Axonal injury detected by in vivo diffusion tensor imaging correlates with neurological disability in a mouse model of multiple sclerosis

Recent studies have suggested that axonal damage, and not demyelination, is the primary cause of long-term neurological impairment in multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). The axial and radial diffusivities derived from diffusion tensor imaging have shown promise as non-invasive surrogate markers of axonal damage and demyelination, respectively. In this study, in vivo diffusion tensor imaging of the spinal cords from mice with chronic EAE was performed to determine if axial diffusivity correlated with neurological disability in EAE assessed by the commonly used clinical scoring system. Axial diffusivity in the ventrolateral white matter showed a significant negative correlation with EAE clinical score and was significantly lower in mice with severe EAE than in mice with moderate EAE. Furthermore, the greater decreases in axial diffusivity were associated with greater amounts of axonal damage, as confirmed by quantitative staining for non-phosphorylated neurofilaments (SMI32). Radial diffusivity and relative anisotropy could not distinguish between the groups of mice with moderate EAE and those with severe EAE. The results further the notion that axial diffusivity is a non-invasive marker of axonal damage in white matter and could provide the necessary link between pathology and neurological disability.     

Diffusion tensor imaging detects treatment effects of FTY720 in experimental autoimmune encephalomyelitis mice

Fingolimod (FTY720) is an orally available sphingosine‐1‐phosphate (S1P) receptor modulator reducing relapse frequency in patients with relapsing–remitting multiple sclerosis (RRMS). In addition to immunosuppression, neuronal protection by FTY720 has also been suggested, but remains controversial. Axial and radial diffusivities derived from in vivo diffusion tensor imaging (DTI) were employed as noninvasive biomarkers of axonal injury and demyelination to assess axonal protection by FTY720 in experimental autoimmune encephalomyelitis (EAE) mice. EAE was induced through active immunization of C57BL/6 mice using myelin oligodendrocyte glycoprotein peptide 35–55 (MOG_35–55). We evaluated both the prophylactic and therapeutic treatment effect of FTY720 at doses of 3 and 10 mg/kg on EAE mice by daily clinical scoring and end‐point in vivo DTI. Prophylactic administration of FTY720 suppressed the disease onset and prevented axon and myelin damage when compared with EAE mice without treatment. Therapeutic treatment by FTY720 did not prevent EAE onset, but reduced disease severity, improving axial and radial diffusivity towards the control values without statistical significance. Consistent with previous findings, in vivo DTI‐derived axial and radial diffusivity correlated with clinical scores in EAE mice. The results support the use of in vivo DTI as an effective outcome measure for preclinical drug development. Copyright © 2013 John Wiley & Sons, Ltd.     

Diffusion tensor imaging detects axonal injury in a mouse model of repetitive closed-skull traumatic brain injury

Mild traumatic brain injuries (TBI) are common in athletes, military personnel, and the elderly, and increasing evidence indicates that these injuries have long-term health effects. However, the difficulty in detecting these mild injuries in vivo is a significant impediment to understanding the underlying pathology and treating mild TBI. In the following experiments, we present the results of diffusion tensor imaging (DTI) and histological analysis of a model of mild repetitive closed-skull brain injury in mouse. Histological markers used included silver staining and amyloid precursor protein (APP) immunohistochemistry to detect axonal injury, and Iba-1 immunohistochemistry to assess microglial activation. At 24h post-injury, before silver staining or microglial abnormalities were apparent by histology, no significant changes in any of the DTI parameters were observed within white matter. At 7 days post-injury we observed a reduction in axial and mean diffusivity. Relative anisotropy at 7 days correlated strongly with the degree of silver staining. Interestingly, APP was not observed at any timepoint examined. In addition to the white matter alterations, mean diffusivity was elevated in ipsilateral cortex at 24h but returned to sham levels by 7 days. Altogether, this demonstrates that DTI is a sensitive method for detecting axonal injury despite a lack of conventional APP pathology. Further, this reflects a need to better understand the histological basis for DTI signal changes in mild TBI.     

