Abnormal Positron Emission Tomography Research Articles

Comparative effectiveness of positron emission tomography and single-photon emission computed tomography myocardial perfusion imaging for predicting risk in patients with cardiometabolic disease

BackgroundThe epidemiology of coronary artery disease (CAD) has shifted, with increasing prevalence of cardiometabolic disease and decreasing findings of obstructive CAD on myocardial perfusion imaging (MPI). Coronary microvascular dysfunction (CMD), defined as impaired myocardial flow reserve (MFR) by positron emission tomography (PET), has emerged as a key mediator of risk. We aimed to assess whether PET MFR provides additive value for risk stratification of cardiometabolic disease patients compared with single-photon emission computed tomography (SPECT) MPI. MethodsWe retrospectively followed patients referred for PET, exercise SPECT, or pharmacologic SPECT MPI with cardiometabolic disease (obesity, diabetes, or chronic kidney disease) and without known CAD. We compared rates and hazards of composite major adverse cardiovascular events (MACEs) (annualized cardiac mortality or acute myocardial infarction) among propensity-matched PET and SPECT patients using Poisson and Cox regression. Normal SPECT was defined as a total perfusion deficit (TPD) of <5%, reflecting the absence of obstructive CAD. Normal PET was defined as a TPD of <5% plus an MFR of ≥2.0. ResultsAmong 21,544 patients referred from 2006 to 2020, cardiometabolic disease was highly prevalent (PET: 2308 [67%], SPECT: 9984 [55%]) and higher among patients referred to PET (P < 0.001). Obstructive CAD findings (TPD > 5%) were uncommon (PET: 21% and SPECT: 11%). Conversely, impaired MFR on PET (<2.0) was common (62%). In a propensity-matched analysis over a median 6.4-year follow-up, normal PET identified low-risk (0.9%/year MACE) patients, and abnormal PET identified high-risk (4.2%/year MACE) patients with cardiometabolic disease; conversely, those with normal pharmacologic SPECT remained moderate-risk (1.6%/year, P < 0.001 compared to normal PET). ConclusionsCardiometabolic disease is common among patients referred for MPI and is associated with a heterogenous level of risk. Compared with pharmacologic SPECT, PET with MFR can detect nonobstructive CAD including CMD and can more accurately discriminate low-risk from higher-risk individuals.

Prognostic value of a novel artificial intelligence-based coronary CTA-derived ischemia algorithm among patients with normal or abnormal myocardial perfusion

BackgroundAmong patients with obstructive coronary artery disease (CAD) on coronary computed tomography angiography (CTA), downstream positron emission tomography (PET) perfusion imaging can be performed to assess the presence of myocardial ischemia. A novel artificial-intelligence-guided quantitative computed tomography ischemia algorithm (AI-QCTischemia) aims to predict ischemia directly from coronary CTA images. We aimed to study the prognostic value of AI-QCTischemia among patients with obstructive CAD on coronary CTA and normal or abnormal downstream PET perfusion. MethodsAI-QCTischemia was calculated by blinded analysts among patients from the retrospective coronary CTA cohort at Turku University Hospital, Finland, with obstructive CAD on initial visual reading (diameter stenosis ≥50%) being referred for downstream 15O-H2O-PET adenosine stress perfusion imaging. All coronary arteries with their side branches were assessed by AI-QCTischemia. Absolute stress myocardial blood flow ≤2.3 ​ml/g/min in ≥2 adjacent segments was considered abnormal. The primary endpoint was death, myocardial infarction, or unstable angina pectoris. The median follow-up was 6.2 [IQR 4.4–8.3] years. Results662 of 768 (86%) patients had conclusive AI-QCTischemia result. In patients with normal 15O-H2O-PET perfusion, an abnormal AI-QCTischemia result (n ​= ​147/331) vs. normal AI-QCTischemia result (n ​= ​184/331) was associated with a significantly higher crude and adjusted rates of the primary endpoint (adjusted HR 2.47, 95% CI 1.17–5.21, p ​= ​0.018). This did not pertain to patients with abnormal 15O-H2O-PET perfusion (abnormal AI-QCTischemia result (n ​= ​269/331) vs. normal AI-QCTischemia result (n ​= ​62/331); adjusted HR 1.09, 95% CI 0.58–2.02, p ​= ​0.794) (p-interaction ​= ​0.039). ConclusionAmong patients with obstructive CAD on coronary CTA referred for downstream 15O-H2O-PET perfusion imaging, AI-QCTischemia showed incremental prognostic value among patients with preserved perfusion by 15O-H2O-PET imaging, but not among those with reduced perfusion.

Plasma biomarkers of Alzheimer's disease in the continuum of dementia with Lewy bodies.

