5 min CNN and the 4 min images highest regarding image quality (noise and contrast) and the standard 1 min images lowest. CONCLUSIONS: AI can enhance [18F]FDG-PET images to reduce noise and increase contrast compared with standard images whilst keeping SUVmax/peak stability. There were significant differences in scoring between the 1.5 min and 1.5 min CNN image sets in all comparisons, the latter had higher scores in noise and contrast. Furthermore, difference in SUVmax and SUVpeak fell short of significance for that pair. The improved image quality can potentially be used either to provide better images to the nuclear medicine physicians or to reduce acquisition time/administered activity.

Tumor detection of 18F-PSMA-1007 in the prostate gland in patients with prostate cancer using prostatectomy specimens as reference method.

Prostate-specific membrane antigen (PSMA) radiopharmaceuticals used with positron emission tomography/computed tomography (PET-CT) are a promising tool for managing patients with prostate cancer. This study aimed to determine the accuracy of 18F-PSMA-1007 PET-CT for detecting tumors in the prostate gland using radical prostatectomy (RP) specimens as a reference method and to determine whether a correlation exists between 18F-PSMA-1007 uptake and the International Society of Urological Pathology (ISUP) grade and prostate specific antigen (PSA) levels at diagnosis. Methods: Thirty-nine patients referred for 18F-PSMA-1007 PET-CT for initial staging and who underwent RP within four months were retrospectively included. Uptake of 18F-PSMA-1007 indicative of cancer was assessed and maximum standardized uptake values (SUVmax) and total lesion uptake (TLU) were calculated for the index tumor. Histopathology was assessed from RP specimens. True positive, false negative, and false positive lesions were calculated. Results: In 94.9% of patients, the index tumor was correctly identified with PET. SUVmax was significantly higher in the tumors vs normal prostate tissue, but no significant differences were found between different ISUP grades and SUVmax There was a poor correlation between PSA at diagnosis and SUVmax (r=0.23) and moderate agreement between PSA at diagnosis and TLU (r=0.67). When all tumors (also non-index tumors) were considered, many small tumors (approx. 1-2 mm) were not detected with PET. Conclusion: 18F-PSMA-1007 PET-CT performs well in correctly identifying the index tumor in patients with intermediate to high-risk prostate cancer. Approximately 5% of the index tumors were missed by PET, which agrees with previous studies.

Appropriate coronary revascularization can be accomplished if myocardial perfusion is quantified by positron emission tomography prior to treatment decision.

BACKGROUND: Many patients undergo percutaneous coronary intervention (PCI) without the use of non-invasive stress testing prior to treatment. The aim of this study was to determine the potential added value of guiding revascularization by quantitative assessment of myocardial perfusion prior to intervention. METHODS AND RESULTS: Thirty-three patients (10 females) with suspected or established CAD who had been referred for a clinical coronary angiography (CA) with possibility for PCI were included. Adenosine stress and rest 13N-NH3 PET, cardiac magnetic resonance (CMR), and cardiopulmonary exercise test were performed 4 ± 3 weeks before and 5 ± 1 months after CA. The angiographer was blinded to the PET and CMR results. Myocardial flow reserve (MFR) < 2.0 by PET was considered abnormal. A PCI was performed in 19/33 patients. In 41% (11/27) of the revascularized vessel territories, a normal regional MFR was found prior to the PCI and no improvement in MFR was found at follow-up (P = 0.9). However, vessel territories with regional MFR < 2.0 at baseline improved significantly after PCI (P = 0.003). Of the 14 patients not undergoing PCI, four had MFR < 2.0 in one or more coronary territories. CONCLUSION: Assessment of quantitative myocardial perfusion prior to revascularization could lead to more appropriate use of CA when managing patients with stable CAD.

The impact of demographic, clinical, genetic, and imaging variables on tau PET status.

