Potential of diffusion tensor MR imaging in the assessment of cognitive impairments in children with periventricular leukomalacia born preterm

Purpose

To investigate MR diffusion tensor imaging (DTI) and fiber tractography (FT) in the assessment of altered major white matter fibers correlated with cognitive functions in preterm infants with periventricular leukomalacia (PVL), to explore the neural foundation for PVL children's cognitive impairments.

Materials and methods

Forty six preterm infants (16 ± 4.7 months) suffered from PVL and 16 age-matched normal controls were recruited. Developmental quotient (DQ) was recorded to evaluate PVL children's cognitive functions. According to the DQ scores, patients were divided into three groups: mild, moderate and severe cognitive impairment groups. DTI scan was performed. Fractional anisotropy (FA) values of major white matter fibers were measured and their correlation with cognitive levels was evaluated.

Results

Compared with the control group, the PVL group showed a significant mean FA reduction in bilateral corticospinal tract (CST), anterior/posterior limb of internal capsule (ICAL/ICPL), arcuate fasciculus (AF), corona radiate (CR), superior longitudinal fasciculus (SLF), splenium of corpus callosum (SCC) (p < 0.05) and bilateral posterior thalamic radiation (PTR) (p < 0.01). The FA values of left CST, bilateral AF, anterior cingulum (ACG), SLF, ICAL, ICPL, PTR, CR, genu of corpus callosum (GCC), SCC and middle cerebellar peduncle showed significant negative correlations with the cognitive levels.

Conclusions

DTI can provide more information for understanding the pathophysiology of cognitive impairment in preterm infants with PVL.     

MR扩散张量成像评价脑室旁白质软化症脑性瘫痪患儿认知功能的研究

目的 探讨MR DTI及白质纤维束成像(FT)在评价脑室旁白质软化症(PVL)脑性瘫痪患儿认知功能中的应用价值,为揭示PVL患儿认知功能障碍的可能神经基础提供帮助.方法 选取46例临床确诊为脑性瘫痪的PVL患儿,同时选择足月无窒息史的健康儿童16名进行对照研究.应用发育商(DQ)评价患儿认知功能,根据DQ值将患儿分为轻(11例)、中(19例)、重度(16例)认知障碍组.对受试儿童进行常规MRI及DTI检查,计算各组患儿主要白质纤维束各向异性分数(FA)值,患儿组与对照组间进行非配对t检验,各认知障碍组及对照组组间比较采用单因素方差分析.结果 与对照组相比,患儿组左侧皮质脊髓束(患儿组:0.476 ±0.064;对照组:0.531±0.064),双侧内囊前肢(患儿组:左侧0.357±0.050,右侧0.370±0.040;对照组:左侧0.405±0.081,右侧0.405±0.036),双侧内囊后肢(患儿组:左侧0.483±0.044,右侧0.485±0.046;对照组:左侧0.546±0.091,右侧0.547±0.083),双侧弓状束(患儿组:左侧0.367±0.069,右侧0.363±0.064;对照组:左侧0.433±0.097,右侧0.421±0.091),双侧丘脑后辐射(患儿组:左侧0.390±0.059,右侧0.382±0.047;对照组:左侧0.459±0.067,右侧0.446±0.064),双侧前扣带束(患儿组:左侧0.362±0.056,右侧0.345±0.056;对照组:左侧0.423±0.057,右侧0.417±0.080),双侧上纵束(患儿组:左侧0.323±0.050,右侧0.341±0.056;对照组:左侧0.426±0.102,右侧0.416±0.092)及胼胝体压部(患儿组:0.535±0.090;对照组:0.606±0.060)的FA值显著减低,差异有统计学意义(t值为2.037 ～3.745,P值均＜0.05);随认知障碍程度的加重,所有纤维束的FA值逐渐下降,各认知障碍组及对照组进行组间比较发现双侧皮质脊髓束、内囊前肢、内囊后肢、左侧弓状束、双侧丘脑后辐射、前扣带束、上纵束及胼胝体压部的FA值差异有统计学意义(F值为3.021 ～7.146,P值均＜0.05).进一步两两比较显示,以上纤维束的FA值在对照组与重度认知障碍组间比较,差异均有统计学意义(P值均＜0.05).结论 PVL患儿认知功能障碍与脑内广泛白质纤维束损伤有关,DTI及FT在评价PVL患儿认知功能方面有较高的应用价值.     