Patients with dementia with Lewy bodies (DLB) may have Alzheimers disease (AD) pathology that can be detected by plasma biomarkers. Our objective was to evaluate plasma biomarkers of AD and their association with positron emission tomography (PET) biomarkers of amyloid and tau deposition in the continuum of DLB, starting from prodromal stages of the disease. The cohort included patients with isolated rapid eye movement (REM) sleep behavior disorder (iRBD), mild cognitive impairment with Lewy bodies (MCI-LB), or DLB, with a concurrent blood draw and PET scans. Abnormal levels of plasma glial fibrillary acidic protein (GFAP) were found at the prodromal stage of MCI-LB in association with increased amyloid PET. Abnormal levels of plasma phosphorylated tau (p-tau)-181 and neurofilament light (NfL) were found at the DLB stage. Plasma p-tau-181 showed the highest accuracy in detecting abnormal amyloid and tau PET in patients with DLB. The range of AD co-pathology can be detected with plasma biomarkers in the DLB continuum, particularly with plasma p-tau-181 and GFAP.

The Role of PET Imaging in Patients with Prion Disease: A Literature Review.

Prion diseases are rare, rapidly progressive, and fatal incurable degenerative brain disorders caused by the misfolding of a normal protein called PrPC into an abnormal protein called PrPSc. Their highly variable clinical presentation mimics various degenerative and non-degenerative brain disorders, making diagnosis a significant challenge for neurologists. Currently, definitive diagnosis relies on post-mortem examination of nervous tissue to detect the pathogenic prion protein. The current diagnostic criteria are limited. While structural magnetic resonance imaging (MRI) remains the gold standard imaging modality for Creutzfeldt-Jakob disease (CJD) diagnosis, positron emission tomography (PET) using 18fluorine-fluorodeoxyglucose (18F-FDG) and other radiotracers have demonstrated promising potential in the diagnostic assessment of prion disease. In this context, a comprehensive and updated review exclusively focused on PET imaging in prion diseases is still lacking. We review the current value of PET imaging with 18F-FDG and non-FDG tracers in the diagnostic management of prion diseases. From the collected data, 18F-FDG PET mainly reveals cortical and subcortical hypometabolic areas in prion disease, although fails to identify typical pattern or laterality abnormalities to differentiate between genetic and sporadic prion diseases. Although the rarity of prion diseases limits the establishment of a definitive hypometabolism pattern, this review reveals some more prevalent 18F-FDG patterns associated with each disease subtype. Interestingly, in both sporadic and genetic prion diseases, the hippocampus does not show significant glucose metabolism alterations, appearing as a useful sign in the differential diagnosis with other neurodegenerative disease. In genetic prion disease forms, PET abnormality precedes clinical manifestation. Discordant diagnostic value for amyloid tracers among different prion disease subtypes was observed, needing further investigation. PET has emerged as a potential valuable tool in the diagnostic armamentarium for CJD. Its ability to visualize functional and metabolic brain changes provides complementary information to structural MRI, aiding in the early detection and confirmation of CJD.

Diagnostic Accuracy of a Plasma Phosphorylated Tau 217 Immunoassay for Alzheimer Disease Pathology

Phosphorylated tau (p-tau) is a specific blood biomarker for Alzheimer disease (AD) pathology, with p-tau217 considered to have the most utility. However, availability of p-tau217 tests for research and clinical use has been limited. Expanding access to this highly accurate AD biomarker is crucial for wider evaluation and implementation of AD blood tests. To determine the utility of a novel and commercially available immunoassay for plasma p-tau217 to detect AD pathology and evaluate reference ranges for abnormal amyloid β (Aβ) and longitudinal change across 3 selected cohorts. This cohort study examined data from 3 single-center observational cohorts: cross-sectional and longitudinal data from the Translational Biomarkers in Aging and Dementia (TRIAD) cohort (visits October 2017-August 2021) and Wisconsin Registry for Alzheimer's Prevention (WRAP) cohort (visits February 2007-November 2020) and cross-sectional data from the Sant Pau Initiative on Neurodegeneration (SPIN) cohort (baseline visits March 2009-November 2021). Participants included individuals with and without cognitive impairment grouped by amyloid and tau (AT) status using PET or CSF biomarkers. Data were analyzed from February to June 2023. Magnetic resonance imaging, Aβ positron emission tomography (PET), tau PET, cerebrospinal fluid (CSF) biomarkers (Aβ42/40 and p-tau immunoassays), and plasma p-tau217 (ALZpath pTau217 assay). Accuracy of plasma p-tau217 in detecting abnormal amyloid and tau pathology, longitudinal p-tau217 change according to baseline pathology status. The study included 786 participants (mean [SD] age, 66.3 [9.7] years; 504 females [64.1%] and 282 males [35.9%]). High accuracy was observed in identifying elevated Aβ (area under the curve [AUC], 0.92-0.96; 95% CI, 0.89-0.99) and tau pathology (AUC, 0.93-0.97; 95% CI, 0.84-0.99) across all cohorts. These accuracies were comparable with CSF biomarkers in determining abnormal PET signal. The detection of abnormal Aβ pathology using a 3-range reference yielded reproducible results and reduced confirmatory testing by approximately 80%. Longitudinally, plasma p-tau217 values showed an annual increase only in Aβ-positive individuals, with the highest increase observed in those with tau positivity. This study found that a commercially available plasma p-tau217 immunoassay accurately identified biological AD, comparable with results using CSF biomarkers, with reproducible cut-offs across cohorts. It detected longitudinal changes, including at the preclinical stage.

