A Novel MRI Biomarker of Spinal Cord White Matter Injury: T2*-Weighted White Matter to Gray Matter Signal Intensity Ratio

BACKGROUND AND PURPOSE:DTI, magnetization transfer, T2*-weighted imaging, and cross-sectional area can quantify aspects of spinal cord microstructure. However, clinical adoption remains elusive due to complex acquisitions, cumbersome analysis, limited reliability, and wide ranges of normal values. We propose a simple multiparametric protocol with automated analysis and report normative data, analysis of confounding variables, and reliability.MATERIALS AND METHODS:Forty healthy subjects underwent T2WI, DTI, magnetization transfer, and T2*WI at 3T in <35 minutes using standard hardware and pulse sequences. Cross-sectional area, fractional anisotropy, magnetization transfer ratio, and T2*WI WM/GM signal intensity ratio were calculated. Relationships between MR imaging metrics and age, sex, height, weight, cervical cord length, and rostrocaudal level were analyzed. Test-retest coefficient of variation measured reliability in 24 DTI, 17 magnetization transfer, and 16 T2*WI datasets. DTI with and without cardiac triggering was compared in 10 subjects.RESULTS:T2*WI WM/GM showed lower intersubject coefficient of variation (3.5%) compared with magnetization transfer ratio (5.8%), fractional anisotropy (6.0%), and cross-sectional area (12.2%). Linear correction of cross-sectional area with cervical cord length, fractional anisotropy with age, and magnetization transfer ratio with age and height led to decreased coefficients of variation (4.8%, 5.4%, and 10.2%, respectively). Acceptable reliability was achieved for all metrics/levels (test-retest coefficient of variation < 5%), with T2*WI WM/GM comparing favorably with fractional anisotropy and magnetization transfer ratio. DTI with and without cardiac triggering showed no significant differences for fractional anisotropy and test-retest coefficient of variation.CONCLUSIONS:Reliable multiparametric assessment of spinal cord microstructure is possible by using clinically suitable methods. These results establish normalization procedures and pave the way for clinical studies, with the potential for improving diagnostics, objectively monitoring disease progression, and predicting outcomes in spinal pathologies.

The era of quantitative MR imaging has arrived, allowing in vivo measurement of specific physical properties reflecting spinal cord (SC) microstructure and tissue damage.^1,2 Such measures have potential clinical applications, including improved diagnostic tools, objective monitoring for disease progression, and prediction of clinical outcomes.³ However, technical challenges such as artifacts, image distortion, and achieving acceptable SNR have led to limited reliability. Specialized pulse sequences and custom hardware have advanced the field but incur costs of increased complexity and acquisition time while creating barriers to portability and clinical adoption. Furthermore, quantitative MR imaging metrics often show wide ranges of normal values and confounding relationships with subject characteristics such as age,^4–8 for which most previous studies have not accounted.³Among the most promising SC quantitative MR imaging techniques are DTI and magnetization transfer (MT).^1–3 These provide measures of axonal integrity and myelin quantity that correlate with functional impairment in conditions such as degenerative cervical myelopathy (DCM)^5–7,9 and MS,^3,9 albeit with limited physiologic specificity (eg, fractional anisotropy [FA] reflects both demyelination and axonal injury).^10,11 SC cross-sectional area (CSA) computed from high-resolution anatomic images can measure atrophy (eg, in MS)¹² or the degree of SC compression in DCM.¹³ T2*-weighted imaging at 3T or higher field strengths offers high resolution and sharp contrast between SC WM and GM, allowing segmentation between these structures similar to that in phase-sensitive inversion recovery.^14,15 T2*WI also demonstrates hyperintensity in injured WM,^16–18 reflecting demyelination, gliosis, and increased calcium and nonheme iron concentrations.¹⁹ T2*WI signal intensity is not an absolute quantity, so we normalize its value in WM by the average GM signal intensity in each axial section, creating a novel measure of WM injury: T2*WI WM/GM ratio.²⁰We propose a multiparametric approach to cervical SC quantitative MR imaging with clinically feasible methods, including acceptable acquisition times, standard hardware/pulse sequences, and automated image analysis. Our protocol yields 4 measures of SC tissue injury (CSA, FA, MT ratio [MTR], and T2*WI WM/GM), for which this study establishes normative values in numerous ROIs. We characterize the variation of these metrics with age, sex, height, weight, cervical cord length, and rostrocaudal level and propose normalization methods. Finally, we assess test-retest reliability of FA, MTR, and T2*WI WM/GM and compare our DTI results against those with cardiac triggering.     

