Use of an Automated Quantitative Analysis of Hippocampal Volume, Signal, and Glucose Metabolism to Detect Hippocampal Sclerosis.

Purpose: Magnetic resonance imaging (MRI) and positron emission tomography (PET) with 18F-fluorodeoxyglucose (18FDG) are valuable tools for evaluating hippocampal sclerosis (HS); however, bias may arise during visual analyses. The aim of this study was to evaluate and compare MRI and PET post-processing techniques, automated quantitative hippocampal volume (Q-volume), and fluid-attenuated inversion-recovery (FLAIR) signal (Q-FLAIR) and glucose metabolism (Q-PET) analyses in patients with HS. Methods: We collected MRI and 18FDG-PET images from 54 patients with HS and 22 healthy controls and independently performed conventional visual analyses (CVA) of PET (CVA-PET) and MRI (CVA-MRI) images. During the subsequent quantitative analyses, the hippocampus was segmented from the 3D T1 image, and the mean volumetric, FLAIR intensity and standardized uptake value ratio (SUVR) values of the left and right hippocampus were assessed in each subject. Threshold confidence levels calculated from the mean volumetric, FLAIR intensity and SUVR values of the controls were used to identify healthy subjects or subjects with HS. The performance of the three methods was assessed using receiver operating characteristic (ROC) curves, and the detection rates of CVA-MRI, CVA-PET, Q-volume, Q-FLAIR, and Q-PET were statistically compared. Results: The areas under the curves (AUCs) for the Q-volume, Q-FLAIR, and Q-PET ROC analyses were 0.88, 0.41, and 0.98, which suggested a diagnostic method with moderate, poor, and high accuracy, respectively. Although Q-PET had the highest detection rate among the two CVA methods and three quantitative methods, the difference between Q-volume and Q-PET did not reach statistical significance. Regarding the HS subtypes, CVA-MRI, CVA-PET, Q-volume, and Q-PET had similar detection rates for type 1 HS, and Q-PET was the most sensitive method for detecting types 2 and 3 HS. Conclusions: In MRI or 18FDG-PET images that have been visually assessed by experts, the quantification of hippocampal volume or glucose uptake can increase the detection of HS and appear to be additional valuable diagnostic tools for evaluating patients with epilepsy who are suspected of having HS.

Multimodality Image Post-processing in Detection of Extratemporal MRI-Negative Cortical Dysplasia.

Purpose: To determine the diagnostic value of individual image post-processing techniques in a series of patients who underwent extratemporal operations for histologically proven, MRI-negative focal cortical dysplasia (FCD). Methods: The morphometric analysis program (MAP), PET/MRI co-registration and statistical parametric mapping (SPM) analysis of PET (SPM-PET) techniques were analyzed in 33 consecutive patients. The epileptogenic zone (EZ) assumed by MAP, PET/MRI, and SPM-PET was compared with the location of the FCD lesions determined by stereoelectroencephalography (SEEG) and histopathological study. The detection rate of each modality was statistically compared. Results: Three lesions were simultaneously detected by the three post-processing methods, while two lesions were only MAP positive, and 8 were only PET/MRI positive. The detection rate of MAP, PET/MRI, SPM-PET and the combination of the three modalities was 24.2, 90.9, 57.6, and 97.0%, respectively. Taking the pathological subtype into account, no type I lesions were detected by MAP, and PET/MRI was the most sensitive method for detecting FCD types II and IIA. During a mean follow-up period of 22.94 months, seizure freedom was attained in 26/33 patients (78.8%) after focal corticectomy. Conclusions: MAP, PET/MRI, and SPM-PET provide complementary information for FCD detection, intracranial electrode design, and lesion resection. PET/MRI was particularly useful, with the highest detection rate of extratemporal MRI-negative FCD.

Ultrahigh-Magnitude Brain Magnetic Resonance Imaging Scan on Rhesus Monkeys With Implanted Deep Brain Stimulation Hardware.

BACKGROUND: Patients with implanted deep brain stimulation (DBS) hardware are prohibited from undergoing magnetic resonance imaging (MRI) scans at magnitudes greater than 1.5 T to avoid potential MRI-related heating injury. Whether DBS devices are compatible with higher field MRI scanning is unknown. This study aimed to investigate whether 7.0 T and 3.0 T MRI scans can be safely performed on rhesus monkeys with implanted DBS devices. METHODS: Eight male rhesus monkeys were included in this study and stereotactically implanted with DBS devices in the left anterior thalamus. Two weeks after DBS device implantation, 7.0 T and 3.0 T MRI scans were performed. The monkeys were observed for 72 hours. After explantation of the DBS system, 7.0 T MRI was repeated to determine potential lesions. Hematoxylin and eosin staining and transmission electron microscopy were conducted to assess pathological alterations. RESULTS: In both groups, the monkeys exhibited no behavioral changes related to neurological deficits. Post-explantation MRI showed no malacia foci surrounding the DBS tracks. Additionally, neither hematoxylin and eosin staining nor transmission electron microscopy showed clear injury near the DBS leads. CONCLUSION: These results indicate that no obvious heating injury was induced in the tissue surrounding the DBS leads by the 7.0 T and 3.0 T MRI scans. Although the results of this study may not be generalizable, these data suggest that patients with implanted DBS devices can undergo even 7.0 T MRI without risk of brain injury.