儿童脑室周围白质软化症的临床和MRI诊断

目的探讨儿童脑室周围白质软化症（ＰＶＬ）的ＭＲ征象及与临床表现的关系。方法回顾性分析１５例ＰＶＬ的临床资料和ＭＲ表现。结果（１）脑白质减少单纯在三角部周围９例，三角部和半卵圆中心３例，体部周围１例。（２）Ｔ２ＷＩ白质内高信号在侧脑室额角、体部和三角部周围的白质中，仅１个部位者５例，２个部位者５例，三个部位同时受累者５例。另４例伴有小的软化灶和囊变区。（３）７例有侧脑室扩大，４例伴有侧脑室形态不规则。（４）８例显示双侧外侧裂加深增宽。（５）５例出现胼胝体异常。（６）根据ＭＲ征象，将ＰＶＬ分为轻、中和重度３度，本组属于轻、中、重度者各５例。结论ＭＲ可清楚显示ＰＶＬ的病变程度和范围，水抑制序列显示病变更清楚，临床表现与ＭＲ所示病变侵犯范围密切相关     

儿童脑室周围白质软化症的MR扩散张量成像研究

目的应用MR扩散张量成像对脑室周围白质软化症(PVL)患儿和正常婴幼儿进行比较。方法对15例正常志愿者和15例PVL患儿进行了扩散张量成像扫描,测量双侧内囊后肢、双侧视放射和胼胝体膝部、压部的部分各向异性(FA)值,并对结果进行统计学比较。结果对照组和PVL组的右侧内囊后肢的FA值分别为0682±0399和0555±0087、左侧内囊后肢的FA值分别为0673±0043和0557±0030,右侧和左侧视放射的FA值分别为0437±0675、0429±0052、0351±0051、0339±0064,胼胝体膝部、压部的FA值分别为0696±0579、0756±0454、0564±0080、0586±0100,差异均有统计学意义(P<001)。结论扩散张量成像能提示纤维束的髓鞘化过程的延迟,反映儿童发育中脑白质微观结构的改变,在PVL的随访观察中具有较大的潜力。     

儿童脑室周围白质软化症的MRI诊断

儿童脑室周围白质软化症(periventricular leukomalacia,PVL),是缺血缺氧导致的脑白质损伤的严重并发症.本文回顾性分析16例PVL患者的临床资料与MRI表现,旨在加深对本病的认识,提高本病的诊断符合率。1材料与方法1.1一般资料收集2005年7月～2011年12月经我院MR检查并经临床确诊的PVL患儿16例,其中男9例,女7例,年龄5个     

小儿脑室周围白质软化症的临床特征和MRI表现

目的 探讨小儿侧脑室周围白质软化症(PVL)的临床特点与MRI影像学表现.方法 对14例PVL的临床资料及磁共振表现进行回顾性分析.结果 PVL的MRI表现包括脑室旁软化灶形成(10例)、侧脑室变形(9例)、脑白质减少(7例)、脑沟及脑裂加深(6例)等,软化灶分布在侧脑室周围及半卵圆中心区,形态大小不一,为长T1、长T2信号、flair为低信号;临床表现为:发育迟缓(6例)、癫痫(7例)、肢体功能障碍(6例)、视力损害(1例)等,7例患儿有缺血缺氧病史.结论 PVL的影像学表现具有一定特征性,MRI是诊断PVL的主要方法.     

儿童脑室周围白质软化症的MRI与临床对比研究

目的 分析儿童脑室周围白质软化症(PVL)的MRI表现与妊娠时间与临床症状的关系。方法 搜集34例有晚期PVL典型表现的病例，按早产组及足月组分析其MRI改变，包括脑室周围异常高信号、皮质或皮层下白质的损伤和脑白质减少程度与相应的临床症状。结果 (1)早产组T2WI脑室周围高信号程度较足月组重，Z值为3．840，P值为0．000；(2)19例足月组PVL中9例有皮质或皮层下白质的损伤，而早产儿仅占1／15，P值为0．020；(3)足月组有抽搐表现者较早产组多见，P=0．036；(4)两组的运动障碍和智力落后均与脑白质减少严重程度相关，运动障碍Z=-3．047，P：0．002；智力落后Z=-3．786，P=0．000，智力落后与胼胝体发育不良有关(Z==2．499，P=0．012)．早产组视力异常与脑白质减少相关。结论 MRI可清楚显示PVL的病变程度及范围，PVL患者的妊娠时间和临床症状与MRI所示的改变密切相关。     

