雌激素对PD模型大鼠黑质纹状体通路的保护作用及其机制探讨

目的研究雌激素（Estrogen）对6-羟基多巴（6-OHDA）制备的去卵巢（OVX）帕金森病（PD）模型大鼠黑质纹状体通路的保护作用及其可能机制。方法应用6-OHDA两点注射单侧损毁内侧前脑束（MFB）制备OVXPD模型大鼠,侧脑室给予17-β雌二醇（17-βestradiol,1μg/5μl）,观察大鼠旋转行为、黑质酪氨酸羟化酶（TH）基因表达、黑质铁染色阳性细胞数量和纹状体内多巴胺（DA）及其代谢产物含量的变化。结果雌激素用药组可明显减少阿朴吗啡诱导的PD模型大鼠单侧旋转行为（P〈0.01）。在损毁侧黑质,雌激素用药组TH基因的表达较PD模型组明显增加（P〈0.01）;纹状体DA及其代谢产物亦较PD模型组显著升高（P〈0.01）。黑质铁染色阳性细胞数量较PD模型组明显减少（P〈0.01）。结论雌激素对PD模型大鼠黑质DA能神经元有明显的保护作用,其作用机制可能与降低铁负载有关。     

6-羟基多巴脑内注射建立帕金森病大鼠模型的实验研究

目的 探讨6-羟基多巴脑内注射建立稳定的帕金森病大鼠模型的方法.方法 将6-羟基多巴立体定向注入大鼠右侧前脑内侧束和中脑被盖腹侧区,观察大鼠的行为变化和中脑黑质区的形态学变化.结果 注药后2周,动物经阿扑吗啡诱导即出现向健侧的旋转行为,注射效果稳定.在长达3个月的观察中,动物的旋转行为稳定,无明显的差异.形态学显示,毁损侧的黑质致密部和中脑被盖腰侧区的酪氨酸羟化酶阳性神经元的数量明显减少.结论 通过6-羟基多巴脑内注射的方法可以建立起稳定、有效的帕金森病大鼠模型.     

锰离子增强 MRI 在大鼠视觉中枢核团立体定位中的运用

目的：探索锰离子增强磁共振成像(MEMRI)在大鼠视觉中枢核团立体定位中的价值。方法 SD 大鼠36只,分成3组。A 组(1 6只)使用 MEMRI 定位法;B 组(1 6只)使用传统解剖图谱定位;C 组(4只)使用 A 组所取得的数据定位并穿刺中枢核团。A 组定位方法为提前在单侧眼球内注射氯化锰(MnCL2)水溶液(30 mmol/L×3μL),24 h 后行 MRI 确定对侧上丘、外侧膝状体位置;B 组为根据图谱确定上述核团位置。随后,A、B 2组均经颅骨穿刺视觉核团后,注入3%荧光金溶液1μL,5 d 后处死大鼠并取出视网膜铺片,在荧光显微镜下观察视网膜神经节细胞(RGCs)标记情况。C 组则根据 A 组中取得的定位数据确定核团位置,穿刺并注射 MnCL2溶液(30 mmol/L×0.5μL)1 h 后,使用 MRI 观察强化区域,直接验证 MEMRI 定位数据的可靠性。结果 A 组RGCs 标记成功15只(93.8%),B 组 RGCs 标记成功10只(62.5%)。A 组的成功率高于 B 组(P =0.041,<0.05)。C 组 4只均准确命中核团。结论 MEMRI 在大鼠的视觉中枢核团立体定位中可提高定位准确性。     