Brain White Matter Involvement in Hereditary Spastic Paraplegias: Analysis with Multiple Diffusion Tensor Indices

BACKGROUND AND PURPOSE:The hereditary spastic paraplegias are a group of genetically heterogeneous neurodegenerative disorders, characterized by progressive spasticity and weakness of the lower limbs. Although conventional brain MR imaging findings are normal in patients with pure hereditary spastic paraplegia, microstructural alteration in the cerebral WM can be revealed with DTI. Concomitant investigation of multiple intrinsic diffusivities may shed light on the neurobiologic substrate of the WM degeneration pattern in patients with pure hereditary spastic paraplegia across the whole brain.MATERIALS AND METHODS:Tract-based spatial statistics analysis was performed to compare fractional anisotropy and mean, axial, and radial diffusivities of the WM skeleton in a group of 12 patients with pure hereditary spastic paraplegia and 12 healthy volunteers. Data were analyzed counting age and sex as nuisance covariates. The threshold-free cluster-enhancement option was applied, and the family-wise error rate was controlled by using permutation tests for nonparametric statistics.RESULTS:In pure hereditary spastic paraplegia, group widespread fractional anisotropy decreases and radial diffusivity and mean diffusivity increases (P < .05, corrected) were found. No voxelwise difference was observed for the axial diffusivity map. Percentage of voxels within the WM skeleton that passed the significance threshold were 51%, 41.6%, and 11.9%, respectively, for radial diffusivity, fractional anisotropy, and mean diffusivity clusters. An anteroposterior pattern with preferential decrease of fractional anisotropy in the frontal circuitry was detected.CONCLUSIONS:In patients with pure hereditary spastic paraplegia, alterations in multiple DTI indices were found. Radial diffusivity seems more sensitive to hereditary spastic paraplegia–related WM pathology and, in line with the lack of axial diffusivity changes, might indicate a widespread loss of myelin integrity. A decrease of fractional anisotropy alone in the frontal circuitry may reflect subtle disruption of the frontal connections.

The hereditary spastic paraplegias (HSPs), also called familial spastic paraparesis or Strümpell-Lorrain disease, represent a genetically and clinically heterogeneous group of neurodegenerative disorders.¹ The main clinical feature is progressive spasticity due to slowly progressing “dying back” axonal degeneration, which is maximal in the terminal portions of the longest descending and ascending tracts.² On the basis of clinical symptoms, HSPs are classified into pure or uncomplicated, in which the spastic paraplegia is the major clinical manifestation; and complex or complicated forms, presenting with additional neurologic signs, such as intellectual disability or cognitive decline, deafness, cerebellar ataxia, epilepsy, dysarthria, peripheral neuropathy, optic atrophy, and visual dysfunction.³ Autosomal dominant, autosomal recessive, or X-linked inheritance is associated with multiple genes or loci and leads to genetic heterogeneity of this disorder. The HSP loci are designated as spastic paraplegia loci and are numbered 1–56 according to their discovery.⁴ There is scarce evidence about the epidemiology of HSP, though its prevalence is estimated at 1.27:100,000 population in Europe.⁵Findings of conventional MR imaging of the brain are usually normal in pure hereditary spastic paraplegia (pHSP). In contrast, nonspecific findings such as cortical atrophy and subcortical and periventricular WM alterations are present in complicated HSP.⁶ Distinct MR imaging findings may accompany complicated HSP; for instance, a common form of autosomal recessive HSP with SPG11 mutation (linked to the 15q13-q15 chromosome) is frequently associated with a thin corpus callosum.⁷ Optic nerve and cerebellar atrophy may be revealed when visual symptoms and cerebellar ataxia are present.⁸DTI is an efficient technique used to characterize the in vivo microstructural organization of the WM.⁹ The common DTI indices are fractional anisotropy (FA) (sensitive to microstructural changes and associated with the presence of oriented structures in tissue) and mean diffusivity (MD) (characterizes mean-square displacement of molecules and the overall presence of obstacles to diffusion).¹⁰ Other indices, axial diffusivity (AD) and radial diffusivity (RD), offer suggestive elements to differentiate axonal injury and demyelination.¹¹ To extend our knowledge of the neurobiologic basis of WM pathology, using multiple diffusivity matrices (FA, MD, RD, and AD) is recommended.¹²The present study was set up to investigate WM alterations across the whole brain in a group of patients with pHSP with SPG4, SPG5, SPG3a, and SPG10 mutations, applying tract-based spatial statistics (TBSS) analysis with multiple DTI indices.     

