Ischemic stroke is a devastating disease and one of the leading causes of mortality worldwide. Overproduction of reactive oxygen and nitrogen species (RONS) following ischemic insult is known as a key factor in exacerbating brain damage. Thus, RONS scavengers that can block excessive production of RONS have great therapeutic potential. Herein, we propose an efficient treatment strategy in which an artificial nanozyme with multienzyme activity drives neuroprotection against ischemic stroke primarily by scavenging RONS. Specifically, through a facile, Bi 3+ -assisted, template-free synthetic strategy, we developed hollow Prussian blue nanozymes (HPBZs) with multienzyme activity to scavenge RONS in a rat model of ischemic stroke. The comprehensive characteristics of HPBZs against RONS were explored. Apart from attenuating oxidative stress, HPBZs also suppressed apoptosis and counteracted inflammation both in vitro and in vivo, thereby contributing to increased brain tolerance of ischemic injury with minimal side effects. This study provides a proof of concept for a novel class of neuroprotective nanoagents that might be beneficial for treatment of ischemic stroke and other RONS-related disorders.

Major depressive disorder (MDD) is a significant cause of morbidity and mortality worldwide, correlating with genetic susceptibility and environmental risk factors. Molecular, functional, and structural imaging approaches have been increasingly used to detect neurobiological changes, analyze neurochemical correlates, and parse pathophysiological mechanisms underlying MDD. We reviewed recent neuroimaging publications on MDD in terms of molecular, functional, and structural alterations as detected mainly by magnetic resonance imaging (MRI) and positron emission tomography. Altered structure and function of brain regions involved in the cognitive control of affective state have been demonstrated. An abnormal default mode network, as revealed by resting-state functional MRI, is likely associated with aberrant metabolic and serotonergic function revealed by radionuclide imaging. Further multi-modal investigations are essential to clarify the characteristics of the cortical network and serotonergic system associated with behavioral and genetic variations in MDD.

PET with 18 F-FDG has been used for presurgical localization of epileptogenic foci; however, in nonsurgical patients, the correlation between cerebral glucose metabolism and clinical severity has not been fully understood. The aim of this study was to evaluate the glucose metabolic profile using 18 F-FDG PET/CT imaging in patients with epilepsy. Methods: One hundred pediatric epilepsy patients who underwent 18 F-FDG PET/CT, MRI, and electroencephalography examinations were included. Fifteen age-matched controls were also included. 18 F-FDG PET images were analyzed by visual assessment combined with statistical parametric mapping (SPM) analysis. The absolute asymmetry index (jAIj) was calculated in patients with regional abnormal glucose metabolism. Results: Visual assessment combined with SPM analysis of 18 F-FDG PET images detected more patients with abnormal glucose metabolism than visual assessment only. The jAIj significantly positively correlated with seizure frequency (P , 0.01) but negatively correlated with the time since last seizure (P , 0.01) in patients with abnormal glucose metabolism. The only significant contributing variable to the jAIj was the time since last seizure, in patients both with hypometabolism (P 5 0.001) and with hypermetabolism (P 5 0.005). For patients with either hypometabolism (P , 0.01) or hypermetabolism (P 5 0.209), higher jAIj values were found in those with drug resistance than with seizure remission. In the post-1-y follow-up PET studies, a significant change of jAIj (%) was found in patients with clinical improvement compared with those with persistence or progression (P , 0.01). Conclusion: 18 F-FDG PET imaging with visual assessment combined with SPM analysis could provide cerebral glucose metabolic profiles in nonsurgical epilepsy patients. jAIj might be used for evaluation of clinical severity and progress in these patients. Patients with a prolonged period of seizure freedom may have more subtle (or no) metabolic abnormalities on PET. The clinical value of PET might be enhanced by timing the scan closer to clinical seizures.