6-羟基多巴胺诱发帕金森病大鼠模型的制作和评价

目的 向大鼠中脑黑质区注入6-羟基多巴胺(6-OHDA)建立帕金森病(PD)大鼠模型,并从行为学(ethology)及组织病理、生化角度对该模型进行评价.方法 将6-OHDA立体定向微量注入大鼠右侧中脑黑质(SN)区,观察阿朴吗啡(APO)诱发的大鼠旋转行为及黑质细胞形态学变化,测定脑组织液中儿茶酚胺类物质含量及黑质酪氨酸羟化酶的免疫活性.结果 120只大鼠中经APO诱导后有67只(占55.8%)持续转向健侧(旋转圈数＞7r/min),帕金森病大鼠模型复制成功.PD鼠注射侧黑质区多巴胺能神经元数量较对侧明显减少,体积缩小,结构欠清晰.注射侧脑组织液中多巴胺(DA)、3,4-二羟基苯酸(DOPAC)、高香草酸(HVA)、5-羟色胺(5-HT)含量均低于对侧,注射侧黑质致密部酪氨酸羟化酶(TH)免疫阳性细胞较健侧明显减少.连续观察10个月,PD模型大鼠的异常旋转行为无自发性恢复.结论 用6-OHDA选择性损毁大鼠黑质多巴胺能神经元,可造成与PD患者相似的基本病理变化,建立起可靠而稳定的PD大鼠模型.     

Mn enhancement and respiratory gating for in utero MRI of the embryonic mouse central nervous system.

The mouse is the preferred model organism for genetic studies of mammalian brain development. MRI has potential for in utero studies of mouse brain development, but has been limited previously by challenges of maximizing image resolution and contrast while minimizing artifacts due to physiological motion. Manganese (Mn)-enhanced MRI (MEMRI) studies have demonstrated central nervous system (CNS) contrast enhancement in mice from the earliest postnatal stages. The purpose of this study was to expand MEMRI to in utero studies of the embryonic CNS in combination with respiratory gating to decrease motion artifacts. We investigated MEMRI-facilitated CNS segmentation and three-dimensional (3D) analysis in wild-type mouse embryos from midgestation, and explored effects of Mn on embryonic survival and image contrast. Motivated by observations that MEMRI provided an effective method for visualization and volumetric analysis of embryonic CNS structures, especially in ventral regions, we used MEMRI to examine Nkx2.1 mutant mice that were previously reported to have ventral forebrain defects. Quantitative MEMRI analysis of Nkx2.1 knockout mice demonstrated volumetric changes in septum (SE) and basal ganglia (BG), as well as alterations in hypothalamic structures. This method may provide an effective means for in utero analysis of CNS phenotypes in a variety of mouse mutants.     

In vivo detection of excitotoxicity by manganese-enhanced MRI: comparison with physiological stimulation

Manganese-enhanced MRI (MEMRI) is a powerful technique for the in vivo monitoring of brain function in animals. Manganese enters into cells through calcium channels, i.e., voltage-gated calcium channels and activated glutamate receptors (e.g., N-methyl-D-aspartate receptors). N-methyl-D-aspartate receptors are activated both in normal physiological and pathophysiological conditions. Consistent with these mechanisms, we showed that in the olfactory bulb, the MEMRI signal strongly increases when excitotoxic mechanisms are induced by an administration of a N-methyl-D-aspartate receptor agonist, quinolinate. We found that the intensity of the MEMRI signal in excitotoxic conditions is similar to the odor-evoked signal in normal physiological conditions. Finally, we showed that the dynamics of the MEMRI signal are determined by the early phase of manganese in the olfactory bulb. Overall, these data show that, in addition to physiological studies, MEMRI can be used as an in vivo method to follow-up the dynamics of excitotoxic events.     

Axonal tracing of the normal and regenerating visual pathway of mouse,rat, frog,and fish using manganese‐enhanced MRI (MEMRI)

Purpose:

To assess optic nerve (ON) regeneration after injury by applying manganese‐enhanced MRI (MEMRI) in a study of comparative physiology between nonregenerating rat and mouse species and regenerating frog and fish species.

Materials and Methods:

The normal visual projections of rats, mice, frogs, and fish was visualized by intravitreal MnCl₂ injection followed by MRI. Rats and mice with ON crush (ONC) were divided into nonregenerating (ONC only), and regenerating animals with peripheral nerve graft (ONC+PNG; rats) or lens injury (ONC+LI; mice) and monitored by MEMRI at 1 and 20 days post‐lesion (dpl). Frog and fish with ON transection (ONT) were monitored by MEMRI up to 6 months postlesion (mpl).