Decreased T1 Contrast between Gray Matter and Normal-Appearing White Matter in CADASIL

BACKGROUND AND PURPOSE:CADASIL is the most frequent hereditary small-vessel disease of the brain. The clinical impact of various MR imaging markers has been repeatedly studied in this disorder, but alterations of contrast between gray matter and normal-appearing white matter remain unknown. The aim of this study was to evaluate the contrast alterations between gray matter and normal-appearing white matter on T1-weighted images in patients with CADASIL compared with healthy subjects.MATERIALS AND METHODS:Contrast between gray matter and normal-appearing white matter was assessed by using histogram analyses of 3D T1 high-resolution MR imaging in 23 patients with CADASIL at the initial stage of the disease (Mini-Mental State Examination score > 24 and modified Rankin scale score ≤ 1; mean age, 53.5 ± 11.1 years) and 30 age- and sex-matched controls.RESULTS:T1 contrast between gray matter and normal-appearing white matter was significantly reduced in patients compared with age- and sex-matched controls (patients: 1.35 ± 0.08 versus controls: 1.43 ± 0.04, P < 10⁻⁵). This reduction was mainly driven by a signal decrease in normal-appearing white matter. Contrast loss was strongly related to the volume of white matter hyperintensities.CONCLUSIONS:Conventional 3D T1 imaging shows significant loss of contrast between gray matter and normal-appearing white matter in CADASIL. This probably reflects tissue changes in normal-appearing white matter outside signal abnormalities on T2 or FLAIR sequences. These contrast alterations should be taken into account for image interpretation and postprocessing.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary small-vessel disease of the brain secondary to mutations of the NOTCH3 gene.¹ Conventional MR imaging markers have been repeatedly investigated in this disorder.^2–5 The impact of lacunar lesions detected on T1-weighted sequences seems more important than that of white matter lesions observed on FLAIR sequences.⁶ Recently, various measures of brain and cortical atrophy were shown to be related to clinical worsening.^7,8As reported in the context of Alzheimer disease,⁹ contrast between gray matter and normal-appearing white matter (NAWM) may be altered in CADASIL. This could have important implications for both image interpretation in the clinical setting and postprocessing in research studies. So far however, the alterations of MR imaging T1 contrast between GM and NAWM have not been evaluated in CADASIL. The aim of the present study was to assess potential contrast alterations between GM and NAWM on T1-weighted images in patients with CADASIL at the initial stage of the disease compared with age- and sex-matched individuals.     

单纯型遗传性痉挛性截瘫SPG6型中枢神经系统MRI表现

目的探讨单纯型遗传性痉挛性截瘫(purehereditary spastic paraplegia,PHSP)SPG6型患者的中枢神经系统MRI表现,提高对该病的认识。资料与方法分析一个家系6例PHSPSPG6型患者中枢神经系统的MRI表现,6例均行颅脑和脊髓MRI,分别测量C3、C7、T2、T4、T7脊椎水平脊髓前后径、横径和横断面积。另外选取60例在本院行颈椎和胸椎(各30例)MRI的患者作为对照组,测量方法同患者组,计算脊髓前后径、横径和横断面积的均值,并与患者组的均值进行比较。结果 6例中,5例颅脑MRI表现未见明显异常,1例表现为老年性脑改变;其颈髓及胸髓呈不同程度变细,灰白质均受累,蛛网膜下腔扩大;在变细明显的脊髓节段灰白质分界显示清楚,横轴位T2WI上灰质呈边界清楚、左右对称的点状或点片状高信号,矢状位上表现为连续纵行的条状高信号。6例患者的C3、C7、T2、T4脊椎水平的脊髓横断面积、前后径及横径明显小于对照组,二者之间的差异有统计学意义,T7脊椎水平的脊髓横断面积、前后径及横径与对照组之间的差异无统计学意义。结论 PHSPSPG6型患者的颅脑MRI表现可为正常。颈髓及上、中胸髓在MRI上表现...     