Noninvasive detection of brainstem and spinal cord axonal degeneration in an amyotrophic lateral sclerosis mouse model

Degeneration of motor neurons and their associated axons is a hallmark of amyotrophic lateral sclerosis, but reliable noninvasive lesion detection is lacking. In vivo diffusion tensor imaging was performed to evaluate neurodegeneration in the brainstem and cervical spinal cord of wild-type and G93A-SOD1 transgenic mice, an animal model of amyotrophic lateral sclerosis. A statistically significant reduction in the apparent diffusion coefficient was observed in the motor nuclei VII and XII of G93A-SOD1 transgenic mice relative to wild-type mice. No significant difference in diffusion anisotropy was observed in dorsal white or gray matter in cervical and lumbar segments of the spinal cord. In contrast, statistically significant decreases in axial diffusivity (diffusivity parallel to the axis of the spinal cord) and apparent diffusion coefficient were found in the ventrolateral white matter of G93A-SOD1 mice in both the cervical and lumbar spinal cord. The reduction in axial diffusivity, suggestive of axonal injury, in the white matter of the spinal cord of G93A-SOD1 mice was verified by immunostaining with nonphosphorylated neurofilament. The present study demonstrates that in vivo diffusion tensor imaging-derived axial diffusivity may be used to accurately evaluate axonal degeneration in an animal model of amyotrophic lateral sclerosis.     

In vivo diffusion MRI detects early spinal cord axonal pathology in a mouse model of amyotrophic lateral sclerosis

Diffusion magnetic resonance imaging (MRI) exhibits contrast that identifies macro‐ and microstructural changes in neurodegenerative diseases. Previous studies have shown that MR diffusion tensor imaging (DTI) can observe changes in spinal cord white matter in animals and humans affected with symptomatic amyotrophic lateral sclerosis (ALS). The goal of this preclinical work was to investigate the sensitivity of DTI for the detection of signs of tissue damage before symptoms appear. High‐field MRI data were acquired using a 9.4‐T animal scanner to examine the spinal cord of an ALS mouse model at pre‐ and post‐symptomatic stages (days 80 and 120, respectively). The MRI results were validated using yellow fluorescent protein (YFP) via optical microscopy of spinal cord tissue slices collected from the YFP,G93A‐SOD1 mouse strain. DTI maps of diffusion‐weighted imaging (DWI) signal intensity, mean diffusivity (MD), fractional anisotropy (FA), axial diffusivity (AD) and radial diffusivity (RD) were computed for axial slices of the lumbar region of the spinal cord. Significant changes were observed in FA (6.7% decrease, p < 0.01), AD (19.5% decrease, p < 0.01) and RD (16.1% increase, p < 0.001) at postnatal day 80 (P80). These differences were correlated with changes in axonal fluorescence intensity and membrane cellular markers. This study demonstrates the value of DTI as a potential tool to detect the underlying pathological progression associated with ALS, and may accelerate the discovery of therapeutic strategies for patients with this disease.     

Diffusion tensor imaging of diffuse axonal injury in a rat brain trauma model

Diffusion tensor imaging (DTI) was used to study traumatic brain injury. The impact-acceleration trauma model was used in rats. Here, in addition to diffusivities (mean, axial and radial), fractional anisotropy (FA) was used, in particular, as a parameter to characterize the cerebral tissue early after trauma. DTI was implemented at 7 T using fast spiral k-space sampling and the twice-refocused spin echo radiofrequency sequence for eddy current minimization. The method was carefully validated on different phantom measurements. DTI of a trauma group (n = 5), as well as a sham group (n = 5), was performed at different time points during 6 h following traumatic brain injury. Two cerebral regions, the cortex and corpus callosum, were analyzed carefully. A significant decrease in diffusivity in the trauma group versus the sham group was observed, suggesting the predominance of cellular edema in both cerebral regions. No significant FA change was detected in the cortex. In the corpus callosum of the trauma group, the FA indices were significantly lower. A net discontinuity in fiber reconstructions in the corpus callosum was observed by fiber tracking using DTI. Histological analysis using Hoechst, myelin basic protein and Bielschowsky staining showed fiber disorganization in the corpus callosum in the brains of the trauma group. On the basis of our histology results and the characteristics of the impact-acceleration model responsible for the presence of diffuse axonal injury, the detection of low FA caused by a drastic reduction in axial diffusivity and the presence of fiber disconnections of the DTI track in the corpus callosum were considered to be related to the presence of diffuse axonal injury.     

