[18F]FP-(+)-DTBZ PET study in a lactacystin-treated rat model of Parkinson disease.

OBJECTIVE: Lactacystin has been used to establish rodent models of Parkinson disease (PD), with cerebral α-synuclein inclusions. This study evaluated the uptake of [18F]9-fluoropropyl-(+)-dihydrotetrabenazine ([18F]FP-(+)-DTBZ), a vesicular monoamine transporter type 2 (VMAT2)-targeting radiotracer, through positron emission tomography (PET) in lactacystin-treated rat brains. METHODS: Adult male Sprague-Dawley rats were randomly treated with a single intracranial dose of lactacystin (2 or 5 µg) or saline (served as the sham control) into the left medial forebrain bundle. A 30-min static [18F]FP-(+)-DTBZ brain PET scan was performed following an intravenous [18F]FP-(+)-DTBZ dose (approximately 22 MBq) in each animal at 2 and 3 weeks after lactacystin treatment. Upon completing the last PET scans, the animals were killed, and their brains were dissected for ex vivo autoradiography (ARG) and immunohistochemical (IHC) staining of tyrosine hydroxylase (TH) as well as VMAT2. RESULTS: Both the 2- and 5-µg lactacystin-treated groups exhibited significantly decreased specific [18F]FP-(+)-DTBZ uptake in the ipsilateral striata (I-ST) at 2 weeks (1.51 and 1.16, respectively) and 3 weeks (1.36 and 1.00, respectively) after lactacystin treatment, compared with the uptake in the corresponding contralateral striata (C-ST) (3.48 and 3.08 for the 2- and 5-µg lactacystin-treated groups, respectively, at 2 weeks; 3.36 and 3.11 for the 2- and 5-µg lactacystin-treated groups, respectively, at 3 weeks) and the sham controls (3.34-3.53). Lactacystin-induced decline in I-ST [18F]FP-(+)-DTBZ uptake was also demonstrated through ex vivo ARG, and the corresponding dopaminergic neuron damage was confirmed by the results of TH- and VMAT2-IHC studies. CONCLUSIONS: In this PD model, lactacystin-induced dopaminergic terminal damage in the ipsilateral striatum could be clearly visualized through in vivo [18F]FP-(+)-DTBZ PET imaging. This may serve as a useful approach for evaluating the effectiveness of new treatments for PD.

Total variation-based method for generation of intravoxel incoherent motion parametric images in MRI.

PURPOSE: Total variation (TV) method has been used widely for image restoration and reconstruction. In this work, we propose a TV-based algorithm for parametric image generation in intravoxel incoherent motion (IVIM) diffusion-weighted magnetic resonance imaging (DW-MRI). METHODS: We used simulated and real data to investigate whether the proposed TV-based method can provide reliable parametric images. Parametric images of IVIM parameters including perfusion fraction (PF), diffusion coefficient (D), and pseudo-diffusion coefficient (D*) were estimated using DW-MRI data and TV through fitting the IVIM model. The Levenberg-Marquardt (LM) method, which has often been used in the context of IVIM analysis, was employed as the standard method for comparison of the resulting parametric images. RESULTS: The simulation results show that the proposed method outperforms the LM algorithm in terms of precision, providing a 40-81%, 90-93%, and 68-84% improvement for PF, D and D*, respectively, at signal-to-noise ratio (SNR) of 30. For real data, the proposed method showed an average five-fold, three-fold, and four-fold improvement in the SNR for PF, D and D*, respectively. CONCLUSION: We introduced the use of TV to produce parametric images, and demonstrated that the proposed TV-based method is effective in improving the parametric image quality. Magn Reson Med 78:1383-1391, 2017. © 2016 International Society for Magnetic Resonance in Medicine.