Abnormal venous drainage in periventricular leukomalacia

Age-matched six control subjects and 14 selected paediatric patients with periventricular leukomalacia were prospectively studied by MR imaging, and MR angiography. MR angiograms were acquired utilizing either the three-dimensional phase-contrast (3D-PC) or the two-dimensional time-of-flight (2D-TOF) techniques, or both, in an axial slab centred to the centrum semiovale. Abnormal draining veins (slightly enlarged and long vessels with abnormal courses) were found in eight of 14 patients (57%). In five of these eight patients (62.5%) abnormal vessels were identified on conventional MR imaging (spin-echo, T2-weighted and flow sensitive images), while the 3D-PC or 2D-TOF angiograms demonstrated the abnormal vessels in all the patients (100%). Usually there was a single abnormal vessel at the region of interest. These vessels should not be misinterpreted as arteriovenous malformations or venous malformations.     

MR imaging of periventricular leukomalacia in childhood

Eight children with clinical and radiologic abnormalities consistent with periventricular leukomalacia were investigated with MR imaging of the brain that employed both inversion-recovery and T2-weighted spin-echo imaging sequences. The more precise delineation of white and gray matter on inversion-recovery images as compared with CT allows a detailed demonstration of the anatomic features of periventricular leukomalacia; specifically, a reduced quantity of white matter in the periventricular region and centrum semiovale and, in more severe cases, cavitated infarcts that replace the immediate periventricular white matter. The T2-weighted spin-echo and short inversion time inversion-recovery images demonstrated abnormally increased signal in white matter that appeared normal on CT scans and only minimally abnormal on conventional inversion-recovery images. These abnormalities most probably represent white matter gliosis that extends beyond the immediate periventricular regions. MR recognition of cerebral white matter abnormalities associated with periventricular leukomalacia may confirm the clinical suspicion of this diagnosis in children with spastic diplegia or quadriplegia.     

Diffusion tensor imaging in children with periventricular leukomalacia: variability of injuries to white matter tracts

BACKGROUND AND PURPOSE: Conventional MR imaging shows evidence of brain injury and/or maldevelopment in 70%-90% of children with cerebral palsy (CP), though its capability to identify specific white matter tract injury is limited. The great variability of white matter lesions in CP already demonstrated by postmortem studies is thought to be one of the reasons why response to treatment is so variable. Our hypothesis is that diffusion tensor imaging (DTI) is a suitable technique to provide in vivo characterization of specific white matter tract lesions in children with CP associated with periventricular leukomalacia (PVL). MATERIALS AND METHODS: In this study, 24 children with CP associated with PVL and 35 healthy controls were evaluated with DTI. Criteria for identification of 26 white matter tracts on the basis of 2D DTI color-coded maps were established, and a qualitative scoring system, based on visual inspection of the tracts in comparison with age-matched controls, was used to grade the severity of abnormalities. An ordinal grading system (0=normal, 1=abnormal, 2=severely abnormal or absent) was used to score each white matter tract. RESULTS: There was marked variability in white matter injury pattern in patients with PVL, with the most frequent injury to the retrolenticular part of the internal capsule, posterior thalamic radiation, superior corona radiata, and commissural fibers. CONCLUSION: DTI is a suitable technique for in vivo assessment of specific white matter lesions in patients with PVL and, thus, a potentially valuable diagnostic tool. The tract-specific evaluation revealed a family of tracts that are highly susceptible in PVL, important information that can potentially be used to tailor treatment options in the future.     