Diffusion basis spectrum imaging detects and distinguishes coexisting subclinical inflammation,demyelination and axonal injury in experimental autoimmune encephalomyelitis mice

Clinicopathological paradox has hampered significantly the effective assessment of the efficacy of therapeutic intervention for multiple sclerosis. Neuroimaging biomarkers of tissue injury could guide more effective treatment by accurately reflecting the underlying subclinical pathologies. Diffusion tensor imaging‐derived directional diffusivity and anisotropy indices have been applied to characterize white matter disorders. However, these biomarkers are sometimes confounded by the complex pathologies seen in multiple sclerosis and its animal models. Recently, a novel technique of diffusion basis spectrum imaging has been developed to quantitatively assess axonal injury, demyelination and inflammation in a mouse model of inflammatory demyelination. Lenaldekar, which inhibits T‐cell expansion in a non‐cytolytic manner, has been shown to suppress relapses and preserve white matter integrity in mice with experimental autoimmune encephalomyelitis. In this study, relapsing–remitting experimental autoimmune encephalomyelitis was induced through active immunization of SJL/J mice with a myelin proteolipid protein peptide. The therapeutic efficacy of Lenaldekar treatment was evaluated via daily clinical score, cross‐sectional ex vivo diffusion basis spectrum imaging examination and histological analysis. Lenaldekar greatly reduced relapse severity and protected white matter integrity in these experimental autoimmune encephalomyelitis mice. Diffusion basis spectrum imaging‐derived axial diffusivity, radial diffusivity and restricted diffusion tensor fraction accurately reflected axonal injury, myelin integrity and inflammation‐associated cellularity change, respectively. These results support the potential use of diffusion basis spectrum imaging as an effective outcome measure for preclinical drug evaluation. Copyright © 2014 John Wiley & Sons, Ltd.     

Effect of Schwann cell transplantation combined with electroacupuncture on axonal regeneration and remyelination in rats with spinal cord injury

Axonal impairment and demyelination after compressed spinal cord injury lead to serious neurological dysfunction. Increasing studies have suggested that Schwann cells (SCs) transplantation is a reliable, effective, and promising method for treating spinal cord injury. However, single SCs transplantation is insufficient to promote the full recovery of neurological function. Additional approaches are required to support SCs transplantation as a treatment for spinal cord injury. In the study, we investigated whether the combination of electroacupuncture (EA) and SCs transplantation was a reliable intervention for spinal cord injury. We found that rats in the combination group had significantly higher functional locomotor scores than those received single treatment. By immunostaining, we found EA can not only improve survival and proliferation of transplanted SCs but also inhibit SC apoptosis and block the formation of an astrocytic scar. Additionally, EA promoted regenerated axons extending “bullet-shaped” growth cones into the lesion. Remarkably, EA can modify astrogliosis to promote axonal regeneration following SCs transplantation through inducing extension of astrocytic processes in the SCs graft interface. More importantly, the combination of SCs engraftment and EA can enhance corticospinal-tract axonal regeneration and remyelination after spinal cord injury through up-regulating neuregulin 1 type III in SCs and its downstream signaling mediators. Thus, it is concluded that SCs effectively promote axonal recovery after spinal cord injury when combined with EA stimulation. The experimental results have reinforced the theoretical basis of EA for its clinical efficacy in patients with spinal cord injury and merited further investigation for potential clinical application.     

The impact of myelination on axon sparing and locomotor function recovery in spinal cord injury assessed using diffusion tensor imaging

The dysmyelinated axons of shiverer mice exhibit impaired conduction characteristics, similar to early postnatal axons before myelination, whereas the patterns of neuronal activity and connectivity are relatively comparable with those of wild‐type myelinated axons. This unique dysmyelination pattern is exploited in the present study to determine the role of compact myelin in the loss and recovery of function following traumatic spinal cord injury (SCI). We applied in vivo diffusion tensor imaging (DTI) and post‐mortem immunohistochemistry analysis to examine changes in myelin and axonal integrity, and evaluated these changes in concert with the analysis of locomotor function from 1 to 4 weeks following a mid‐thoracic contusion injury in homozygous shiverer and heterozygous littermate mice. The DTI biomarkers, axial and radial diffusivities, are noninvasive indicators of axon and myelin integrity in response to SCI of both myelinated and dysmyelinated spinal cord. We show that myelin is critical for normal hind limb function in open field locomotion. However, when the functional outcome is limited during chronic SCI, the extent of recovery is associated with residual axonal integrity and independent of the extent of intact myelin at the lesion epicenter. Copyright © 2013 John Wiley & Sons, Ltd.     