32 Prediction of Seizure Outcome with Presurgical IAT, MRI, and PET in Patients with Temporal Lobe Epilepsy Undergoing Surgery

Objective:Anterior temporal lobectomy is a common surgical approach for medication-resistant temporal lobe epilepsy (TLE). Prior studies have shown inconsistent findings regarding the utility of presurgical intracarotid sodium amobarbital testing (IAT; also known as Wada test) and neuroimaging in predicting postoperative seizure control. In the present study, we evaluated the predictive utility of IAT, as well as structural magnetic resonance imaging (MRI) and positron emission tomography (PET), on long-term (3-years) seizure outcome following surgery for TLE.Participants and Methods:Patients consisted of 107 adults (mean age=38.6, SD=12.2; mean education=13.3 years, SD=2.0; female=47.7%; White=100%) with TLE (mean epilepsy duration =23.0 years, SD=15.7; left TLE surgery=50.5%). We examined whether demographic, clinical (side of resection, resection type [selective vs. non-selective], hemisphere of language dominance, epilepsy duration), and presurgical studies (normal vs. abnormal MRI, normal vs. abnormal PET, correctly lateralizing vs. incorrectly lateralizing IAT) were associated with absolute (cross-sectional) seizure outcome (i.e., freedom vs. recurrence) with a series of chi-squared and t-tests. Additionally, we determined whether presurgical evaluations predicted time to seizure recurrence (longitudinal outcome) over a three-year period with univariate Cox regression models, and we compared survival curves with Mantel-Cox (log rank) tests.Results:Demographic and clinical variables (including type [selective vs. whole lobectomy] and side of resection) were not associated with seizure outcome. No associations were found among the presurgical variables. Presurgical MRI was not associated with cross-sectional (OR=1.5, p=.557, 95% CI=0.4-5.7) or longitudinal (HR=1.2, p=.641, 95% CI=0.4-3.9) seizure outcome. Normal PET scan (OR= 4.8, p=.045, 95% CI=1.0-24.3) and IAT incorrectly lateralizing to seizure focus (OR=3.9, p=.018, 95% CI=1.2-12.9) were associated with higher odds of seizure recurrence. Furthermore, normal PET scan (HR=3.6, p=.028, 95% CI =1.0-13.5) and incorrectly lateralized IAT (HR= 2.8, p=.012, 95% CI=1.2-7.0) were presurgical predictors of earlier seizure recurrence within three years of TLE surgery. Log rank tests indicated that survival functions were significantly different between patients with normal vs. abnormal PET and incorrectly vs. correctly lateralizing IAT such that these had seizure relapse five and seven months earlier on average (respectively).Conclusions:Presurgical normal PET scan and incorrectly lateralizing IAT were associated with increased risk of post-surgical seizure recurrence and shorter time-to-seizure relapse.

Management and Outcomes of Hodgkin Lymphoma Patients Who Achieve Partial Metabolic Response on PET Scans Post-Chemotherapy

Optimal management of patients with Hodgkin Lymphoma (HL) who do not achieve PET (positron emission tomography) complete metabolic response after primary systemic therapy is unclear. Options vary significantly and include radiation therapy (RT) to localized sites of PET avid disease, salvage chemotherapy followed by autologous stem-cell transplantation (ASCT), or observation with serial imaging. This multi-center study sought to investigate the management approaches and outcomes for HL patients who achieved partial metabolic response after primary systemic therapy. In this retrospective study, patients diagnosed with HL were identified from the electronic medical records database of two large academic centers between January 2009 and September 2021. PET scan results following initial chemotherapy were reviewed and responses were categorized using International Working Group (IWG) criteria, with the initial staging imaging being used as the reference against which response was evaluated. We performed descriptive analysis of demographic and clinical characteristics of the population and Kaplan-Meier estimates were used to determine progression-free survival (PFS). The charts of 1,093 HL patients were reviewed. A total of 765 patients had a post chemotherapy PET scan with 57 of those showing partial metabolic response. Among these 57 patients, 31 (54%) were male, the median age at diagnosis was 31 (range:18-74), and the median length of follow up was 1.6 years (average 2.9 years). Five percent stage I, 32% stage II, 23% stage III, and 40% stage IV. Typical initial chemotherapy included ABVD, ABVD switched to BEACOPP due to abnormal interim PET, and AVD with Brentuximab. Among all patients with metabolic partial response to chemotherapy, the 2-year PFS was 72.8% (95% CI = 60.9-87%). Thirty-three of these patients (58%) were treated with planned radiation therapy alone, and 2-year PFS was 80.7% (95% CI = 66.6-97.9%). For those who did not receive radiation as part of their treatment, progression rate was 38% at 2 years. To our knowledge, this is the largest series of HL patients with partial metabolic response following primary chemotherapy. Our preliminary analysis showed that treatment with radiation was associated with good PFS at 2 years and many of those treated with radiation alone were cured.