Results:

Signal intensity profiles of the Mn²⁺‐enhanced ON were consistent with ON regeneration in the ONC+PNG and ONC+LI rat and mice groups, respectively, compared with the nonregenerating ONC groups. Furthermore, signal intensity profiles of the Mn²⁺‐enhanced ON obtained between 1 mpl and 6 mpl in the fish and frog groups, respectively, were consistent with spontaneous, complete ON regeneration.

Conclusion:

Taken together, these results demonstrate that MEMRI is a viable method for serial, in vivo monitoring of normal, induced, and spontaneously regenerating optic nerve axons in different species. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.     

Confounding neurodegenerative effects of manganese for in vivo MR imaging in rat models of brain insults

Purpose:

To examine the long‐term consequences of manganese exposure due to the use of manganese‐enhanced magnetic resonance imaging (MEMRI) in a model of closed head injury, the fluid‐percussion injury (FPI) model.

Materials and Methods:

Two groups of adult male Wistar rats (n = 72) were studied with either MEMRI, whereby rats receive MnCl₂ (100 mg/kg intraperitoneally) 24 hours prior to scanning, or standard MRI (sMRI) with no contrast agent. Rats from both groups underwent FPI or sham injury and were longitudinally assessed for 6 months for neurological toxicity using behavioral tests, EEG recording, and MRI scanning.

Results:

Regardless of whether they received FPI, MEMRI animals showed progressive signs of cerebral toxicity compared with sMRI rats, including significantly reduced weight gain, progressive brain volume decrease, and increased anxiety and depressive‐like behaviors.

Conclusion:

Long‐term structural and functional consequences of using manganese as a contrast agent for MRI can confound experimental outcomes and must be taken into account when designing longitudinal imaging studies using manganese‐enhanced MRI. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.     

Proton MRS of the unilateral substantia nigra in the human brain at 4 tesla: detection of high GABA concentrations.

Parkinson's disease (PD) is characterized by loss of dopaminergic neurons in the substantia nigra (SN), the cause of which is unknown. Characterization of early SN pathology could prove beneficial in the treatment and diagnosis of PD. The present study shows that with the use of short-echo (5 ms) Stimulated-Echo Acquisition Mode (STEAM) spectroscopy and LCModel, a neurochemical profile consisting of 10 metabolites, including gamma-aminobutyric acid (GABA), glutamate (Glu), and glutathione (GSH), can be measured from the unilateral SN at 4 tesla. The neurochemical profile of the SN is unique and characterized by a fourfold higher GABA/Glu ratio compared to the cortex, in excellent agreement with established neurochemistry. The presence of elevated GABA levels in SN was validated with the use of editing, suggesting that partial volume effects were greatly reduced. These findings establish the feasibility of obtaining a neurochemical profile of the unilateral human SN by single-voxel spectroscopy in small volumes.     

Dopaminergic neuron destruction reduces hippocampal serotonin 1A receptor uptake of trans-[18F]Mefway

The purpose of the present study is to investigate the relationship between dopaminergic neuron destruction and 5-HT system changes in a hemiparkinsonian rat model. We performed PET imaging studies with trans-[¹⁸F]Mefway in a hemiparkinsonian model of unilateral 6-hydroxydopamine (6-OHDA) rats. Region-of-interests (ROIs) were drawn in the hippocampus (HP) and cerebellum (CB). HP uptake, the ratios of specific binding to non-specific binding in the HP, and non-displaceable binding potential (BP_ND) in the HP were compared between 6-OHDA and control rats. As a result, unilateral 6-OHDA-lesioned rats exhibited significant bilateral reduction of HP uptake and trans-[¹⁸F]Mefway BP_ND compared to the intact control group. Therefore, the results demonstrate that destruction of the dopaminergic system causes the reduction of the serotonergic system.     

阿扑吗啡阻抗6-羟基多巴胺毁损纹状体的实验研究

 目的 探讨阿扑吗啡是否对6-羟基多巴胺毁损纹状体帕金森病鼠模型有神经保护作用.方法 6-羟基多巴胺毁损大鼠左侧纹状体,在毁损前15 min阿扑吗啡(10mg/kg,皮下注射),连续注射11 d.毁损2周后,分别进行行为学(苯丙胺引起的旋转数目)和神经化学(高压液相测定纹状体多巴胺及代谢物含量)的研究.结果 阿扑吗啡能降低苯丙胺引起的向损伤侧旋转的数目.而且,显著减低多巴胺的损耗使其恢复到正常,并使DOPAC/DA比率恢复到正常.结论 在6-羟基多巴胺毁损纹状体模型中,阿扑吗啡不仅改善运动功能,而且,恢复纹状体的多巴胺含量.     