An oriental melon 9-lipoxygenase gene CmLOX09 response to stresses, hormones, and signal substances / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

In plants, lipoxygenases (LOXs) play a crucial role in biotic and abiotic stresses. In our previous study, five 13-LOX genes of oriental melon were regulated by abiotic stress but it is unclear whether the 9-LOX is involved in biotic and abiotic stresses. The promoter analysis revealed that CmLOX09 (type of 9-LOX) has hormone elements, signal substances, and stress elements. We analyzed the expression of CmLOX09 and its downstream genes-CmHPL and CmAOS-in the leaves of four-leaf stage seedlings of the oriental melon cultivar "Yumeiren" under wound, hormone, and signal substances. CmLOX09, CmHPL, and CmAOS were all induced by wounding. CmLOX09 was induced by auxin (indole acetic acid, IAA) and gibberellins (GA3); however, CmHPL and CmAOS showed differential responses to IAA and GA3. CmLOX09, CmHPL, and CmAOS were all induced by hydrogen peroxide (H2O2) and methyl jasmonate (MeJA), while being inhibited by abscisic acid (ABA) and salicylic acid (SA). CmLOX09, CmHPL, and CmAOS were all induced by the powdery mildew pathogen Podosphaera xanthii. The content of 2-hexynol and 2-hexenal in leaves after MeJA treatment was significantly higher than that in the control. After infection with P. xanthii, the diseased leaves of the oriental melon were divided into four levels-levels 1, 2, 3, and 4. The content of jasmonic acid (JA) in the leaves of levels 1 and 3 was significantly higher than that in the level 0 leaves. In summary, the results suggested that CmLOX09 might play a positive role in the response to MeJA through the hydroperoxide lyase (HPL) pathway to produce C6 alcohols and aldehydes, and in the response to P. xanthii through the allene oxide synthase (AOS) pathway to form JA.

Ultra-high magnetic resonance imaging (MRI): a potential examination for deep brain stimulation devices and the limitation study concerning MRI-related heating injury.

Nowadays, the patients with deep brain stimulation (DBS) devices are restricted to undertake 1.5T magnetic resonance imaging (MRI) according to the guideline. Nevertheless, we conducted an experiment to test pathological change near the leads in different field-strength MRI. Twenty-four male New Zealand rabbits were assigned to Group 1 (G1, n = 6, 7.0T, DBS), Group 2 (G2, n = 6, 3.0T, DBS), Group 3 (G3, n = 6, 1.5T, DBS), and Group 4 (G4, n = 6, 1.5T, paracentesis). DBS leads were implanted in G1, G2 and G3, targeting left nucleus ventralis posterior thalami. Paracentesis was performed in G4. 24 h after MRI scan, all animals were killed for examining pathological alternation (at different distance from lead) via transmission electron microscopy. Our results suggest that the severity of tissue injury correlates with the distance to electrode instead of field strength of MRI. Up to now, the reason for the restriction of MRI indicated no significantly different pathological change.

Potential Protective Effects of Chronic Anterior Thalamic Nucleus Stimulation on Hippocampal Neurons in Epileptic Monkeys.

BACKGROUND: Stimulation of the anterior nucleus of the thalamus (ANT) is effective in seizure reduction, but the mechanisms underlying the beneficial effects of ANT stimulation are unclear. OBJECTIVE: To assess the beneficial effects of ANT stimulation on hippocampal neurons of epileptic monkeys. METHODS: Chronic ANT stimulation was applied to kainic acid-induced epileptic monkeys. Behavioral seizures were continuously monitored. Immunohistochemical staining and western blot assays were performed to assess the hippocampal injury and the effects of ANT stimulation. RESULTS: The frequency of seizures was 42.8% lower in the stimulation group compared with the sham-stimulation group. Immunohistochemical staining and western blot analyses indicated that neuronal loss and apoptosis were less severe and that neurofilament synthesis was enhanced in the stimulation monkeys compared with the sham-stimulation group. These data showed that the hippocampal injury was less severe in monkeys in the stimulation group than in those in the sham-stimulation group. CONCLUSIONS: Our data suggest that chronic ANT stimulation may exert protective effects on hippocampal neurons and boost the regeneration of neuronal fibers. These effects may be closely related to the mechanisms of ANT stimulation in epilepsy treatment.

Favorable modulation in neurotransmitters: effects of chronic anterior thalamic nuclei stimulation observed in epileptic monkeys.