Posttraumatic stress disorder (PTSD) is an anxiety disorder that occurs after exposure to a traumatic event. This study aimed to investigate the neurobiologic changes before and after exposure-based therapy by PET in a rat model of PTSD. Methods: Serial 18 F-FDG PET imaging studies were performed under the control (tone presentation), fear-conditioning, and extinction retrieval phases. Neuroactivity marker c-Fos protein was used for immunostaining. Results: Increased glucose metabolism was observed in the bilateral amygdala after fearconditioning (P , 0.001) and in the right posterior insular cortex under extinction retrieval (P , 0.001) compared with the control phase. Increased c-Fos expression in the posterior insular cortex under extinction retrieval was positively correlated to the glucose metabolism (P , 0.01). Conclusion: Our results indicated that the amygdala plays a key role in fear memory formation and, most importantly, the insular cortex is related to the retrieval of extinction memory. 18 F-FDG PET may provide a promising in vivo approach for evaluating exposurebased therapy of PTSD. Post traumatic stress disorder (PTSD) is the most costly psychiatric disorder, affecting up to 40% of individuals over lifetime exposure to traumatic events (1,2). Over the past decades, considerable studies have explored how fear memories are encoded in the brain. A neurocircuitry model of PTSD emphasized the importance of the amygdala, as well as its interactions with the ventral/ medial prefrontal cortex (PFC) and hippocampus (3). In accord with this model, initial neuroimaging studies of PTSD provided evidence for exaggerated amygdala responses and attenuated ventral/ medial PFC responses during exposure to reminders of the traumatic event (3). In addition, Pavlovian fear-conditioning studies highlighted the key role of the amygdala in the acquisition and storage of conditioned fear memories (4,5). Electrophysiologic recording and inactivation studies in rats suggest that fear extinction depended on increased neuroactivity in the medial PFC under extinction training (6,7). Furthermore, the amygdala has been found activated during fear acquisition (8) and positively correlated with the severity of PTSD symptoms (9). Failure to recall fear extinction memory is associated with lower activation in the hippocampus and ventral/medial PFC in PTSD patients relative to trauma-exposed healthy subjects (10).Although exposure-based therapy (conceptually based on fear extinction) has been widely used in the treatment of PTSD (1), its underlying mechanism has not been completely elucidated. Because PET has been increasingly used to characterize neural activities, we hypothesized that 18 F-FDG PET could be applied for evaluating cerebral glucose metabolism before and after exposure-based therapy and could provide a potential translational tool for future clinical applications. Thus, the present study aimed to investigate the neurobiologic changes by 18 F-FDG PET in a rat model of PTSD. MATERIALS AND METHODS AnimalsMale Sprague-Da...

BackgroundMajor depressive disorder (MDD) is a common mental disorder worldwide, but now there is a lack of clinically effective assessment and management of MDD. In this study, we used technetium-99 m ethylcysteinate dimer ([99mTc]ECD) SPECT/CT to characterize the regional cerebral blood flow (rCBF) status of MDD patients, and to explore an objective image assessment model of MDD which is non- or minimally-invasive, convenient and accurate in a clinical setting.MethodsThe severity of MDD was assessed by three trained psychiatrists, based on scores obtained from HAMD and HAMA. [99mTc]ECD rCBF SPECT/CT was performed in 20 healthy controls and 74 unipolar MDD patients before receiving the treatment. The CT attenuation-corrected SPECT images data were automatically registered, analyzed simultaneously by 3D-SSP and eZIS.ResultsThe mean score of HAMD and HAMA in the MDD patients was 25.49 ± 6.00, and 23.12 ± 5.83, respectively. There was a positive correlation between two scores. The MDD women had higher HAMD scores than MDD men. The decreased rCBF of MDD patients in frontal lobes (bilateral B11, B47 and right B4, B6, B10, B46), temporal lobe (right B21, B41, B42) and cingulated cortex (bilateral B24, B33), while their increased rCBF in occipital lobe (bilateral B17, B19 and left B18). Additionally, the depression severity was negatively correlated with decreased rCBF in left ventral anterior cingulate cortex B24, and was positively correlated with decreased rCBF in left inferior prefrontal gyrus B47 and increased rCBF in right associative visual cortex B19. The anxiety severity was negatively correlated with decreased rCBF in left subgenual cortex B25.ConclusionsAlthough the mechanism underlying the correlation is not yet fully understood, our findings indicated that the rCBF SPECT/CT may provide an objective assessment for MDD severity. It might be used monitoring therapeutic efficacy in the management of MDD.