18F]DPA-714 PET Imaging in the Presurgical Evaluation of Patients With Drug-Resistant Focal Epilepsy.

Translocator protein 18 kDa (TSPO) PET imaging is used to monitor glial activation. Recent studies have proposed TSPO PET as a marker of the epileptogenic zone (EZ) in drug-resistant focal epilepsy (DRFE). This study aims to assess the contributions of TSPO imaging using [18F]DPA-714 PET and [18F]FDG PET for localizing the EZ during presurgical assessment of DRFE, when phase 1 presurgical assessment does not provide enough information. We compared [18F]FDG and [18F]DPA-714 PET images of 23 patients who had undergone a phase 1 presurgical assessment, using qualitative visual analysis and quantitative analysis, at both the voxel and the regional levels. PET abnormalities (increase in binding for [18F]DPA-714 vs decrease in binding for [18F]FDG) were compared with clinical hypotheses concerning the localization of the EZ based on phase 1 presurgical assessment. The additional value of [18F]DPA-714 PET imaging to [18F]FDG for refining the localization of the EZ was assessed. To strengthen the visual analysis, [18F]DPA-714 PET imaging was also reviewed by 2 experienced clinicians blind to the EZ location. The study included 23 patients. Visual analysis of [18F]DPA-714 PET was significantly more accurate than [18F]FDG PET to both, show anomalies (95.7% vs 56.5%, p = 0.022), and provide additional information to refine the EZ localization (65.2% vs 17.4%, p = 0.019). All 10 patients with normal [18F]FDG PET had anomalies when using [18F]DPA-714 PET. The additional value of [18F]DPA-714 PET seemed to be greater in patients with normal brain MRI or with neocortical EZ (especially if insula is involved). Regional analysis of [18F]DPA-714 and [18F]FDG PET provided similar results. However, using voxel-wise analysis, [18F]DPA-714 was more effective than [18F]FDG for unveiling clusters whose localization was more often consistent with the EZ hypothesis (87.0% vs 39.1%, p = 0.019). Nonrelevant bindings were seen in 14 of 23 patients in visual analysis and 9 patients of 23 patients in voxel-wise analysis. [18F]DPA-714 PET imaging provides valuable information for presurgical assessments of patients with DRFE. TSPO PET could become an additional tool to help to the localization of the EZ, especially in patients with negative [18F]FDG PET. Eudract 2017-003381-27. Inclusion of the first patient: September 24, 2018. This study provides Class IV evidence on the utility of [18F]DPA-714 PET compared with [18F]FDG PET in identifying the epileptic zone in patients undergoing phase 1 presurgical evaluation for intractable epilepsy.

Does financial hardship associate with abnormal quantitative myocardial perfusion and major adverse cardiovascular event?

BackgroundData on impact of financial hardship on coronary artery disease (CAD) remain incomplete. MethodsConsecutive subjects referred for clinical rest/stress cardiac positron emission tomography (PET) were enrolled. Financial hardship is defined as patients’ inability to pay for their out-of-pocket expense for cardiac PET. Abnormal cardiac PET is defined as at least moderate relative perfusion defects at stress involving > 10% of the left ventricle or global coronary flow reserve ≤ 2.0. Patients were followed for major adverse cardiovascular event (MACE) comprised of all-cause mortality, non-fatal myocardial infarction, and late coronary revascularization. ResultsWe analyzed a total of 4173 patients with mean age 65.6 ± 11.3 years, 72.2% men, and 93.6% reported as having medical insurance. Of these, 504 (12.1%) patients had financial hardship. On multivariable analysis, financial hardship associated with abnormal cardiac PET (odds ratio 1.377, p = 0.004) and MACE (hazard ratio 1.432, p = 0.010) and its association with MACE was mostly through direct effect with small proportion mediated by abnormal cardiac PET or known CAD. ConclusionAmong patients referred for cardiac rest/stress PET, financial hardship independently associates with myocardial perfusion abnormalities and MACE; however, its effect on MACE is largely not mediated by abnormal myocardial perfusion or known CAD suggesting distinct impact of financial hardship beyond traditional risk factors and CAD that deserves attention and intervention to effectively reduced adverse outcomes. Having medical insurance does not consistently protect from financial hardship and a more preventive-oriented restructuring may provide better outcomes at lower cost.

