Noninvasive Quantification of Myocardial ¹¹C-Meta-Hydroxyephedrine Kinetics

Abstract

11 C-meta-hydroxyephedrine ( 11 C-HED) kinetics in the myocardium can be quantified using a single-tissue-compartment model together with a metabolite-corrected arterial blood sampler input function (BSIF). The need for arterial blood sampling, however, limits clinical applicability. The purpose of this study was to investigate the feasibility of replacing arterial sampling with imaging-derived input function (IDIF) and venous blood samples. Methods: Twenty patients underwent 60-min dynamic 11 C-HED PET/CT scans with online arterial blood sampling. Thirteen of these patients also underwent venous blood sampling. Data were reconstructed using both 3-dimensional row-action maximum-likelihood algorithm (3DR) and a time-of-flight (TF) list-mode reconstruction algorithm. For each reconstruction, IDIF results were compared with BSIF results. In addition, IDIF results obtained with venous blood samples and with a transformed venous-to-arterial metabolite correction were compared with results obtained with arterial metabolite corrections. Results: Correlations between IDIF-and BSIF-derived K 1 and V T were high (r 2 . 50.89 for 3DR and TF). Slopes of the linear fits were significantly different from 1 for K 1 , for both 3DR (slope 5 0.94) and TF (slope 5 1.06). For V T , the slope of the linear fit was different from 1 for TF (slope 5 0.93) but not for 3DR (slope 5 0.98). Use of venous blood data introduced a large bias in V T (r 2 5 0.96, slope 5 0.84) and a small bias in K 1 (r 2 5 0.99, slope 5 0.98). Use of a second-order polynomial venous-to-arterial transformation was robust and greatly reduced bias in V T (r 2 5 0.97, slope 5 0.99) with no effect on K 1 . Conclusion: IDIF yielded precise results for both 3DR and TF. Venous blood samples can be used for absolute quantification of 11 C-HED studies, provided a venous-to-arterial transformation is applied. A venous-to-arterial transformation enables noninvasive, absolute quantification of 11 C-HED studies.

[11C]mHED PET follows a two-tissue compartment model in mouse myocardium with norepinephrine transporter (NET)-dependent uptake, while [18F]LMI1195 uptake is NET-independent

“…In humans, [ 11 C]mHED uptake is stronger affected by myocardial blood flow than in mice (under isoflurane anaesthesia), as the mean human resting myocardial blood flow is ~ 1 ml/min/g [ 29 ] (0.5–0.6 ml/min/g plasma flow), while K 1 of [ 11 C]mHED uptake was up to 0.6 ml/min/g in a recent PET study [ 30 ]. Patients with ongoing ischemia may display regionally reduced [ 11 C]mHED uptake due to significant perfusion defects [ 31 ].…”

Bisoprolol therapy does not reduce right ventricular sympathetic activity in pulmonary arterial hypertension patients

“…Ratios of plasma/whole blood concentrations and parent fractions derived from the manual blood samples were fitted to a sigmoid function after a venous-to-arterial blood transformation was applied. 19 Subsequently, the arterial whole blood TAC was multiplied by both the fitted plasma/whole blood ratio and parent fraction curves to obtain the metabolite corrected arterial plasma TAC. Next, segmental VOIs were defined manually in all short axis images of the final frame of the dynamic scan.…”

Reproducible Quantification of Regional Sympathetic Denervation with [11C]meta-Hydroxyephedrine PET Imaging

“…In the literature, other parameters have been assessed using HED PET such as the global LV mean retention index and volumes of distribution. [15,25] These have been shown to be more susceptible to variation than the regional denervation scores, using either the retention index model or the distribution volume model. [15] These studies have concluded that the largest sources of variation were factors related to test-retest variability, rather than variability between observers.…”