Long-term prognostic value of [15O]H2O PET imaging in patients suspected for cerebral hemodynamic insufficiency.

OBJECTIVES: Quantitative regional cerebral perfusion (rCBF) measurements using [15O]H2O PET with arterial cannulation and acetazolamide (ACZ) challenge have been reserved to identify high-risk patients that are candidates for by-pass operation. We aimed to assess the prognostic value of various parameters in quantitative [15O]H2O PET measurements in patients not subsequently undergoing surgery. METHODS: We identified 32 eligible patients who underwent [15O]H2O brain PET imaging for suspicion of hemodynamic insufficiency between 2009 and 2020. Cerebrovascular events were defined as new ischemic lesions on MRI, stroke, transient ischemic attack, vascular dementia. Follow-up period was 91 months (range: 26-146). rCBF before (rCBFbase) and after (rCBFacz) ACZ challenge and the relative increase (CVR), were examined in the anterior (ACA), middle (MCA), and posterior (PCA) cerebral artery territories of the affected hemisphere, and the most recent MRI scans were scored for infarcts and white matter lesions. RESULTS: Receiver operating characteristic (ROC) curve analysis showed higher prognostic accuracy for rCBFacz(AUC:0.82) compared to CVR (AUC:0.72) and rCBFbase (AUC:0.77). ROC AUC, optimal thresholds (and corresponding sensitivity/specificity/accuracy) for rCBFacz after ACZ in individual territories were 0.79 and 37.8 mL 100g-1 min-1 (0.81/0.63/0.72) for the ACA, 0.84 and 32 mL 100g-1 min-1 (0.81/0.75/0.78) for the MCA, and 0.70 and 43.9 ml/(mL 100g-1 min-1 (0.81/0.43/0,62) for the PCA. Kaplan Meier survival curve showed longer event-free survival in patients with rCBFacz below cut-off (p=0.007). In multivariate analysis rCBFacz remained a significant predictor when correcting for age. CONCLUSION: Quantitative rCBF measurements after ACZ challenge with [15O]H2O PET provided high prognostic value for future cerebrovascular events.

82Rb and [15O]H2O myocardial perfusion PET imaging: a prospective head to head comparison.

BACKGROUND: 82Rb PET and [15O]H2O PET are both validated tracers for myocardical perfusion imaging but have not previously been compared clinically. During our site's transition from 82Rb to [15O]H2O PET, we performed a head-to-head comparison in a mixed population with suspected ischemic heart disease. METHODS: A total of 37 patients referred for perfusion imaging due to suspicion of coronary stenosis were examined with both 82Rb and [15O]H2O PET on the same day in rest and during adenosine-induced stress. The exams were rated by two blinded readers as normal, regional ischemia, globally reduced myocardial perfusion, or myocardial scarring. For [15O]H2O PET, regional ischemia was defined as two neighboring segments with average stress perfusion ≤ 2.3 mL/(min·g). Further, we evaluated a total perfusion deficit (TPD) of ≥ 10% as a more conservative marker of ischemia. RESULTS: [15O]H2O PET identified more patients with regional ischemia: 17(46%) vs 9(24%), agreement: 59% corresponding to a Cohen's kappa of .31 [95%CI .08-.53], (P < .001). Using the more conservative TPD ≥ 10%, the agreement increased to 86% corresponding to a kappa of .62 [95%CI .33-.92], (P = .001). For the subgroup of patients with no known heart disease (n = 18), the agreement was 94%. Interrater agreement was 95% corresponding to a kappa of .89 [95%CI .74-1.00] (P < .001). CONCLUSIONS: In clinical transition from 82Rb to [15O]H2O PET, it is important to take into account the higher frequency of patients with regional ischemia detected by [15O]H2O PET.

Non-invasive quantification of cerebral glucose metabolism using Gjedde-Patlak plot and image-derived input function from the aorta.