Reproducibility of tract‐specific magnetization transfer and diffusion tensor imaging in the cervical spinal cord at 3 tesla

Damage to specific white matter tracts within the spinal cord can often result in the particular neurological syndromes that characterize myelopathies such as traumatic spinal cord injury. Noninvasive visualization of these tracts with imaging techniques that are sensitive to microstructural integrity is an important clinical goal. Diffusion tensor imaging (DTI)‐ and magnetization transfer (MT)‐derived quantities have shown promise in assessing tissue health in the central nervous system. In this paper, we demonstrate that DTI of the cervical spinal cord can reliably discriminate sensory (dorsal) and motor (lateral) columns. From data derived from nine healthy volunteers, two raters quantified column‐specific parallel (λ_||) and perpendicular (λ_?) diffusivity, fractional anisotropy (FA), mean diffusivity (MD), and MT‐weighted signal intensity relative to cerebrospinal fluid (MTCSF) over two time‐points separated by more than 1 week. Cross‐sectional means and standard deviations of these measures in the lateral and dorsal columns were as follows: λ_||: 2.13 ± 0.14 and 2.14 ± 0.11 μm²/ms; λ_?: 0.67 ± 0.16 and 0.61 ± 0.09 μm²/ms; MD: 1.15 ± 0.15 and 1.12 ± 0.08 μm²/ms; FA: 0.68 ± 0.06 and 0.68 ± 0.05; MTCSF: 0.52 ± 0.05 and 0.50 ± 0.05. We examined the variability and interrater and test‐retest reliability for each metric. These column‐specific MR measurements are expected to enhance understanding of the intimate structure‐function relationship in the cervical spinal cord and may be useful for the assessment of disease progression. Copyright © 2009 John Wiley & Sons, Ltd.     

Diffusion-weighted imaging of the entire spinal cord

In spite of their diagnostic potential, the poor quality of available diffusion-weighted spinal cord images often restricts clinical application to cervical regions, and improved spatial resolution is highly desirable. To address these needs, a novel technique based on the combination of two recently presented reduced field-of-view approaches is proposed, enabling high-resolution acquisition over the entire spinal cord. Field-of-view reduction is achieved by the application of non-coplanar excitation and refocusing pulses combined with outer volume suppression for removal of unwanted transition zones. The non-coplanar excitation is performed such that a gap-less volume is acquired in a dedicated interleaved slice order within two repetition times. The resulting inner volume selectivity was evaluated in vitro. In vivo diffusion tensor imaging data on the cervical, thoracic and lumbar spinal cord were acquired in transverse orientation in each of four healthy subjects. An in-plane resolution of 0.7 x 0.7 mm(2) was achieved without notable aliasing, motion or susceptibility artifacts. The measured mean +/- SD fractional anisotropy was 0.69 +/- 0.11 in the thoracic spinal cord and 0.75 +/- 0.07 and 0.63 +/- 0.08 in cervical and lumbar white matter, respectively.     

Diffusion tensor imaging of renal ischemia reperfusion injury in an experimental model

Renal ischemia reperfusion injury (IRI) is a major cause of acute renal failure. It occurs in various clinical settings such as renal transplantation, shock and vascular surgery. Serum creatinine level has been used as an index for estimating the degree of renal functional loss in renal IRI. However, it only evaluates the global renal function. In this study, diffusion tensor imaging (DTI) was used to characterize renal IRI in an experimental rat model. Spin‐echo echo‐planar DTI with b‐value of 300 s/mm² and 6 diffusion gradient directions was performed at 7 T in 8 Sprague‐Dawley (SD) with 60‐min unilateral renal IRI and 8 normal SD rats. Apparent diffusion coefficient (ADC), directional diffusivities and fractional anisotropy (FA) were measured at the acute stage of IRI. The IR‐injured animals were also examined by diffusion‐weighted imaging with 7 b‐values up to 1000 s/mm² to estimate true diffusion coefficient (D_true) and perfusion fraction (P_fraction) using a bi‐compartmental model. ADC of injured renal cortex (1.69 ± 0.24 × 10^?3 mm²/s) was significantly lower (p < 0.01) than that of contralateral intact cortex (2.03 ± 0.35 × 10^?3 mm²/s). Meanwhile, both ADC and FA of IR‐injured medulla (1.37 ± 0.27 × 10^?3 mm²/s and 0.28 ± 0.04, respectively) were significantly less (p < 0.01) than those of contralateral intact medulla (2.01 ± 0.38 × 10^?3 mm²/s and 0.36 ± 0.04, respectively). The bi‐compartmental model analysis revealed the decrease in D_true and P_fraction in the IR‐injured kidneys. Kidney histology showed widespread cell swelling and erythrocyte congestion in both cortex and medulla, and cell necrosis/apoptosis and cast formation in medulla. These experimental findings demonstrated that DTI can probe both structural and functional information of kidneys following renal IRI. Copyright © 2010 John Wiley & Sons, Ltd.     