Danish study of Non-Invasive Testing in Coronary Artery Disease 3 (Dan-NICAD 3): study design of a controlled study on optimal diagnostic strategy

IntroductionCurrent guideline recommend functional imaging for myocardial ischaemia if coronary CT angiography (CTA) has shown coronary artery disease (CAD) of uncertain functional significance. However, diagnostic accuracy of selective myocardial perfusion...

Novel Approach for Assessing Postinfarct Myocardial Injury and Inflammation Using Hybrid Somatostatin Receptor Positron Emission Tomography/Magnetic Resonance Imaging.

Novel Approach for Assessing Postinfarct Myocardial Injury and Inflammation Using Hybrid Somatostatin Receptor Positron Emission Tomography/Magnetic Resonance Imaging.

Intrinsic and secondary epileptogenicity in focal cortical dysplasia type II.

Favorable seizure outcome is reported following resection of bottom-of-sulcus dysplasia (BOSD). We assessed the distribution of epileptogenicity and dysplasia in and around BOSD to better understand this clinical outcome and the optimal surgical approach. We studied 27 children and adolescents with magnetic resonance imaging (MRI)-positive BOSD who underwent epilepsy surgery; 85% became seizure-free postresection (median=5.0 years follow-up). All patients had resection of the dysplastic sulcus, and 11 had additional resection of the gyral crown (GC) or adjacent gyri (AG). Markers of epileptogenicity were relative cortical hypometabolism on preoperative 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET), and spiking, ripples, fast ripples, spike-high-frequency oscillation cross-rate, and phase amplitude coupling (PAC) on preresection and postresection electrocorticography (ECoG), all analyzed at the bottom-of-sulcus (BOS), top-of-sulcus (TOS), GC, and AG. Markers of dysplasia were increased cortical thickness on preoperative MRI, and dysmorphic neuron density and variant allele frequency of somatic MTOR mutations in resected tissue, analyzed at similar locations. Relative cortical metabolism was significantly reduced and ECoG markers were significantly increased at the BOS compared to other regions. Apart from spiking and PAC, which were greater at the TOS compared to the GC, there were no significant differences in PET and other ECoG markers between the TOS, GC, and AG, suggesting a cutoff of epileptogenicity at the TOS rather than a tapering gradient on the cortical surface. MRI and tissue markers of dysplasia were all maximal in the BOS, reduced in the TOS, and mostly absent in the GC. Spiking and PAC reduced significantly over the GC after resection of the dysplastic sulcus. These findings support the concept that dysplasia and intrinsic epileptogenicity are mostly limited to the dysplastic sulcus in BOSD and support resection or ablation confined to the MRI-visible lesion as a first-line surgical approach. 18 F-FDG PET and ECoG abnormalities in surrounding cortex seem to be secondary phenomena.

The relationship of soluble p‐tau isoforms with brain amyloid and tau deposition in sporadic AD