Masthead,Volume 69, Issue 3

Manganese (Mn)‐enhanced MRI (MEMRI) has found a growing number of applications in anatomical and functional imaging in small animals, based on the cellular uptake of Mn ions in the brain, heart, and other organs. Previous studies have relied on endogenous mechanisms of paramagnetic Mn ion uptake and enhancement. To genetically control MEMRI signals, we reverse engineered a major component of the molecular machinery involved in Mn uptake, the divalent metal transporter, DMT1. DMT1 provides positive cellular enhancement in a manner that is highly sensitive and dynamic, allowing greater spatial and temporal resolution for MRI compared to previously proposed MRI reporters such as ferritin. We characterized the MEMRI signal enhancement properties of DMT1‐expressing cells, both in vitro and in vivo in mouse models of cancer and brain development. Our results show that DMT1 provides an effective genetic MRI reporter for a wide range of biological and preclinical imaging applications. Magn Reson Med 70:842–850, 2013. © 2012 Wiley Periodicals, Inc.     

Divalent metal transporter,DMT1: A novel MRI reporter protein

Manganese (Mn)‐enhanced MRI (MEMRI) has found a growing number of applications in anatomical and functional imaging in small animals, based on the cellular uptake of Mn ions in the brain, heart, and other organs. Previous studies have relied on endogenous mechanisms of paramagnetic Mn ion uptake and enhancement. To genetically control MEMRI signals, we reverse engineered a major component of the molecular machinery involved in Mn uptake, the divalent metal transporter, DMT1. DMT1 provides positive cellular enhancement in a manner that is highly sensitive and dynamic, allowing greater spatial and temporal resolution for MRI compared to previously proposed MRI reporters such as ferritin. We characterized the MEMRI signal enhancement properties of DMT1‐expressing cells, both in vitro and in vivo in mouse models of cancer and brain development. Our results show that DMT1 provides an effective genetic MRI reporter for a wide range of biological and preclinical imaging applications. Magn Reson Med 70:842–850, 2013. © 2012 Wiley Periodicals, Inc.     

Uptake and washout of I-123-MIBG in neuronal and non-neuronal sites in rat hearts: Relationship to renal clearance

We investigated the uptake and washout of I-123-metaiodobenzylguanidine (MIBG) in neuronal (both intra- and extravesicular) and non-neuronal sites in the heart and its relationship to renal clearance. Acute renal failure was induced in rats by ligating the renal vessels, and the findings were compared with those of sham-operated rats. Each group consisted of control, reserpine-treated and 6-hydroxydopamine (6-OHDA)-treated subgroups. Rats were sacrificed at 10 minutes and 4 hours after injection of MIBG. MIBG activity was calculated in specimens of heart, spleen, lung and blood. At 10 minutes, no significant difference in MIBG uptake in the heart was observed among the subgroups or between sham-operated and renal failure rats despite a significantly higher blood MIBG activity in the latter. At 4 hours, however, the hearts of both reserpine-treated and 6-OHDA-treated rats showed significantly lower MIBG uptake than control rats. Furthermore, the hearts of renal failure rats showed higher MIBG uptake in the control and reserpine-treated rats than in the corresponding subgroups in sham-operated rats. Intra and extravesicular neuronal uptake of MIBG in the heart were estimated using control, reserpine-treated and 6-OHDA-treated rats. Vesicular uptake values were similar in both the sham-operated group (0.51% ID/g) and the renal failure group (0.44% ID/g). But extravesicular neuronal uptake values were quite different in the renal failure group (0.86% ID/g) and the sham-operated group (0.19% ID/g). In conclusion, uptake to and washout from extravesicular neuronal sites may depend on the concentration of MIBG in the blood or the state of renal clearance, but vesicular uptake may be independent of these factors.     