PURPOSE: A substantial proportion of amyloid-ß (Aß)+ patients with clinically diagnosed Alzheimer's disease (AD) dementia and mild cognitive impairment (MCI) are tau PET-negative, while some clinically diagnosed non-AD neurodegenerative disorder (non-AD) patients or cognitively unimpaired (CU) subjects are tau PET-positive. We investigated which demographic, clinical, genetic, and imaging variables contributed to tau PET status. METHODS: We included 2338 participants (430 Aß+ AD dementia, 381 Aß+ MCI, 370 non-AD, and 1157 CU) who underwent [18F]flortaucipir (n = 1944) or [18F]RO948 (n = 719) PET. Tau PET positivity was determined in the entorhinal cortex, temporal meta-ROI, and Braak V-VI regions using previously established cutoffs. We performed bivariate binary logistic regression models with tau PET status (positive/negative) as dependent variable and age, sex, APOEε4, Aß status (only in CU and non-AD analyses), MMSE, global white matter hyperintensities (WMH), and AD-signature cortical thickness as predictors. Additionally, we performed multivariable binary logistic regression models to account for all other predictors in the same model. RESULTS: Tau PET positivity in the temporal meta-ROI was 88.6% for AD dementia, 46.5% for MCI, 9.5% for non-AD, and 6.1% for CU. Among Aß+ participants with AD dementia and MCI, lower age, MMSE score, and AD-signature cortical thickness showed the strongest associations with tau PET positivity. In non-AD and CU participants, presence of Aß was the strongest predictor of a positive tau PET scan. CONCLUSION: We identified several demographic, clinical, and neurobiological factors that are important to explain the variance in tau PET retention observed across the AD pathological continuum, non-AD neurodegenerative disorders, and cognitively unimpaired persons.

Image reconstruction methods affect software-aided assessment of pathologies of [18F]flutemetamol and [18F]FDG brain-PET examinations in patients with neurodegenerative diseases.

PURPOSE: To assess how some of the new developments in brain positron emission tomography (PET) image reconstruction affect quantitative measures and software-aided assessment of pathology in patients with neurodegenerative diseases. METHODS: PET data were grouped into four cohorts: prodromal Alzheimer's disease patients and controls receiving [18F]flutemetamol, and neurodegenerative disease patients and controls receiving [18F]FDG PET scans. Reconstructed images were obtained by ordered-subsets expectation maximization (OSEM; 3 iterations (i), 16/34 subsets (s), 3/5-mm filter, ±time-of-flight (TOF), ±point-spread function (PSF)) and block-sequential regularized expectation maximization (BSREM; TOF, PSF, ß-value 75-300). Standardized uptake value ratios (SUVR) and z-scores were calculated (CortexID Suite, GE Healthcare) using cerebellar gray matter, pons, whole cerebellum and whole brain as reference regions. RESULTS: In controls, comparable results to the normal database were obtained with OSEM 3i/16 s 5-mm reconstruction. TOF, PSF and BSREM either increased or decreased the relative uptake difference to the normal subjects' database within the software, depending on the tracer and chosen reference area, i.e. resulting in increased absolute z-scores. Normalizing to pons and whole brain for [18F]flutemetamol and [18F]FDG, respectively, increased absolute differences between reconstructions methods compared to normalizing to cerebellar gray matter and whole cerebellum when applying TOF, PSF and BSREM. CONCLUSIONS: Software-aided assessment of patient pathologies should be used with caution when employing other image reconstruction methods than those used for acquisition of the normal database.

Diagnostic Performance of RO948 F 18 Tau Positron Emission Tomography in the Differentiation of Alzheimer Disease From Other Neurodegenerative Disorders.