Pre-surgical evaluation by co-registration of F-FDG PET and HR-MRI could improve the identification of the epileptogenic onset zone (EOZ), and may further guide the surgical decision-making and improve the outcome of the refractory ETLE with normal conventional MRI; therefore, it should be recommended as a standard procedure for pre-surgical evaluation of these patients.

Positron emission tomography (PET) and magnetic resonance imaging (MRI) are established imaging modalities for the study of neurological disorders, such as epilepsy, dementia, psychiatric disorders and so on. Since these two available modalities vary in imaging principle and physical performance, each technique has its own advantages and disadvantages over the other. To acquire the mutual complementary information and reinforce each other, there is a need for the fusion of PET and MRI. This combined dual-modality (either sequential or simultaneous) could generate preferable soft tissue contrast of brain tissue, flexible acquisition parameters, and minimized exposure to radiation. The most unique superiority of PET/MRI is mainly manifested in MRI-based improvement for the inherent limitations of PET, such as motion artifacts, partial volume effect (PVE) and invasive procedure in quantitative analysis. Head motion during scanning significantly deteriorates the effective resolution of PET image, especially for the dynamic scan with lengthy time. Hybrid PET/MRI device can offer motion correction (MC) for PET data through MRI information acquired simultaneously. Regarding the PVE associated with limited spatial resolution, the process and reconstruction of PET data can be further optimized by using acquired MRI either sequentially or simultaneously. The quantitative analysis of dynamic PET data mainly relies upon an invasive arterial blood sampling procedure to acquire arterial input function (AIF). An image-derived input function (IDIF) method without the need of arterial cannulization, can serve as a potential alternative estimation of AIF. Compared with using PET data only, combining anatomical or functional information from MRI for improving the accuracy in IDIF approach has been demonstrated. Yet, due to the interference and inherent disparity between the two modalities, these methods for optimizing PET image based on MRI still have many technical challenges. This review discussed upon the most recent progress, current challenges and future directions of MRI-driven PET data optimization for neurological applications, with either sequential or simultaneous acquisition approach.

A landmark study from the Institute of Medicine reported that the assessment of cognitive difficulties in children with epilepsy is timely and imperative. Anticonvulsant-induced cognitive impairment could influence the quality of life more than seizure itself in patients. Although the monoaminergic system is involved in the regulation of cognitive process, its role in anticonvulsant-induced cognitive impairment remains unclear. To explore in vivo monoamine receptor binding activity in patients with anticonvulsant-induced cognitive impairment, each patient underwent PET imaging with both monoamine receptor binding agentC--methylspiperone and glucose metabolic agent F-FDG. Tests of intelligence quotient (IQ), including verbal IQ (VIQ), performance IQ (PIQ), and full-scale IQ (FSIQ), were performed in each patient. Compared with the patients with monotherapy, patients with polytherapy had significantly lower VIQ, PIQ, and FSIQ ( < 0.01 in each comparison), as well as significantly lower monoamine receptor activities detected in the caudate nucleus, prefrontal cortex, dorsal anterior cingulate cortex, and amygdale ( < 0.05 in each comparison). However, regarding the glucose metabolism, there was no significant difference found in patients with monotherapy or polytherapy ( > 0.05). Monoamine receptor PET imaging could be a promising in vivo imaging biomarker for mapping anticonvulsant-induced cognitive impairment.