遗传性痉挛性截瘫并薄型胼胝体的MRI表现

目的探讨遗传性痉挛性截瘫(hereditary spastic paraplegia,HSP)伴薄型胼胝体的颅脑和脊髓MRI特征,以期提高对该病的认识。方法回顾性分析5个家系8例临床和遗传学确诊为HSP伴薄型胼胝体患者的颅脑和脊髓MRI资料。分析每例患者的MRI特点,并分别测量胼胝体膝部、体部和压部的厚度,分别在C3和T2水平测量相应平面脊髓的前后径及横径,另选取20例在本院行颅脑平扫MRI及颈椎MRI的正常病例为对照组进行相应测量方法进行比较。结果 8例颅脑MRI均表现为胼胝体变薄,以膝部和体部明显,分别为(2.2±1.6)mm、(2.0±0.9)mm,与正常对照组比较差异有统计学意义(P<0.05);胼胝体压部未见明显变薄(P>0.05);C3、T2脊髓的前后径、横径明显小于对照组(P<0.05)。8例均出现双侧脑室周围白质内及额顶叶深部脑白质对称性异常信号灶,液体衰减反转恢复序列(FLAIR)呈高信号。7例有脑萎缩,7例有颈胸段脊髓萎缩且其中1例胸髓末段显示异常信号灶。结论 HSP伴薄型胼胝体的颅脑和脊髓具有典型的MRI特点,主要表现为胼胝体膝部及体部变薄、脑萎缩、侧脑室周围脑白质内及额顶叶深部脑白质对称性异常信号灶及脊髓萎缩。MRI对临床诊断和鉴别诊断有重要意义,但确诊还需结合临床表现和基因检查。     

针刺对兔不完全性截瘫损伤脊髓bFGF免疫组化阳性表达的动态影响

目的：探讨针灸治疗不完全性截瘫对bFGF阳性表达的影响及其对脊髓损伤修复的意义。方法：采用不完全性截瘫兔模型,于伤后6 h、7 d、15 d取损伤脊髓组织3 mm长,用免疫组织化学S-P法染色,并用美国产Optimas6.51彩色图象分析系统进行图像分析。结果：造模后,bFGF表达主要在脊髓白质部位,并于第7 d开始针灸组脊髓白质灰质阳性颗粒表达明显下降,出现低谷,而模型组明显上升,第15 d均稍有恢复。结论：针灸作用于截瘫早期脊髓损伤的机理为对内源性bFGF的抑制,7 d时明显降低BFGF合成释放,达到抗瘢痕形成,抗粘连作用,从而减轻继发性损害有关,为脊髓功能恢复提供了有利条件。     

Relative Concentrations of Proton MR Visible Neurochemicals in Gray and White Matter in Human Brain

The relative distributions of N-acetylaspartate (NAA) + N-acetylaspartylglutamate (NAAG), creatine + phosphocreatine (Cr/PCr), and choline (Cho) in the gray and white matter of human brain were determined by utilizing proton magnetic resonance spectroscopic imaging (SI). The SI data was processed using an automated spectroscopic image processing algorithm, and image segmentation was performed using a supervised technique. Linear regression analysis indicated that the NAA + NAAG (2.01 ppm) and Cr/PCr (3.02 ppm) peaks are greater in gray matter compared with white matter. The large intersubject variation observed in the Cho (3.20 ppm) resonance prevented the assessment of its regional distribution with confidence.     