高场强~1H-MRS对帕金森病大鼠模型的应用价值探讨

目的:利用高场强氢质子磁共振波谱(1H-MRS)观察帕金森病大鼠模型纹状体区的神经代谢变化,探讨高场强1H-MRS对PD大鼠模型的应用价值。方法:7只正常大鼠经6-羟基多巴胺(6-OHDA)单侧(右侧)损毁制备偏侧帕金森病模型前后应用1.5T磁共振进行波谱分析。分析造模术前后双侧纹状体区N-乙酰天门冬氨酸/肌酸(NAA/Cr)、胆碱/肌酸(Cho/Cr)比值的变化。并对黑质致密部进行黑质酪氨酸羟化酶免疫组织化学染色。结果:6只大鼠造模成功。损毁侧纹状体内NAA/Cr比值明显低于对侧及造模前同侧(P<0.05),而Cho/Cr比值与对侧及造模前同侧相比无显著性差异(P>0.05)。损毁侧黑质酪氨酸羟化酶阳性神经元较对侧显著减少(P<0.05)。结论:1.5T临床专用型磁共振1H-MRS可以作为帕金森病大鼠模型纹状体区细胞代谢有价值的无创性检测方法。     

Visualization of cortical spreading depression using manganese-enhanced magnetic resonance imaging.

Cortical spreading depression (CSD) was visualized using manganese-enhanced MRI (MEMRI) following topical application of KCl to the exposed rat cortex. MEMRI signal increase in the ipsilateral cortex relative to the contralateral control region was 60 +/- 30% following two KCl applications. MEMRI signal increase for a single (40%) versus double (80%) KCl application suggests an integration effect over successive CSD episodes. CSD-induced MEMRI enhancement involved cortical layers containing dense regions of apical dendrites, supporting the contention that these neuronal structures are necessary for propagation of CSDs. Subcortical enhancement was present in hippocampal and thalamic regions, most likely a result of neuronal connections with cortical layers 4 and 5. These results are consistent with previous studies of CSD using diffusion-weighted MRI and T(2) (*)-weighted MRI and should be useful for investigating CSD itself and its role in other neurologic disorders.     

Dependence of cardiac 11C-meta-hydroxyephedrine retention on norepinephrine transporter density.

The norepinephrine analog (11)C-meta-hydroxyephedrine (HED) is used with PET to map the regional distribution of cardiac sympathetic neurons. HED is rapidly transported into sympathetic neurons by the norepinephrine transporter (NET) and stored in vesicles. Although much is known about the neuronal mechanisms of HED uptake and retention, there is little information about the functional relationship between HED retention and cardiac sympathetic nerve density. The goal of this study was to characterize the dependence of HED retention on nerve density in rats with graded levels of cardiac denervation induced chemically with the neurotoxin 6-hydroxydopamine (6-OHDA). METHODS: Thirty male Sprague-Dawley rats were divided into 6 groups, and each group was administered a different dose of 6-OHDA: 0 (controls), 7, 11, 15, 22, and 100 mg/kg intraperitoneally. One day after 6-OHDA injection, HED (3.7-8.3 MBq) was injected intravenously into each animal and HED concentrations in heart and blood at 30 min after injection were determined. Heart tissues were frozen and later processed by tissue homogenization and differential centrifugation into a membrane preparation for in vitro measurement of cardiac NET density. A saturation binding assay using (3)H-mazindol as the radioligand was used to measure NET density (maximum number of binding sites [B(max)], fmol/mg protein) for each heart. RESULTS: In control animals, NET B(max) was 388 +/- 23 fmol/mg protein and HED heart uptake (HU) at 30 min was 2.89% +/- 0.35 %ID/g (%ID/g is percentage injected dose per gram tissue). The highest 6-OHDA dose of 100 mg/kg caused severe cardiac denervation, decreasing both NET B(max) and HED HU to 8% of their control values. Comparing values for all doses of 6-OHDA, HED retention had a strong linear correlation with NET density: HU = 0.0077B(max) -0.028, r(2) = 0.95. CONCLUSION: HED retention is linearly dependent on NET density in rat hearts that have been chemically denervated with 6-OHDA, suggesting that HED retention is a good surrogate measure of NET density in the rat heart. This finding is discussed in relation to clinical observations of the dependence of HED retention on cardiac nerve density in human subjects using PET.     