AbstractBackgroundHyperphosphorylated tau isoforms (p‐tau) in cerebrospinal fluid (CSF) and plasma represent promising measures to monitor Alzheimer disease (AD) pathological changes. Brain amyloid deposition precedes tau aggregation and associated clinical decline by two decades. Several CSF and plasma p‐tau isoforms have been described as potential surrogates for tau Positron Emission Tomography (PET) imaging, but p‐tau isoforms have a strong association with amyloid PET, and increase without tau pathology. In this study, we investigated the relationship between multiple CSF p‐tau isoforms and brain imaging measures in the Knight ADRC cohort.MethodWe analyzed 10 p‐tau isoforms by mass spectrometry in 1932 CSF samples (1173 participants). Associated data includes 1250 amyloid PET and 442 tau PET scans, as well as CSF Aβ42/Aβ40 by immunoassay for all samples. We measured phosphorylation occupancies (ptau/tau) at T111, T153, T175, T181, S199, S202, T205, S208, T217 and T231, together with corresponding p‐tau and tau concentrations. We compared the accuracy of CSF p‐tau isoforms in predicting amyloid PET and tau PET status stratified according to amyloid PET, tau PET and/or Clinical Dementia Rating (CDR) status.ResultsPT217/T217 best‐predicted abnormal amyloid PET (AUROC=0.980) or CSF Aβ42/Aβ40 (AUC=0.954). PT217/T217 predicted brain amyloidosis in asymptomatic and symptomatic participants with similar accuracy (AUC=0.979 and 0.986 respectively) and was correlated with amyloid PET centiloid and CSF Aβ42/Aβ40 (Spearman R=0.73 and ‐0.76, p&lt;0.0001). Notably, the correlation between pT217/T217 and amyloid PET centiloid was higher in amyloid PET(+)/tau PET(‐) compared to amyloid PET(+)/tau‐PET(+) (R=0.77, p&lt;0.0001 versus 0.16, p=0.007). PT205/T205 and pT217/T217 better predicted tau PET positivity in amyloid PET(+)positive participants (AUC=0.908 and 0.866). These markers were also associated with tau PET signal in tau PET(+) participants (R=0.53 and 0.55 p&lt;0.0001). Other p‐tau isoforms also predicted amyloidosis, except for T175, S199, S202 and T205. Only pT205/T205 and pT217/T217 were correlated with tau‐PET in tau PET(+) participants.ConclusionThese results suggest that tau hyperphosphorylation, notably at T217, is more strongly associated with brain amyloid burden than tau deposition in tau PET(‐) individuals. After tau PET becomes positive, p‐tau217 and p‐tau205 are correlated with tau burden. Soluble p‐tau are markers of both amyloid and tau aggregation in the AD brain.

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-β 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+ (β = −0.056 ± 0.005, T = −11.55, P < 0.001), A+TMTL+ (β = −0.024 ± 0.005, T = −4.72, P < 0.001) and A+T− (β = −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.

The Calcium Score's power of zero in 82-Rubidium PET depending on age group and sex

Abstract Background Coronary calcium score (CAC) is a well-validated method to detect coronary artery disease (CAD). A significant number of patients referred for functional ischaemia tests reveal a normal result. CAC could be a potential gatekeeper to reduce unnecessary testing. Purpose Study aims were to describe the frequency of zero calcium and its diagnostic power to exclude abnormal perfusion stratified by age and sex in a large cohort undergoing 82-Rubidium Positron Emission Tomography (PET). Methods All consecutive patients with suspected CAD who were referred for myocardial perfusion PET at our tertiary center between 2016 and 2021 were identified. Baseline and scan related data were extracted from the electronic database. Patients were included for this retrospective analysis if CAC and semi-quantitative analysis of perfusion study were available. Percentiles and test characteristics of zero calcium were calculated stratified by age and sex. Summed stress score (SSS) ≥4 on PET was considered abnormal. Results 2640 patients were included. Mean age was 65±11 years; 54% were male. Angina and dyspnea were present in 39% and 60%, respectively. 21% (558/2640) of the scans were abnormal and median CAC was 62 [0–374]. 685 patients (26%) had no calcium. Stratified by age, the proportion of zero calcium was 89% (&amp;lt;40 years), 61% (40–49y), 40% (50–59y), 21% (60–69y), 14% (70–79y) and 6% (≥80y). CAC was higher in abnormal scans (median 561 vs. 27, p&amp;lt;0.001) and zero CAC was associated with a lower risk of abnormal PET (2.6% vs. 27.6%, p&amp;lt;0.001). The negative predictive value (NPV) of calcium zero to exclude abnormal PET was 97%, 96% and 98% for all patients, males and females, respectively. Test characteristics are displayed in Table 1. Percentiles of CAC according to scan result are depicted in Figure 1. Conclusion The proportion of zero calcium is frequent and declines with increasing age. The absence of coronary calcium is associated with less abnormal PET scans. Zero calcium to exclude an abnormal scan performed best in young patients (&amp;lt;50) with a NPV ≥98%. CAC could act as a gatekeeper. However, further studies including safety endpoints are needed. The upper calcium score indicates the 90th percentile of patients with normal PET. The lower calcium score indicates the 5th percentile of patients with abnormal PET. Calcium scores within the white area are unlikely to be associated with abnormal PET (since this area includes only the 5% of abnormal PET scans). The dark grey area indicates patients with a high likelihood of positive PET. For better readability, different scales were used. Funding Acknowledgement Type of funding sources: None.