扩散加权成像在新生儿早期脑白质损伤的诊断价值

目的:探讨磁共振扩散加权成像(diffusion-weighted imaging,DWI)在新生儿早期脑白质损伤的诊断价值.方法:选取有明确围生期窒息史,日龄≤7天的早产儿缺氧缺血性脑损伤(HIBD)412例、足月新生儿缺氧缺血性脑病(HIE)566例作为研究对象,另随机选取日龄相同临床及颅脑MRI检查结果正常的156例早产儿、227例足月新生儿作为正常对照组,全部行颅脑常规MRI和DWI检查.分别测量DWI上研究组异常高信号区和正常对照组同一位置表观弥散系数(ADC值).将两组ADC值分别计算其平均值±标准差,组间数据分别进行t检验分析,P值小于0.05表明有统计学意义.结果:①412例HIBD中382例常规MRI显示脑室旁短T_1信号.156例DWI表现为脑室旁、内囊前后肢、胼胝体膝压部有异常高信号占37.86%,病灶呈局灶性分布74例,弥漫性分布82例,其中30例常规MRI未见异常但在DWI显示异常;566例HIE中,轻度267例、中度206例、重度93例.DWI上表现为皮质下深部白质异常高信号为227例,病变显示率为40.1%,异常高信号呈局灶性分布150例,弥漫性分布77例,其中18例在常规MRI未见异常.②DWI上,HIBD灶状病变和弥漫性病变平均ADC值分别为(0.976±0.041)×10-3mm2/s,(0.949±0.039)×10-3mm2/s;HIE灶状病变和弥漫性病变平均ADC值分别为(0.639±0.108)×10-3mm2/s,(0.626±0.112)×10-3mm2/s,研究组脑白质异常高信号区平均ADC值分别显著低于正常对照组同一部位,P<0.05,表明ADC值研究组与正常对照组组间存在差异.结论:常规MRI检查与DWI序列结合可显著提高新生儿脑白质损伤的早期诊断率,为临床早期准确诊断脑瘫、早期干预、评估预后及康复治疗奠定基础.     

脊髓损伤组织血小板活化因子变化与脊髓水肿的关系

采用改良的Ａｌｌｅｎ法打击猫脊髓致伤模型，测定伤后２小时－１周伤区及邻近脊髓组织血小板活化因子（ＰＡＦ）含量及水含量。结果表明，伤后２－７５小时伤区及邻近脊髓组织ＰＡＦ含量及水含量较对照组明显增高，而伤后１周时与对照组无显著性差异。提示ＰＡＦ在脊髓损伤后脊髓水肿的发生、发展过程中起重要作用。     

Gray, White Matter Concentration Changes and Their Correlation with Heterotopic Neurons in Temporal Lobe Epilepsy

Objective

To identify changes in gray and white matter concentrations (GMC, WMC), and their relation to heterotopic neuron numbers in mesial temporal lobe epilepsy (mTLE).

Materials and Methods

The gray matter or white matter concentrations of 16 left and 15 right mTLE patients who achieved an excellent surgical outcome were compared with those of 24 healthy volunteers for the left group and with 23 healthy volunteers for the right group, by optimized voxel-based morphometry using unmodulated and modulated images. A histologic count of heterotopic neurons was obtained in the white matter of the anterior temporal lobe originating from the patients'' surgical specimens. In addition, the number of heterotopic neurons were tested to determine if there was a correlation with the GMC or WMC.

Results

The GMCs of the left and right mTLE groups were reduced in the ipsilateral hippocampi, bilateral thalami, precentral gyri, and in the cerebellum. The WMCs were reduced in the ipsilateral white matter of the anterior temporal lobe, bilateral parahippocampal gyri, and internal capsules, but increased in the pons and bilateral precentral gyri. The heterotopic neuron counts in the left mTLE group showed a positive correlation (r = 0.819, p < 0.0001) with GMCs and a negative correlation (r = -0.839, p < 0.0001) with WMCs in the white matter of the anterior temporal lobe.

Conclusion

The present study shows the abnormalities of the cortico-thalamo-hippocampal network including a gray matter volume reduction in the anterior frontal lobes and an abnormality of brain tissue concentration in the pontine area. Furthermore, heterotopic neuron numbers were significantly correlated with GMC or WMC in the left white matter of anterior temporal lobe.     

