Comparison of Plasma Input and Reference Tissue Models for Analysing [¹¹C]flumazenil Studies

Abstract

A single-tissue compartment model with plasma input is the established method for analysing [ 11 C]flumazenil ([ 11 C]FMZ) studies. However, arterial cannulation and measurement of metabolites are time-consuming. Therefore, a reference tissue approach is appealing, but this approach has not been fully validated for [11 C]FMZ. Dynamic [ 11 C]FMZ positron emission tomography scans with arterial blood sampling were performed in nine drug-free depressive patients and eight healthy subjects. Regions of interest were defined on co-registered magnetic resonance imaging scans and projected onto dynamic [11 C]FMZ images. Using a Hill-type metabolite function, single (1T) and reversible two-tissue (2T) compartmental models were compared. Simplified reference tissue model (SRTM) and full reference tissue model (FRTM) were investigated using both pons and (centrum semiovale) white matter as reference tissue. The 2T model provided the best fit in 59% of cases. Two-tissue V T values were on average 1.6% higher than 1T V T values. Owing to the higher rejection rate of 2T fits (7.3%), the 1T model was selected as plasma input method of choice. SRTM was superior to FRTM, irrespective whether pons or white matter was used as reference tissue. BP ND values obtained with SRTM correlated strongly with 1T V T (r = 0.998 and 0.995 for pons and white matter, respectively). Use of white matter as reference tissue resulted in 5.5% rejected fits, primarily in areas with intermediate receptor density. No fits were rejected using pons as reference tissue. Pons produced 23% higher BP ND values than white matter. In conclusion, for most clinical studies, SRTM with pons as reference tissue can be used for quantifying [ 11 C]FMZ binding.

Validation of reference tissue modelling for [11C]flumazenil positron emission tomography following head injury

“…Consequently, the findings of this study may not be relevant for reference tissue modelling of scans conducted within a few days of the injury. V T of the pons was not significantly different for the two groups, and the control group values are in close agreement with those of Klumpers et al [20]. The lack of difference in pons V T provides further evidence that the pons remains a valid reference region following head injury.…”

“…Although it has been reported that there is some specific binding in pons [31], the use of the pons as a reference tissue for [ 11 C]FMZ has been validated in controls [6,[18][19][20][21][22] and other neuronal conditions [20,21]. Head injury is known to result in damage across the brain, even in regions which appear structurally normal [7,32].…”

“…Following review of MR data to exclude evidence of injury, the pons region of interest (ROI) was drawn using Analyze 7.0 (Biomedical Imaging Resource, Mayo Clinic, Rochester, MN, USA) on 10 contiguous transverse planes of the re-orientated SPGR MR, as previously described [20]. In addition, for each patient, a peri-lesional ROI was created.…”

“…The pons has been used as a reference tissue for [ 11 C]FMZ and is validated for control subjects [6,[18][19][20][21][22] and various neurological disease patients [20,21].…”

Tobacco smoking interferes with GABA A receptor neuroadaptations during prolonged alcohol withdrawal

“…Data were reconstructed and analyzed as previously described (39), with one exception. Specifically, binding potential (BP ND ) was calculated using the simplified reference tissue model (40,41), with pons as the reference region (41). The following ROIs were delineated on the parametric BP ND image: frontal cortex, occipital cortex, temporal cortex, and cerebellum.…”