Time-Shift Homotopic Connectivity in Mesial Temporal Lobe Epilepsy

BACKGROUND AND PURPOSE:Voxel-mirrored intrinsic functional connectivity allows the depiction of interhemispheric homotopic connections in the human brain, whereas time-shift intrinsic functional connectivity allows the detection of the extent of brain injury by measuring hemodynamic properties. We combined time-shift voxel-mirrored homotopic connectivity analyses to investigate the alterations in homotopic connectivity in mesial temporal lobe epilepsy and assessed the value of applying this approach to epilepsy lateralization and the prediction of surgical outcomes in mesial temporal lobe epilepsy.MATERIALS AND METHODS:Resting-state functional MR imaging data were acquired from patients with unilateral mesial temporal lobe epilepsy (n = 62) (31 left- and 31 right-side) and healthy controls (n = 33). Dynamic interhemispheric homotopic architecture seeding from each hemisphere was individually calculated by 0, 1, 2, and 3 repetition time time-shift voxel-mirrored homotopic connectivity. Voxel-mirrored homotopic connectivity maps were compared between the patient and control groups by using 1-way ANOVA for each time-shift condition, separately. Group comparisons were further performed on the laterality of voxel-mirrored homotopic connectivity in each time-shift condition. Finally, we correlated the interhemispheric homotopic connection to the surgical outcomes in a portion of the patients (n = 20).RESULTS:The patients with mesial temporal lobe epilepsy showed decreased homotopic connectivity in the mesial temporal structures, temporal pole, and striatum. Alterations of the bihemispheric homotopic connectivity were lateralized along with delays in the time-shift in mesial temporal lobe epilepsy. The patients with unsuccessful surgical outcomes presented larger interhemispheric voxel-mirrored homotopic connectivity differences.CONCLUSIONS:This study showed whole patterns of dynamic alterations of interhemispheric homotopic connectivity in mesial temporal lobe epilepsy, extending the knowledge of abnormalities in interhemispheric connectivity in this condition. Time-shift voxel-mirrored homotopic connectivity has the potential for lateralization of unilateral mesial temporal lobe epilepsy and may have the capability of predicting surgical outcomes in this condition.

Interhemispheric communication and coordination facilitate information processing in the human brain.^1,2 Thus homotopic connections represent a fundamental characteristic of brain anatomy and function^3,4 and have been considered an important indicator for depicting the physiologic and pathologic features of the brain. On the basis of resting-state functional MR imaging measurements, an approach based on voxel-mirrored homotopic connectivity (VMHC) quantifies the interhemispheric homotopic connections by measuring the functional connectivity between each voxel in 1 hemisphere and its mirrored counterpart.⁵ Zuo et al⁵ found age-related increases in interhemispheric functional connectivity in the primary sensorimotor areas and decreases in the higher order processing areas, which provided insight into the evolution of brain development. Studies have also revealed specific alterations of homotopic connection in a cohort of brain diseases.^6–8 Decreased VMHC in schizophrenia has been suggested to reflect the substantial impairment of interhemiespheric coordination in these patients.⁶ Anderson et al⁷ found homotopic connectivity alterations related to behavioral and developmental abnormalities in autism.⁷ More recently, studies have further correlated functional homotopic connectivity with microstructural impairment in multiple sclerosis⁸ and idiopathic generalized epilepsy.⁹In contrast to the brain disorders featuring abnormal connection pathways as mentioned above,^6,8 mesial temporal lobe epilepsy (mTLE) is a location-related disease characterized by hippocampal sclerosis.¹⁰ Unilateral mTLE can cause bilateral and distributed brain impairments due to seizure propagation via the mesial temporal epileptic network.^11–13 Resting-state fMRI studies have shown asymmetric connections between bihemispheres^14–16 and decreased connectivity between bilateral hippocampi in mTLE.^17,18 These findings suggest that there are intra- and interhemispheric connection abnormalities in unilateral mTLE. However, neither the homotopic alterations of whole-brain functional connectivity nor the relationship between asymmetric lesions and interhemispheric communication in this disease has been investigated.fMRI-based VMHC provides a feasible way to observe the whole-brain homotopic connectivity alterations in mTLE. However, the conventional nondirectional functional connectivity measure, as used in VMHC, cannot detect the connection abnormalities resulting from deficits of the seed or target region. Recently, Lv et al¹⁹ proposed a time-shift (ts) analysis for resting-state functional connectivity. They quantified the temporal shift correlation between time courses of each voxel and global mean signal¹⁹ and correlated the time shifts with the extent and degree of perfusion delay in patients with stroke.^19,20 In addition, our previous study used time-shift correlation analysis to demonstrate the sequential effects of epileptic discharges on intrinsic network connectivity in children with absence epilepsy.²¹ Thus, time-shift delays in resting-state spontaneous connectivity were assumed to reflect brain hemodynamics and could measure the degree of brain injury; time-shift analysis also provides directional information as a measure of functional connectivity.²¹ In the current work, we combined the time-shift connectivity with the VMHC technique and applied them to resting-state fMRI data from patients with unilateral mTLE. We hypothesized that this strategy would allow us to assess the whole-brain homotopic connection impairments resulting from different hemispheres and may potentially be a tool for epileptic focus lateralization and surgical outcome prediction in mTLE.     