儿童脑室周围白质软化症的CT诊断

目的探讨儿童脑室周围白质软化症(PVL)的CT表现,提高CT诊断的准确性。方法回顾性分析126例儿童脑室周围白质软化症的临床及CT表现。结果CT显示所有患儿均有不同程度的脑白质减少,单纯三角区周围减少10例,普遍减少者116例。侧脑室无明显增大13例;局部增大73例,其中,单纯三角区扩大者6例,三角区及体部扩大者63例,前角及体部扩大者4例;普遍增大40例:侧脑室外侧缘不规则者41例。局部皮质脑回、脑沟向中线结构延伸移位52例。侧脑室周围见斑点状、裂隙样低密度灶61例。大脑皮质萎缩、胼胝体发育不良和小头畸形分别为23、15和15例。结论儿童PVL的CT表现具有特征性,结合临床,CT能够做出正确的诊断。     

Non-invasive assessment of axonal fiber connectivity in the human brain via diffusion tensor MRI.

A technique for assessing in vivo fiber connectivity in the human brain is presented. The method utilizes a novel connectivity algorithm that operates in three spatial dimensions and uses estimates of fiber tract orientation and tissue anisotropy, obtained from diffusion tensor magnetic resonance imaging, to establish the pathways of fiber tracts. Sample in vivo connectivity images from healthy human brain are presented that demonstrate connections in the white matter tracts. White matter connectivity information is potentially of interest in the study of a range of neurological, psychiatric, and developmental disorders and shows promise for following the natural history of disease.     

Pontine hypoplasia in children with periventricular leukomalacia

BACKGROUND AND PURPOSE: The brain stem in patients with periventricular leukomalacia (PVL) appears smaller than normal on MR imaging, but few reports have described this feature, and the number of patients has been relatively small. The present study was conducted to examine the hypothesis that the pons in patients with PVL is smaller than normal.MATERIALS AND METHODS: Using MR imaging, we examined 80 children (43 boys and 37 girls) with PVL and 80 age-matched control children (41 boys and 39 girls). The control children were diagnosed as neurologically and developmentally normal by pediatric neurologists and also showed normal MR imaging findings. MR imaging was performed at a corrected age range of 0–5 years in both groups. We measured the anteroposterior diameter of the whole pons, the tegmentum and the basis, and the corpus callosal length by using midline T1-weighted sagittal images and compared each parameter between the PVL groups and the control groups.RESULTS: Pontine diameters in all of the regions were significantly smaller in the PVL group than in the control group (mean ± SD, whole pontine diameters, 1.66 ± 0.21 and 1.87 ± 0.23 cm [P < .001]; basis diameters, 0.42 ± 0.10 and 0.51 ± 0.14 [P < .001]; tegmentum diameters, 1.23 ± 0.20 and 1.36 ± 0.19 [P < .001], respectively). The respective corpus callosal lengths were 5.02 ± 0.90 and 5.51 ± 0.76 (P < .001). There was no significant difference in the basis/tegmentum ratio between the PVL group and the control group. When the age-related pontine diameter differences were examined, there was already a significant difference at 0 years of age between the 2 groups. There was a significant correlation between whole pontine diameter and corpus callosal length in the PVL group (correlation coefficient, 0.52; P < .001) and the control group (correlation coefficient, 0.63; P < .001).CONCLUSION: We have proven that pontine diameter in patients with PVL is significantly smaller than that in normal control subjects, including each diameter of basis and tegmentum.

Periventricular white matter injury, that is, periventricular leukomalacia (PVL), is the dominant form of brain injury in premature infants that is later manifested as spastic cerebral palsy (spastic diplegia and spastic quadriplegia), with cognitive impairment and seizures in some children.¹ The pathogenesis of this lesion is considered to be related to ischemia of the white matter, infection, hypotension, and hypocarbia or a combination of these factors.² PVL consists of 2 components, that is, focal necrosis with loss of all cellular elements deep in the periventricular white matter and diffuse white matter involvement due to injury to glial cells, presumed to be oligodendroglia progenitors (preoligodendroglia).² On MR imaging, the characteristic findings of PVL include volume loss of the white matter, associated with ventriculomegaly with irregular margin, cystic change, periventricular hyperintensity on T2-weighted images, and a thin corpus callosum.^3,4 These are the results of white matter cavitation, loss, and gliosis.⁵Although PVL is a form of deep white matter injury leading to loss of periventricular and deep white matter volume,² its relationship to the development of white matter tracts is still unclear. A neuropathologic study has reported that the PVL lesions (spongy change with astrogliosis) in extremely low birth weight infants affect fibers involved in motor, sensory, visual, and higher cerebral function, predominantly in the descending corticospinal tract and in the thalamocortical tract, that is, descending motor tracts.⁵ On the other hand, a study using tractography has shown that the fibers connected to the sensory cortex are markedly reduced in comparison with the corticospinal tract in some patients with severe PVL.⁶ Recently, Nagae et al⁷ reported that the sensory fibers were affected in PVL patients more severely than motor fibers by using diffusion tensor imaging (DTI) of 24 children diagnosed with cerebral palsy.In the brain stem, motor tracts descend through the ventral site, and sensory tracts ascend through the dorsal site.^8,9 On conventional MR imaging, the brain stem in patients with PVL appears smaller than normal. With regard to the size of the whole pons on MR imaging, however, only one article has demonstrated a smaller pontine diameter in PVL children, and the number of patients that they examined was relatively small.¹⁰ The purpose of the present study is to examine the hypothesis that the pons in patients with PVL is smaller than in normal control subjects by using a larger series.     