The use of lipid-lowering medication after diagnostic imaging procedures in patients with chest pain

Abstract Background Coronary CT angiography (CTA) combined with myocardial perfusion imaging accurately detects both non-obstructive and obstructive coronary artery disease (CAD). Lipid-lowering therapy is known to effectively reduce cardiovascular events, but the impact of non-invasive imaging findings on the usage of lipid-lowering therapy remains largely unknown. Purpose To assess the use of lipid-lowering medication in patients referred to coronary CTA and subsequent positron emission tomography (PET) myocardial perfusion imaging due to suspected obstructive CAD. Methods We retrospectively analyzed data on purchases of lipid-lowering drugs obtained from the Finnish national registry for a time period starting 1 year before and ending 2 years after the date of diagnostic imaging. This time period was divided into six 6-month intervals, for each of which the presence of any statin and/or ezetimibe purchase was recorded. According to the local routine, patients with suspected obstructive (≥50%) stenosis on coronary CTA entered downstream 15O-water PET myocardial perfusion imaging during adenosine stress to assess the hemodynamic significance of the coronary stenosis. The use of medication was compared among patients with normal coronary arteries, non-obstructive CAD, and obstructive CAD. Results During 2008–2016, a total of 1973 patients (41% male, median age 63 years) underwent coronary CTA and 33% of these had PET perfusion imaging. There were 9081 purchases of lipid-lowering drugs during the 3-year observation period. There were 676 (34%) patients with normal coronary arteries, 640 (32%) patients with non-obstructive atherosclerosis on CTA, 325 (16%) patients with suspected obstructive stenosis on CTA but normal PET perfusion, and 332 (17%) patients with obstructive stenosis and abnormal hyperemic PET perfusion. The proportion of patients buying lipid-lowering drugs was 24%, 51%, 72%, and 91%, respectively, as assessed within the 6-month interval following the CTA/PET imaging. After diagnostic testing, proportion of patients purchasing lipid-lowering medications increased in all groups except those with normal coronary arteries (Figure 1). However, there was a marked decrease in all patient groups in proportion of patients using lipid-lowering medication towards the end of the 2-year follow-up period. Conclusions In a real-world cohort of symptomatic patients with chest pain undergoing diagnostic imaging for suspected CAD, subsequent purchases of lipid-lowering drugs increase in relation to the severity of imaging findings. Although majority of patients with obstructive CAD initially purchased lipid-lowering medication, our results indicate a marked decrease in the use of these preventive medications towards the end of 2-year follow-up period. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): State Research Funding of Turku University Hospital; the Academy of Finland; Finnish Foundation for Cardiovascular Research.

Cardiac Metastasis of Neuroendocrine Tumor Without Cardiovascular Symptoms

A 72-year-old man with a stage IV small intestinal neuroendocrine tumor presented to our cardiology clinic as a referral for an abnormal positron emission tomography–computed tomography scan with an intense gallium uptake in the heart. Follow-up cardiac magnetic resonance was suggestive of myocardium infiltration by the neuroendocrine tumor with late gadolinium enhancement and T1 time elevation. (Level of Difficulty: Intermediate.)

Left ventricular ejection fraction, myocardial blood flow and hemodynamic variables in adenosine and regadenoson vasodilator 82-Rubidium PET

AimsIn most Rubidium-(Rb)-positron emission tomography (PET) studies, dipyridamole was used as vasodilator. The aim was to evaluate vasodilator PET left ventricular ejection fraction (LVEF), myocardial blood flow (MBF), hemodynamics, and the influence of adenosine and regadenoson on these variables. Methods and resultsConsecutive patients (N = 2299) with prior coronary artery disease (CAD) or no prior CAD undergoing adenosine/regadenoson 82Rb-PET were studied and compared according to CAD status and normal/abnormal PET (summed stress score 0-3 vs. ≥4). Rest and stress LVEF differed significantly depending on CAD status and scan results. In patients with no prior CAD, rest/stress LVEF were 68% and 72%, in patients with prior CAD 60% and 63%. LVEF during stress increased 5 ± 6% in normal compared to 1 ± 8% in abnormal PET (P<0.001). Global rest myocardial blood flow(rMBF), stress MBF(sMBF) and myocardial flow reserve (sMBF/rMBF) were significantly higher in no prior CAD patients compared to prior CAD patients(1.3 ± 0.5, 3.3 ± 0.9, 2.6 ± 0.8 and 1.2 ± 0.4, 2.6 ± 0.8, 2.4 ± 0.8 ml/g/min, respectively, P<0.001) and in normal versus abnormal scans, irrespective of CAD status(no prior CAD: 1.4 ± 0.5, 3.5 ± 0.8, 2.8 ± 0.8 and 1.2 ± 0.8, 2.5 ± 0.8, 2.2 ± 0.7; prior CAD: 1.3 ± 0.4, 3.1 ± 0.8, 2.7 ± 0.8 and 1.1 ± 0.4, 2.3 ± 0.7, 2.2 ± 0.7 ml/g/min, respectively, P<0.001). LVEF and hemodynamic values were similar for adenosine and regadenoson stress. Stress LVEF ≥70% excluded relevant ischemia (≥10%) with a negative predictive value (NPV) of 94% (CI 92-95%). ConclusionsRest/stress LVEF, LVEF reserve and MBF values are lower in abnormal compared to normal scans. Adenosine and regadenoson seem to have similar effect on stress LVEF, MBF and hemodynamics. A stress LVEF ≥70% has a high NPV to exclude relevant ischemia.