INTRODUCTION: We aimed at evaluating a Gjedde-Patlak plot and non-invasive image-derived input functions (IDIF) from the aorta to quantify cerebral glucose metabolic rate (CMRglc) in comparison to the reference standard based on sampling the arterial input function (AIF). METHOD: Six healthy subjects received 200 MBq [18F]FDG simultaneously with the initiation of a three-part dynamic PET recording consisting of a 15 min-recording of the aorta, a 40 min-recording of the brain and finally 2 min-recording of the aorta. Simultaneously, the arterial 18F concentration was measured via arterial cannulation. Regions of interest were drawn in the aorta and the brain and time-activity curves extracted. The IDIF was obtained by fitting a triple exponential function to the aorta time-activity curve after the initial peak including the late aorta frame, thereby interpolating the arterial blood activity concentration during the brain scan. CMRglc was calculated from Gjedde-Patlak plots using AIF and IDIF, respectively and the predictive value was examined. Results from frontal cortex, insula, hippocampus and cerebellum were compared by paired t-test and agreement between the methods was analyzed by Bland-Altman plot statistics. RESULTS: There was a strong linear relationship and an excellent agreement between the methods (mean±SD of CMRglcIDIF (µmol 100 g-1 min-1), mean difference, mean relative difference, 95% limits of agreement): frontal cortex: 30.8 ± 3.3, 0.5, 2.2%, [-1,6:2.5], insula: 25.4 ± 2.2, 0.4, 2.4%, [-1.4:2.2], hippocampus: 16.9 ± 1.2, 0.4, 3.8%, [-1.1:2.0] and cerebellum: 23.4 ± 1.9, 0.5, 3.1%, [-1.4:2.5]). CONCLUSION: We found excellent agreement between CMRglc obtained with an IDIF from the aorta and the reference standard with AIF. A non-invasive three-part dynamic [18F]FDG PET recording is feasible as a non-invasive alternative for reliable quantification of cerebral glucose metabolism in all scanner systems. This is useful in patients with presumed global cerebral changes owing to systemic disease or for the monitoring of treatment effects.

Diagnostic accuracy of cerebral [18F]FDG PET in atypical parkinsonism.

BACKGROUND: Atypical parkinsonism (AP) often presents with Parkinson's symptoms but has a much worse long-term prognosis. The diagnosis is presently based on clinical criteria, but a cerebral positron emission tomography (PET) scan with [18F]fluoro-2-deoxy-2-D-glucose ([18F]FDG) may assist in the diagnosis of AP such as multiple system atrophy (MSA), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and Lewy body dementia (DLB). Only few studies have evaluated the sensitivity and specificity of [18F]FDG PET for separating the diseases in a mixed patient population, which we aim to assess in a retrospective material. RESULTS: We identified 156 patients referred for a cerebral [18F]FDG PET for suspicion of AP during 2017-2019. The [18F]FDG PET was analysed by a nuclear medicine specialist blinded to clinical information but with access to dopamine transporter imaging. The reference standard was the follow-up clinical diagnosis (follow-up: 6-72 months). The overall accuracy for correct classification was 74%. Classification sensitivity (95% confidence interval, CI) and specificity (95% CI) for MSA (n = 20) were 1.00 (0.83-1.00) and 0.91 (0.85-0.95), for DLB/Parkinson with dementia (PDD) (n = 26) were 0.81 (0.61-0.93) and 0.97 (0.92-0.99) and for CBD/PSP (n = 68) were 0.62 (0.49-0.73) and 0.97 (0.90-0.99). CONCLUSIONS: Our results support the additional use of [18F]FDG PET for the clinical diagnosis of AP with moderate to high sensitivity and specificity. Use of [18F]FDG PET may be beneficial for prognosis and supportive treatment of the patients and useful for future clinical treatment trials.

Cerebral Metabolic Rate of Glucose and Cognitive Tests in Long COVID Patients.

BACKGROUND: Common long-term sequelae after COVID-19 include fatigue and cognitive impairment. Although symptoms interfere with daily living, the underlying pathology is largely unknown. Previous studies report relative hypometabolism in frontal, limbic and cerebellar regions suggesting focal brain involvement. We aimed to determine whether absolute hypometabolism was present and correlated to same day standardized neurocognitive testing. METHODS: Fourteen patients included from a long COVID clinic had cognitive testing and quantitative dynamic [18F]FDG PET of the brain on the same day to correlate cognitive function to metabolic glucose rate. RESULTS: We found no hypometabolism in frontal, limbic and cerebellar regions in cognitively impaired relative to cognitive intact patients. In contrast, the cognitive impaired patients showed higher cerebellar metabolism (p = 0.03), which correlated with more severe deficits in working memory and executive function (p = 0.03). CONCLUSIONS: Hypermetabolism in the cerebellum may reflect inefficient brain processing and play a role in cognitive impairments after COVID-19.

[Limb-shaking transient ischaemic attack].

Limb-shaking transient ischaemic attack (LS-TIA) is a symptom of cerebral haemodynamic failure caused by large vessel disease. LS-TIA often remains unrecognised though associated with a poor prognosis. The patient presents with irregular hemiform jerks caused by ischaemia. Imaging demonstrating reduced perfusion or/and flow is essential for the diagnosis, and treatment is aimed at reducing development in atherosclerosis and improving perfusion. As described in this review, management is focused optimising secondary prevention, and in selected cases surgical interventions are considered. Evidence remains weak, especially as to surgical interventions.