Intercenter differences in diffusion tensor MRI acquisition

Purpose:

To assess the effect on diffusion tensor (DT) magnetic resonance imaging (MRI) of acquiring data with different scanners.

Materials and Methods:

Forty‐four healthy controls and 36 multiple sclerosis patients with low disability were studied using eight MR scanners with acquisition protocols that were as close to a standard protocol as possible. Between 7 and 13 subjects were studied in each center. Region‐of‐interest (ROI) and histogram‐based analyses of fractional anisotropy (FA), axial (D_ax), radial (D_rad), and mean diffusivity (MD) were performed. The influence of variables such as the acquisition center and the control/patient group was determined with an analysis of variance (ANOVA) test.

Results:

The patient/control group explained ≈25% of data variability of FA and D_rad from midsagittal corpus callosum (CC) ROIs. Global FA, MD, and D_rad in the white matter differentiated patients from controls, but with lower discriminatory power than for the CC. In the gray matter, MD discriminated patients from controls (30% of variability explained by group vs. 17% by center).

Conclusion:

Significant variability of DT‐MRI data can be attributed to the acquisition center, even when a standardized protocol is used. The use of appropriate segmentation methods and statistical models allows DT‐derived metrics to differentiate patients from healthy controls. J. Magn. Reson. Imaging 2010;31:1458–1468. © 2010 Wiley‐Liss, Inc.     

Radiological diagnosis of periventricular and subcortical leukomalacia

Summary Nine newborn infants with histories of perinatal asphyxia are presented. The pneumoencephalographic findings which led to the diagnosis are typical and constant. They include marked subcortical atrophy with rounded, dilated, and undisplaced lateral ventricles. Cystography with 3 cc of air demonstrated multiple subcortical and pareventricular cavities, without communication with the ventricular system, but with the typical honeycomb appearance of paraventricular and subcortical leukomalacia described in postmortem findings. The CT findings are typical, and provide the location of the cavities as well as their density.     

Usefulness and limitations of neuroradiologic tests (CT, US, MRI) in periventricular leukomalacia

Sixteen young patients, with clinical and radiological signs of periventricular leukomalacia (PVL), were investigated with MR imaging. Twelve of them were investigated with US in the perinatal period. The extant 4 patients, older than the others, had a clinical history of PVL. US scans were capable of yielding precise information about the anatomical features of PVL in both the acute and the middle phases. The lesions appeared as hyperechoic areas which subsequently turned to anechoic cavities. MR imaging and CT scans did not present any particular advantage over US scans in the acute phase, but they did detect periventricular damage when the patient was 6-7 months old. MR imaging was superior to CT in detecting the delayed myelination of white matter. Inversion-recovery sequences gave more anatomical details to distinguish normal from abnormal white matter. Spin-echo proton-density images detected periventricular gliosis, which appeared as persistent hyperintense areas. CT might be useful in the acute phase, after US detection of hyperechoic intraparenchymal areas, for it allowed purely ischemic lesions to be distinguished from hemorrhagic ones.     