减压对大鼠脊髓压迫性损伤后脱髓鞘病变和BDNF表达的影响

目的观察脑源性神经生长因子(BDNF)对脊髓压迫性损伤(CSCI)后有髓神经纤维脱髓鞘病变的影响,为阐明BDNF对神经纤维脱髓鞘病变修复提供实验基础。方法将大鼠均分成4组:正常组、假手术组、压迫组和减压组。用自行设计的压迫器制作大鼠脊髓压迫模型。压迫组作脊髓压迫12 h,减压组作脊髓压迫1 h,假手术组仅作脊髓显露,不作压迫。用锇酸染色观察CSCI后1、3和7 d有髓神经纤维变化情况;Western blot和免疫荧光双标检测BDNF和髓鞘碱性蛋白(MBP)的表达。结果压迫组和减压组都出现脱髓鞘病变,并随着时间的延长,髓鞘逐渐水肿、变性、MBP崩解。BDNF表达量在CSCI后随时间延长也逐渐降低(P0.05),但与压迫组相比较,减压组脱髓鞘病变较轻且MBP和BDNF降低幅度小而缓慢(P0.05)。结论 CSCI后尽早减压可减轻脱髓鞘的发生,且可能与BDNF的表达有关。     

Diffusion tensor imaging of white matter in the superior temporal gyrus and temporal stem in autism

Recent MRI studies have indicated that regions of the temporal lobe including the superior temporal gyrus (STG) and the temporal stem (TS) appear to be abnormal in autism. In this study, diffusion tensor imaging (DTI) measurements of white matter in the STG and the TS were compared in 43 autism and 34 control subjects. DTI measures of mean diffusivity, fractional anisotropy, axial diffusivity, and radial diffusivity were compared between groups. In all regions, fractional anisotropy was significantly decreased and both mean diffusivity and radial diffusivity were significantly increased in the autism group. These results suggest that white matter microstructure in autism is abnormal in these temporal lobe regions, which is consistent with theories of aberrant brain connectivity in autism.     

Assessment of the diagnostic value of diffusion tensor imaging in patients with spinal cord compression: a meta-analysis

We investigated the diagnostic value of the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) of magnetic resonance diffusion tensor imaging (DTI) in patients with spinal cord compression (SCC) using a meta-analysis framework. Multiple scientific literature databases were exhaustively searched to identify articles relevant to this study. Mean values and standardized mean differences (SMDs) were calculated for the ADC and FA in normal and diseased tissues. The STATA version 12.0 software was used for statistical analysis. Of the 41 articles initially retrieved through database searches, 11 case-control studies were eligible for the meta-analysis and contained a combined total of 645 human subjects (394 patients with SCC and 251 healthy controls). All 11 studies reported data on FA, and 9 contained data related to the ADC. The combined SMDs of the ADC and FA showed that the ADC was significantly higher and the FA was lower in patients with SCC than in healthy controls. Subgroup analysis based on the b value showed higher ADCs in patients with SCC than in healthy controls at b values of both ≤500 and >500 s/mm². In summary, the main findings of this meta-analysis revealed an increased ADC and decreased FA in patients with SCC, indicating that DTI is an important diagnostic imaging tool to assess patients suspected to have SCC.     