Importance: The diagnostic performance of second-generation tau positron emission tomographic (PET) tracers is not yet known. Objective: To examine the novel tau PET tracer RO948 F 18 ([18F]RO948) performance in discriminating Alzheimer disease (AD) from non-AD neurodegenerative disorders. Design, Setting, and Participants: In this diagnostic study, 613 participants in the Swedish BioFINDER-2 study were consecutively enrolled in a prospective cross-sectional study from September 4, 2017, to August 28, 2019. Participants included 257 cognitively unimpaired controls, 154 patients with mild cognitive impairment, 100 patients with AD dementia, and 102 with non-AD neurodegenerative disorders. Evaluation included a comparison of tau PET tracer [18F]RO948 with magnetic resonance imaging (MRI) and cerebrospinal fluid and a head-to-head comparison between [18F]RO948 and flortaucipir F 18 ([18F]flortaucipir) in patients with semantic variant primary progressive aphasia (svPPA). Exposures: [18F]RO948 (all patients) and [18F]flortaucipir (3 patients with svPPA) tau PET; MRI (hippocampal volume, composite temporal lobe cortical thickness, whole-brain cortical thickness) and cerebrospinal fluid measures (p-tau181 and amyloid Aß42 and Aß40 ratio[Aß42/Aß40], and Aß42/p-tau181 ratio). Main Outcomes and Measures: Standard uptake value ratios (SUVRs) in 4 predefined regions of interest (ROIs) reflecting Braak staging scheme for tau pathology and encompass I-II (entorhinal cortex), III-IV (inferior/middle temporal, fusiform gyrus, parahippocampal cortex, and amygdala), I-IV, and V-VI (widespread neocortical areas), area under the receiver operating characteristic curve (AUC) values, and subtraction images between [18F]RO948 and [18F]flortaucipir. Results: Diagnostic groups among the 613 participants included cognitively unimpaired (mean [SD] age, 65.8 [12.1] years; 117 men [46%]), mild cognitive impairment (age, 70.8 [8.3] years; 82 men [53%]), AD dementia (age, 73.5 [6.7] years; 57 men [57%]), and non-AD disorders (age, 70.5 [8.6] years; 41 men [40%]). Retention of [18F]RO948 was higher in AD dementia compared with all other diagnostic groups. [18F]RO948 could distinguish patients with AD dementia from individuals without cognitive impairment and those with non-AD disorders, and the highest AUC was obtained using the I-IV ROI (AUC = 0.98; 95% CI, 0.96-0.99 for AD vs no cognitive impairment and AUC = 0.97; 95% CI, 0.95-0.99 for AD vs non-AD disorders), which outperformed MRI (highest AUC = 0.91 for AD vs no cognitive impairment using whole-brain thickness, and AUC = 0.80 for AD vs non-AD disorders using temporal lobe thickness) and cerebrospinal fluid measures (highest AUC = 0.94 for AD vs no cognitive impairment using Aß42/p-tau181, and AUC = 0.93 for AD vs non-AD disorders using Aß42/Aß40). Generally, tau PET positivity using [18F]RO948 was observed only in Aß-positive cases or in MAPT R406W mutation carriers. Retention of [18F]RO948 was not pronounced in patients with svPPA, and head-to-head comparison revealed lower temporal lobe uptake than with [18F]flortaucipir. Conclusions and Relevance: In this study, elevated [18F]RO948 SUVRs were most often seen among Aß-positive cases, which suggests that [18F]RO948 has high specificity for AD-type tau and highlights its potential as a diagnostic marker in the differential diagnosis of AD.

Qualitative assessments of myocardial ischemia by cardiac MRI and coronary stenosis by invasive coronary angiography in relation to quantitative perfusion by positron emission tomography in patients with known or suspected stable coronary artery disease.

BACKGROUND: To relate findings of qualitative evaluation of first-pass perfusion-CMR and anatomical evaluation on coronary angiography (CA) to the reference standard of quantitative perfusion, cardiac PET, in patients with suspected or known stable coronary artery disease (CAD). METHODS AND RESULTS: Forty-one patients referred for CA due to suspected stable CAD, prospectively performed adenosine stress/rest first-pass perfusion-CMR as well as 13N-NH3 PET on the same day, 4 ± 3 weeks before CA. Angiographers were blinded to PET and CMR results. Regional myocardial flow reserve (MFR) < 2.0 on PET was considered pathological. Vessel territories with stress-induced ischemia by CMR or vessels with stenosis needing revascularization had a significantly lower MFR compared to those with no regional stress-induced ischemia or vessels not needing revascularization (P < 0.001). In 4 of 123 vessel territories with stress-induced ischemia by CMR, PET showed a normal MFR. In addition, 12 of 123 vessels that underwent intervention showed normal MFR assessed by PET. CONCLUSION: The limited performance of qualitative assessment of presence of stable CAD with CMR and CA, when related to quantitative 13N-NH3 cardiac PET, shows the need for fully quantitative assessment of myocardial perfusion and the use of invasive flow reserve measurements for CA, to confirm the need of elective revascularization.