In vivo myocardial infarct area at risk assessment in the rat using manganese enhanced magnetic resonance imaging (MEMRI) at 1.5T.

The aim of this study was to measure the myocardial area at risk in rat, using MRI and manganese injection during a coronary occlusion/reperfusion model at 1.5T. A sequential protocol with occlusion and MnCl2 injection immediately followed by MRI was used with the assumption that MnCl2-induced contrast persistence is enough to accurately image the area at risk 90 min after occlusion. A total of 15 adult rats underwent a single 30-min episode of coronary occlusion followed by reperfusion. MnCl2 was injected (25 micromol/kg) at the beginning of the occlusion for 11 rats (group 1) and 6 h after reperfusion for four animals (group 2). A deficit of signal enhancement was observed in all rats. Hypoenhancement area in group 1 was correlated to the area at risk delineated by methylene blue (r=0.96, P<0.0001) whereas in group 2 it was correlated to the infarct area given by triphenyltetrazolium chloride (TTC) solution (r=0.98, P=0.003). The area at risk size was significantly correlated with left ventricle ejection fraction (LVEF), end-systolic volume and anterolateral wall thickening. This work demonstrates that hypoenhanced zone obtained after manganese injection during occlusion represents the area at risk and not only the infarct zone.     

Manganese-enhanced MRI of the optic visual pathway and optic nerve injury in adult rats

PURPOSE: To evaluate manganese (Mn2+)-enhanced MRI in a longitudinal study of normal and injured rat visual projections. MATERIALS AND METHODS: MRI was performed 24 hours after unilateral intravitreal injection of MnCl2 (150 nmol) into adult Fischer rats that were divided into four groups: 1) controls (N = 5), 2) dose-response (N = 10, 0.2-200 nmol), 3) time-response with repeated MRI during 24-168 hours post injection (N = 4), and 4) optic nerve crush (ONC) immediately preceding the MnCl2 injection (N = 7). Control and ONC animals were reinjected with MnCl2 20 days after the first injection, and MRI was performed 24 hours later. RESULTS: In the control group, the optic projection was visualized from the retina to the superior colliculus, with indications of transsynaptic transport to the cortex. There was a semilogarithmic relationship between the Mn2+ dose and Mn2+ enhancement from 4 to 200 nmol, and the enhancement decayed gradually to 0 by 168 hours. No Mn2+-enhanced signal was detected distal to the ON crush site. In the control group, similar enhancement was obtained after the first and second MnCl2 injections, while in the ONC group the enhancement proximal to the crush site was reduced 20 days post lesion (20 dpl). CONCLUSION: Mn2+-enhanced MRI is a viable method for temporospatial visualization of normal and injured ON in the adult rat. The observed reduction in the Mn2+ signal proximal to the ONC is probably a result of retrograde damage to the retinal ganglion cells, and not of Mn2+ toxicity.