MR弥散张量成像在脊柱脊髓疾病诊断中应用的研究进展

目的 探讨MR弥散张量成像(DTI)在脊髓疾病诊断中的应用进展。方法 在PubMed、Springer Link、中国知网数据库中,以“弥散张量成像、脊髓疾病、椎间盘”关键词,查阅2003年1月—2014年12月有关MR-DTI在脊髓疾病应用进展的相关文献,进行分析和总结。结果 MR-DTI体现脊髓病变早期组织空间组成和各组织成分之间水交换功能的改变,并能显示神经纤维束的走行方向,反映脊髓束功能的完整性。MR-DTI已逐渐应用于脊髓型颈椎病的早期诊断、脊髓损伤时期的判断和腰骶椎神经根病变的诊断以及腰椎间盘退变的早期诊断。DTI应用于脊髓疾病的诊断时,由于存在脊髓体积过小、扫描时间过长、运动伪影等不足,阻碍其在脊髓疾病诊断领域的发展。目前,随着并行成像技术、单次激发快速自旋回波序列等新技术的应用,这些问题正在逐步得到解决。结论DTI已在脊柱脊髓领域发挥出常规MR检查不可替代的作用。随着影像学的进步、新技术的应用及经验的丰富,DTI应用存在的阻碍必将得到解决,DTI在脊髓疾病领域的应用具有广阔的前景。     

Region‐specific impairment of the cervical spinal cord (SC) in amyotrophic lateral sclerosis: A preliminary study using SC templates and quantitative MRI (diffusion tensor imaging/inhomogeneous magnetization transfer)

In this preliminary study, our objective was to investigate the potential of high‐resolution anatomical imaging, diffusion tensor imaging (DTI) and conventional/inhomogeneous magnetization transfer imaging [magnetization transfer (MT)/inhomogeneous magnetization transfer (ihMT)] at 3 T, analyzed with template‐extracted regions of interest, to measure the atrophy and structural changes of white (WM) and gray (GM) matter spinal cord (SC) occurring in patients with amyotrophic lateral sclerosis (ALS). Ten patients with ALS and 20 age‐matched healthy controls were recruited. SC GM and WM areas were automatically segmented using dedicated templates. Atrophy indices were evaluated from T ₂*‐weighted images at each vertebral level from cervical C1 to C6. DTI and ihMT metrics were quantified within the corticospinal tract (CST), posterior sensory tract (PST) and anterior GM (aGM) horns at the C2 and C5 levels. Clinical disabilities of patients with ALS were evaluated using the Revised ALS Functional Rating Scale, upper motor neuron (UMN) and Medical Research Council scorings, and correlated with MR metrics. Compared with healthy controls, GM and WM atrophy was observed in patients with ALS, especially at lower cervical levels, where a strong correlation was also observed between GM atrophy and the UMN score (R  = ?0.75, p  = 0.05 at C6). Interestingly, a significant decrease in ihMT ratio was found in all regions of interest (p  < 0.0008), fractional anisotropy (FA) and MT ratios decreased significantly in CST, especially at C5 (p  < 0.005), and λ_// (axial diffusivity) decreased significantly in CST (p  = 0.0004) and PST (p  = 0.003) at C2. Strong correlations between MRI metrics and clinical scores were also found (0.47 < |R | < 0.87, p  < 0.05). Altogether, these preliminary results suggest that high‐resolution anatomical imaging and ihMT imaging, in addition to DTI, are valuable for the characterization of SC tissue impairment in ALS. In this study, in addition to an important SC WM demyelination, we also observed, for the first time in ALS, impairments of cervical aGM.     