PET Scan for CAV Screening in Heart Transplant Patients: A Real World Experience

<h3>Purpose</h3> Cardiac allograft vasculopathy (CAV) is a major cause of late morbidity and mortality after heart transplantation (HT). Positron emission tomography (PET) has emerged as a non-invasive screening modality, associated with invasive hemodynamic flow indices and outcomes in several small-scale studies. Our aim was to assess the real-world performance of 13N-Ammonia PET scan (PET) for the development of CAV. <h3>Methods</h3> Single center retrospective analysis of all HT patients who had an angiogram within one year before and after PET scan for CAV screening. CAV was defined as International Society of Heart and Lung Transplantation CAV_1-3. PET indices indicative of CAV were defined as any of: myocardial flow reserve (MFR) < 2.9, stress blood flow (SBF) < 2.3, or coronary vascular resistance (CVR) > 55. <h3>Results</h3> A total of 112 patients met study criteria, 13 were excluded for having CAV on pre-PET angiogram. Of the remaining 99 patients, Mean age was 52±14, 67 (68%) were males, 28 (28%) had ischemic cardiomyopathy, 35 (35%) had diabetes and 26 (26%) were hypertensive. PET was abnormal in 53 pts (54%). Repeat LHC demonstrated new CAV in 9 of these, all of whom had non-obstructive coronary artery disease (NCAD) on LHC. Overall PET had a 100% sensitivity and 51% specificity for identifying CAV. Two or more abnormal PET parameters showed 78% specificity (67% sensitivity) for the prediction of CAV. <h3>Conclusion</h3> Implementing a strategy of 13N-Ammonia PET scan performed a year after a negative LHC for CAV screening, resulted in excellent sensitivity but low specificity. Epicardial CAV was strongly associated with microvascular dysfunction evident by increased CVR and NCAD. Optimal PET thresholds for CAV screening need further refinement.

Calcified versus non-calcified plaque volume fraction in patients with coronary artery disease and their association with outcome

Abstract Background The amount of coronary artery calcification is a general marker of coronary atherosclerosis and has been associated with increased risk of adverse cardiac events. On the other hand, calcification of coronary artery plaques has also been considered as a marker of plaque stabilization. Purpose We hypothesized that the fraction of the non-calcified volume of the total plaque volume in patients with coronary artery disease (CAD) is associated with abnormal myocardial perfusion and increased risk of future cardiac events. Methods Consecutive patients with suspected CAD undergoing sequential coronary computed tomography angiography (CCTA) with selective positron emission tomography (PET) perfusion imaging between 2007 and 2011 were selected. The total, calcified and non-calcified plaque volume (PV) were defined at patient-level. The non-calcified plaque volume fraction was calculated by dividing the non-calcified PV by the total PV, and expressed as percentage. Patients were divided into three groups: patients with 1) non-obstructive CAD (&amp;lt;50% diameter stenosis), 2) suspected coronary stenosis but normal PET perfusion and 3) suspected stenosis and abnormal regional PET perfusion. Difference between high vs. low PV was based on the median value. Clinical outcomes including all-cause mortality and myocardial infarction were recorded for 6.1 [SD 5.3–7.5] years. Results In total, 494 patients (age 63±9 years, 55% male) with documented atherosclerosis on CCTA were included. Total PV, calcified PV and non-calcified PV were all significantly larger in patients with abnormal myocardial perfusion compared to patients with non-obstructive CAD (370 [197–739] mm3 vs. 108 [59–177] mm3, 84 [23–220] mm3 vs. 9 [1–34] mm3 and 274 [157–500] mm3 vs. 94 [53–140] mm3, respectively, p&amp;lt;0.001 for all). However, the non-calcified fraction was smaller in patients with reduced myocardial perfusion (75 [63–86]% vs. 89 [76–98]%, p&amp;lt;0.001, Figure 1). During follow-up 35 events occurred. Patients with higher total PV, calcified PV and non-calcified PV showed worse outcome compared to patients with lower PV (log-rank p&amp;lt;0.001, Figure 2). In contrast, patients with a lower non-calcified plaque volume fraction showed poorer outcome (log-rank χ2=5.54; p=0.019) even after adjusting for statin therapy or revascularization. Conclusion We observed that higher volumes of any plaque component in general are associated with abnormal perfusion and increased risk of future cardiac events. In contrast, patients with a lower non-calcified plaque volume fraction showed poorer outcome. Funding Acknowledgement Type of funding sources: None. Non-calcified plaque volume fractionKaplan-Meier survival analysis