酪氨酸受体激酶B在胚胎脊髓修复成鼠损伤脊髓过程中的变化

目的确定酪氨酸受体激酶Ｂ（ｔｒｋＢ）在胚胎脊髓修复成鼠脊髓损伤过程中的变化。方法将妊娠１４天胚胎脊髓植入急性损伤的成体脊髓后１，３，５，７，１０，１５和３０天，用原位杂交、斑点杂交和免疫组化技术对ｔｒｋＢｍＲＮＡ与蛋白作定性和定量观察。结果定性观察表明，在正常大鼠脊髓内，ｔｒｋＢｍＲＮＡ杂交产物主要分布在神经元和胶质细胞，神经纤维杂交反应不明显；脊髓损伤后阳性神经元和胶质细胞都有所增加，但阳性神经纤维增加的数目略为突出；胚胎脊髓植入损伤脊髓后，上述各阳性反应成分进一步增加，尤其是阳性神经纤维的增加更为显著。定量观察显示的ｔｒｋＢｍＲＮＡ的分子杂交反应与定性观察结果大体一致。免疫组化显色的ｔｒｋＢ蛋白，无论分布还是反应强度都与其ｍＲＮＡ的变化大致相符。结论损伤脊髓在移植修复过程中能够以调整受体合成的方式来适应营养环境的变化，但胶质细胞受体合成增加可能起了与神经成分争夺神经营养因子的副作用     

Acceleration of Normal-Tissue Damage Expression by Early Stimulation of Cell Proliferation in Rat Spinal Cord

PURPOSE: To examine experimental strategies for prevention of radiation-induced late spinal cord damage. MATERIAL AND METHODS: The effects of treatment with high, proliferation-stimulating doses of platelet-derived growth factor (PDGF) administered at various times after radiotherapy of rat spinal cord, and aiming at increased tissue regeneration, were studied in an established model. Animals were followed and monitored for expression of radiation myelopathy (RM), which was confirmed by histopathologic diagnosis. RESULTS: High doses of PDGF given 8 weeks after radiotherapy significantly accelerated the development of RM compared to control animals (Figure 1). Such effects were observed also for concomitant treatment, but not for PDGF administration after 12 or 15 weeks (Figure 2). On the microscopic level, the spinal cord showed more pronounced vascular damage with vessel necroses and hemorrhages (Figure 3). CONCLUSION: These data suggest that the vascular system plays an important role during development of RM and that early stimulation of cell proliferation negatively influences the time course of spinal cord damage. Further experiments should address different concepts of tissue regeneration or damage prevention.     

基于TBSS的急性CO中毒患者脑白质微细结构损伤研究

目的应用扩散张量成像(DTI)观察急性CO中毒患者脑白质结构的改变,应用影像技术量化脑白质损害程度,推测急性CO中毒迟发性脑病相关机制。方法对25例急性CO中毒患者和25例性别与年龄相匹配的健康志愿者进行头部磁共振DTI扫描,采用基于纤维束示踪的空间统计方法(TBSS),分析急性CO中毒患者脑白质平均扩散系数(MD)、各向异性分数(FA)的变化,探讨其与患者认知功能障碍间的相关性。结果与健康对照组对比,急性CO中毒患者组的放射冠、胼胝体的MD增高而FA降低(P<0.05);双侧上纵束,内、外囊,丘脑和脑干的MD增加但无FA改变(P<0.05)。与临床量表分数相关性比较发现,差异脑区FA值与MMSE评分呈一定正相关(P<0.05),差异脑区MD值与MMSE评分呈一定负相关(P<0.05)。结论DTI准确反映急性CO中毒导致脑内白质广泛的血管源性水肿以及脑白质纤维束完整性损害,可能量化反应病情缺氧脑损伤程度、预测迟发性脑病,同时DTI参数的改变还可以一定程度反映患者认知障碍情况。     

胚胎脊髓不同移植方法促进成鼠损伤脊髓功能恢复的研究

目的研究提供血运的胚胎脊髓移植对成鼠损伤脊髓功能恢复的作用。方法将胚胎脊髓组织、胚胎十大网膜组织、胚胎＋椎旁肌组织移植到成鼠半切洞损伤的脊髓中,手术后进行联合行为评分,感觉诱发电位,运动诱发电位检查。结果联合行为评分,单纯移植组和胚胎＋大网膜组织优于单纯损伤组,感觉诱发电位,运动诱发电位潜峰时的恢复,移植各组均优于单损伤组。胚胎＋大网膜组效果最好,单纯胚胎脊髓移植组优于胚胎＋椎旁肌移植组。结论通过各种功能检查表明提供血运的胚胎脊髓移植对成鼠损伤脊髓功能恢复有较好的促进作用。