脐带间充质干细胞移植对脊髓损伤小鼠运动功能的修复和镇痛作用

目的：探讨人脐带间充质干细胞（ hUC-MSCs）移植缓解脊髓损伤神经病理性痛,并促进功能恢复的效果及 其与脊髓损伤小鼠胶质细胞活化及炎症因子水平的调控关系。方法：建立ICR 小鼠脊髓损伤模型,同时构建慢病毒 载体介导绿色荧光蛋白（ GFP）标记体外培养的 hUC-MSCs ;将模型小鼠分为模型组和治疗组,治疗组于脊髓损 伤1 周后采用局部注射 hUC-MSCs 移植到脊髓中,每周进行运动功能（ BBB）评分及机械性痛觉过敏检测,持续8 周后行组织学评价与炎症因子检测。结果：治疗组脊髓组织中 GFP 荧光有表达。BBB检测结果显示,治疗组和模 型组小鼠随时间延长运动功能均逐渐恢复,其中治疗组运动功能恢复速度要显著快于模型组;机械触诱发痛检测显 示,小鼠脊髓损伤后痛阈值降低,随着时间延长痛阈值逐渐升高。同一个时间点治疗组的痛阈值显著高于模型组。 与模型组相比,治疗组小鼠脊髓组织的白细胞介素-6（ IL-6）、肿瘤坏死因子-α（ TNF-α）表达下降,胶质细胞源 性神经营养因子（ GDNF）表达升高,同时脊髓组织巨噬细胞激活抗原1（ ED1/CD68） 荧光表达显著降低。结论： 脊髓损伤小鼠中hUC-MSCs 移植可能通过降低炎症因子 IL-6 和TNF-α 的分泌,提高 GDNF 的表达水平来促进受损 脊髓组织的修复,并发挥镇痛效应。     

Correlations of quantitative MRI metrics with myelin basic protein (MBP) staining in a murine model of demyelination

Myelin imaging in the central nervous system is essential for monitoring pathologies involving white matter alterations. Various quantitative MRI protocols relying on the modeling of the interactions of water protons with myelinated tissues have shown sensitivities in case of myelin disruption. Some extracted model parameters are more sensitive to demyelination, such as the bound pool fraction (f) in quantitative magnetization transfer imaging (qMTI), the radial diffusivity in diffusion tensor imaging (DTI), and the myelin water fraction (MWF) in myelin water imaging (MWI). A 3D ultrashort echo time (UTE) sequence within an appropriate water suppression condition (Diff‐UTE) is also considered for the direct visualization of the myelin semi‐solid matrix (Diff‐UTE normalized signal; rSPF). In this paper, we aimed at assessing the sensitivities and correlations of the parameters mentioned above to an immuno‐histological study of the myelin basic protein (MBP) in a murine model of demyelination at 7 T. We demonstrated a high sensitivity of the MRI metrics to demyelination, and strong Spearman correlations in the corpus callosum between histology, macromolecular proton fraction (ρ>0.87) and Diff‐UTE signal (ρ>0.76), but moderate ones with radial diffusivity and MWF (|ρ|<0.70).     

Short-scan-time multi-slice diffusion MRI of the mouse cervical spinal cord using echo planar imaging

Mouse spinal cord (SC) diffusion-weighted imaging (DWI) provides important information on tissue morphology and structural changes that may occur during pathologies such as multiple sclerosis or SC injury. The acquisition scheme of the commonly used DWI techniques is based on conventional spin-echo encoding, which is time-consuming. The purpose of this work was to investigate whether the use of echo planar imaging (EPI) would provide good-quality diffusion MR images of mouse SC, as well as accurate measurements of diffusion-derived metrics, and thus enable diffusion tensor imaging (DTI) and highly resolved DWI within reasonable scan times. A four-shot diffusion-weighted spin-echo EPI (SE-EPI) sequence was evaluated at 11.75 T on a group of healthy mice (n = 10). SE-EPI-derived apparent diffusion coefficients of gray and white matter were compared with those obtained using a conventional spin-echo sequence (c-SE) to validate the accuracy of the method. To take advantage of the reduction in acquisition time offered by the EPI sequence, multi-slice DTI acquisitions were performed covering the cervical segments (six slices, six diffusion-encoding directions, three b values) within 30 min (vs 2 h for c-SE). From these measurements, fractional anisotropy and mean diffusivities were calculated, and fiber tracking along the C1 to C6 cervical segments was performed. In addition, high-resolution images (74 x 94 microm(2)) were acquired within 5 min per direction. Clear delineation of gray and white matter and identical apparent diffusion coefficient values were obtained, with a threefold reduction in acquisition time compared with c-SE. While overcoming the difficulties associated with high spatially and temporally resolved DTI measurements, the present SE-EPI approach permitted identification of reliable quantitative parameters with a reproducibility compatible with the detection of pathologies. The SE-EPI method may be particularly valuable when multiple sets of images from the SC are needed, in cases of rapidly evolving conditions, to decrease the duration of anesthesia or to improve MR exploration by including additional MR measurements. Copyright (c) 2008 John Wiley & Sons, Ltd.