Characterizing fiber directional uncertainty in diffusion tensor MRI

Image noise in diffusion tensor MRI (DT‐MRI) causes errors in the measured tensor and hence variance in the estimated fiber orientation. Uncertainty in fiber orientation has been described using a circular “cone of uncertainty” (CU) around the principal eigenvector of the DT. The CU has proved to be a useful construct for quantifying and visualizing the variability of DT‐MRI parameters and fiber tractography. The assumption of circularity of the CU has not been tested directly, however. In this work, bootstrap analysis and simple theoretical arguments were used to show that the CU is elliptical and multivariate normal in the vast majority of white matter (WM) voxels for typical measurement conditions. The dependence of the cone angle on the signal‐to‐noise ratio (SNR) and eigenvalue contrast was established. The major and minor cone axes are shown to be coincident with the second and third eigenvectors of the tensor, respectively, in the limit of many uniformly spaced diffusion‐encoding directions. The deviation between the major cone axis and the second eigenvector was quantified for typical sets of diffusion‐weighting (DW) directions. The elliptical CU provides more realistic error information for fiber‐tracking algorithms and a quantitative basis for selecting DT imaging acquisition protocols. Magn Reson Med 60:1408–1421, 2008. © 2008 Wiley‐Liss, Inc.     

Diffusion-weighted MR imaging in the early diagnosis of periventricular leukomalacia

Diffusion-weighted imaging (DWI) has been shown to be highly sensitive in detecting acute cerebral infarction, but its use in detecting hypoxic–ischemic encephalopathy (HIE) in neonates is still controversial. Moreover, few reports concern pre-term infants with possible periventricular leukomalacia (PVL). We examined the ability of this technique to detect cerebral changes in the acute phase of PVL. Fifteen MR examinations were performed in 11 pre-term infants (mean age 3.4 days, range 2–6 days). Conventional DWI sequences, apparent diffusion coefficient (ADC) maps, and US obtained in the acute phase were compared. All the neonates underwent US follow-up up to 4 months after delivery; those with suspected PVL also underwent MRI follow-up for up to 2 months. Qualitative and quantitative evaluations were performed to assess the presence of DW changes compatible with PVL. Diffusion-weighted MRI showed signal hyperintensity associated with decreased ADC values in 3 subjects (27%). In these patients conventional MRI sequences were interpreted as normal and US (performed at the same time) as doubtful in 2 and compatible with PVL in 1 subject. The MRI and US follow-up confirmed severe damage in all these patients. In 1 neonate hemorrhages involving the germinative matrix were identified. In 8 neonates MRI was considered normal. In these subjects US follow-up (up to 4 months) confirmed no signs of PVL. Diffusion-weighted imaging may have a higher correlation with later evidence of PVL than does conventional MR imaging and US when performed in the acute phase of the disease.     

MRI及MR扩散张量成像对肌萎缩侧索硬化症的初步评价

目的　描述肌萎缩侧索硬化症 (ALS)的脑部MR影像学表现特点 ,探讨常规MR成像及MR扩散张量成像 (DTI)部分各向异性 (FA)值在本病诊断中的价值。方法　对 14例临床确诊的ALS患者和 12例正常人行MR扫描 ,其中 2例患者行增强扫描。对 10例患者及 12例正常人行DTI横轴面和冠状面扫描 ,使用自旋回波 回波平面成像 (SE EPI)序列 ,b值为 10 0 0s/mm2 ,扩散敏感梯度方向为 2 5。为定量评价锥体束 ,在内囊后肢和中脑大脑脚水平测量双侧锥体束的FA值并做统计学处理。结果　 6例患者双侧内囊后肢呈局限性T1WI略低信号及T2 WI高信号 (高于皮层信号 ) ,冠状面T2 WI可明确显示内囊后肢至大脑脚纵向连续的带状高信号影 ,符合锥体束走行 ;8例患者双侧内囊后肢呈局限性T1WI略低信号及T2 WI略高信号 (与皮层信号相等 )。 2例行增强扫描者均未见异常对比增强。 12例正常人双侧内囊后肢均呈局限性T1WI略低信号及T2 WI略高信号 (与皮层信号相等 )。病变组FA值在内囊后肢水平和中脑大脑脚水平均明显低于对照组FA值 (F =7.38,P <0 .0 1;F =7.31,P =0 .0 1)。结论　常规MR成像诊断ALS时须结合临床资料。ALS患者锥体束区域FA值的下降提示存在神经元变性及继发性脱髓鞘 ,DTI可以在活体无创性地对锥体束及其潜在病变进行检测和评价