Motivated by the great potential of deep learning in medical imaging, we propose an iterative positron emission tomography (PET) reconstruction framework using a deep learning-based prior. We utilized the denoising convolutional neural network (DnCNN) method and trained the network using full-dose images as the ground truth and low dose images reconstructed from downsampled data by Poisson thinning as input. Since most published deep networks are trained at a predetermined noise level, the noise level disparity of training and testing data is a major problem for their applicability as a generalized prior. In particular, the noise level significantly changes in each iteration, which can potentially degrade the overall performance of iterative reconstruction. Due to insufficient existing studies, we conducted simulations and evaluated the degradation of performance at various noise conditions. Our findings indicated that DnCNN produces additional bias induced by the disparity of noise levels. To address this issue, we propose a local linear fitting (LLF) function incorporated with the DnCNN prior to improve the image quality by preventing unwanted bias. We demonstrate that the resultant method is robust against noise level disparities despite the network being trained at a predetermined noise level. By means of bias and standard deviation studies via both simulations and clinical experiments, we show that the proposed method outperforms conventional methods based on total variation (TV) and non-local means (NLM) penalties. We thereby confirm that the proposed method improves the reconstruction result both quantitatively and qualitatively.

Accurate and rapid blood-based detection of dopamine levels can aid in the diagnosis and monitoring of diseases related to dopaminergic dysfunction. For the sensitive detection of dopamine levels in human blood plasma (i.e., plasma dopamine levels), a silver-plated Au bimetallic nanocluster (so called plasmonic Au/Ag nanocluster) was prepared as a surface-enhanced Raman scattering (SERS) substrate by the combination of electrodeposition and electroless plating methods. The plasmonic effect of the Au/Ag nanocluster substrate was optimized by controlling the particle morphology, packing density, and interparticle distance, showing the best performance in its SERS activity. The lowest detection limit of dopamine was ∼10⁻¹¹ M. A linear standard curve was obtained by plotting the log-scale of dopamine concentration (log C) versus Raman intensity at 1152 cm⁻¹. The optimized SERS substrate quantified the plasma dopamine levels of patients with antipsychotic drug-induced Parkinsonism (n = 15) as 3.24 × 10⁻⁹ M and healthy control subjects (n = 15) as 2.31 × 10⁻⁸ M. Patients with drug-induced Parkinsonism had ∼86% lower plasma dopamine concentration than healthy subjects (two-tailed p-value = 0.000002), indicating a clear separation between the groups. Our study provides the first report on the quantitative SERS detection of dopamine levels in human blood plasma with Parkinsonism. The results highlight the potential clinical utility of the optimized SERS technique in screening clinical populations with dopaminergic dysfunction, i.e., differentiating between healthy subjects and patients with Parkinsonism.

Objective: Human impulsivity is a complex multidimensional construct encompassing cognitive, emotional, and behavioural aspects. Previous animal studies have suggested that striatal dopamine receptors play a critical role in impulsivity. In this study, we investigated the relationship between self-reported impulsiveness and dopamine D_2/3 receptor availability in striatal subdivisions in healthy subjects using high-resolution positron emission tomography (PET) with [¹¹C]raclopride.Methods: Twenty-one participants completed 3-T magnetic resonance imaging and high-resolution PET scans with [¹¹C]raclopride. The trait of impulsiveness was measured using the Barratt Impulsiveness Scale (BIS-11). Partial correlation analysis was performed between BIS-11 scores and D_2/3 receptor availability in striatal subregions, controlling for the confounding effects of temperament characteristics that are conceptually or empirically related to dopamine, which were measured by the Temperament and Character Inventory.Results: The analysis revealed that the non-planning (p = 0.004) and attentional (p = 0.007) impulsiveness subscale scores on the BIS-11 had significant positive correlations with D_2/3 receptor availability in the pre-commissural dorsal caudate. There was a tendency towards positive correlation between non-planning impulsiveness score and D_2/3 receptor availability in the post-commissural caudate.Conclusion: These results suggest that cognitive subtrait of impulsivity is associated with D_2/3 receptor availability in the associative striatum that plays a critical role in cognitive processes involving attention to detail, judgement of alternative outcomes, and inhibitory control.

Molecular imaging with positron emission tomography (PET) and single photon emission computed tomography (SPECT) is a well-established and important in vivo technique to evaluate fundamental biological processes and unravel the role of neurotransmitter receptors in various neuropsychiatric disorders. Specific ligands are available for PET/SPECT studies of dopamine, serotonin, and opiate receptors, but corresponding development of radiotracers for receptors of glutamate, the main excitatory neurotransmitter in mammalian brain, has lagged behind. This state of affairs has persisted despite the central importance of glutamate neurotransmission in brain physiology and in disorders such as stroke, epilepsy, schizophrenia, and neurodegenerative diseases. Recent years have seen extensive efforts to develop useful ligands for molecular imaging of subtypes of the ionotropic (N-methyl-D-aspartate (NMDA), kainate, and AMPA/quisqualate receptors) and metabotropic glutamate receptors (types I, II, and III mGluRs). We now review the state of development of radioligands for glutamate receptor imaging, placing main emphasis on the suitability of available ligands for reliable in vivo applications. We give a brief account of the radiosynthetic approach for selected molecules. In general, with the exception of ligands for the GluN2B subunit of NMDA receptors, there has been little success in developing radiotracers for imaging ionotropic glutamate receptors; failure of ligands for the PCP/MK801 binding site in vivo doubtless relates their dependence on the open, unblocked state of the ion channel. Many AMPA and kainite receptor ligands with good binding properties in vitro have failed to give measurable specific binding in the living brain. This may reflect the challenge of developing brain-penetrating ligands for amino acid receptors, compounded by conformational differences in vivo. The situation is better with respect to mGluR imaging, particularly for the mGluR5 subtype. Several successful PET ligands serve for investigations of mGluRs in conditions such as schizophrenia, depression, substance abuse and aging. Considering the centrality and diversity of glutamatergic signaling in brain function, we have relatively few selective and sensitive tools for molecular imaging of ionotropic and metabotropic glutamate receptors. Further radiopharmaceutical research targeting specific subtypes and subunits of the glutamate receptors may yet open up new investigational vistas with broad applications in basic and clinical research.