Anterior thalamic nuclei (ATN) stimulation has been shown to be effective in seizure reduction. Nevertheless, the underlying mechanisms remain unclear. This study investigated the changes in the amino acid levels during chronic, single-sided ATN-stimulation in the hippocampi of rhesus monkeys with mesial temporal lobe epilepsy induced by kainic acid (KA). The concentrations of glutamate, γ-aminobutyric acid, aspartate and taurine in the dialysates from bilateral hippocampi were determined at multiple time points using high-performance liquid chromatography. The results showed that after KA administration, the aspartate, γ-aminobutyric acid and taurine levels increased significantly in the sham-stimulation group, although the γ-aminobutyric acid and taurine levels gradually returned to the basal levels in the chronic stage. The glutamate level showed an initial decrease in the acute stage and a subsequent increase in the chronic stage. Chronic ATN-stimulation reversed the increases in the glutamate and aspartate levels, and maintained the initial increases in the γ-aminobutyric acid and taurine levels till the end of the experiment. These amino acid levels, however, were not affected by either contralateral KA injection or contralateral ATN-stimulation, suggesting that the observed effects of ATN-stimulation are restricted to the ipsilateral hemisphere. Our data suggest that chronic ATN-stimulation may induce favorable modulations in the amino acid levels in the hippocampi of epileptic monkeys, which may be an important mechanism underlying the effects of ATN-stimulation in epilepsy treatment.

Pathological alterations and stress responses near DBS electrodes after MRI scans at 7.0T, 3.0T and 1.5T: an in vivo comparative study.

OBJECTIVE: The purpose of this study was to investigate the pathological alterations and the stress responses around deep brain stimulation (DBS) electrodes after magnetic resonance imaging (MRI) scans at 7.0T, 3.0T and 1.5T. MATERIALS AND METHODS: DBS devices were stereotactically implanted into the brains of New Zealand rabbits, targeting the left nucleus ventralis posterior thalami, while on the right side, a puncture passage pointing to the same target was made. MRI scans at 7.0T, 3.0T and 1.5T were performed using transmit/receive head coils. The pathological alterations of the surrounding tissue were evaluated by hematoxylin and eosin staining (H&E staining) and transmission electron microscopy (TEM). The levels of the 70 kDa heat shock protein (HSP-70), Neuronal Nuclei (NeuN) and Caspase-3 were determined by western-blotting and quantitative polymerase chain reaction (QPCR) to assess the stress responses near the DBS electrodes. RESULTS: H&E staining and TEM showed that the injury around the DBS electrodes was featured by a central puncture passage with gradually weakened injurious alterations. Comparisons of the injury across the groups manifested similar pathological alterations near the DBS electrodes in each group. Moreover, western-blotting and QPCR assay showed that the level of HSP-70 was not elevated by MRI scans (p>0.05), and the levels of NeuN and Caspase-3 were equal in each group, regardless of the field strengths applied (p>0.05). CONCLUSIONS: Based on these findings, it is reasonable to conclude that in this study the MRI scans at multiple levels failed to induce additional tissue injury around the DBS electrodes. These preliminary data furthered our understanding of MRI-related DBS heating and encouraged revisions of the current MRI guidelines for patients with DBS devices.

[Expression of peroxisome proliferator-activated receptor-gamma in human pituitary adenomas and its correlation to tumor invasiveness].

BACKGROUND & OBJECTIVE: Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a nuclear transcription factor. Its ligant can inhibit proliferation and enhance differentiation of tumor cells, which plays crucial roles in metastasis and invasion of tumors. This study was to investigate the expression of PPARgamma in human pituitary adenomas and its clinical significance. METHODS: Immunohistochemistry (IHC) was used to investigate the expression of PPARgamma protein in 78 human pituitary adenomas, including 41 invasive and 37 non-invasive cases. The expression levels of PPARgamma mRNA in 33 human pituitary adenomas, including 16 invasive and 17 non-invasive cases, and three normal pituitary tissues obtained from autopsy were confirm by reverse transcription polymerase chain reaction (RT-PCR). The expression of PPARgamma in invasive and non-invasive pituitary adenomas was analyzed by Chi2 test and t test of the fourfold table. RESULTS: The positive rate of PPARgamma protein was significantly higher in invasive pituitary adenomas than in non-invasive ones (68.09% vs. 38.71%,P<0.05). The PPARgamma mRNA level was significantly higher in pituitary adenomas than in normal pituitary tissues (2.99+/-0.18 vs. 1.55+/-0.25, P<0.05), and higher in invasive pituitary adenomas than in non-invasive cases (3.95+/-0.43 vs. 2.40+/-0.24, P<0.01). CONCLUSIONS: PPARgamma is highly expressed in human pituitary adenomas, especially in the invasive ones. PPARgamma may be used as a new target for the treatment of pituitary adenomas.