White matter fiber tractography and color mapping of the normal human cerebellum with diffusion tensor imaging

Diffusion tensor imaging (DTI) color mapping and fiber tractography was used to study the white matter within the cerebellum along with the afferent and efferent tracts associated with the cerebellum in 24 normal human subjects. The most prominent structures that can be readily identified using these DTI techniques are the middle, inferior and superior cerebellar peduncles. Furthermore DTI shows transverse white matter fiber that cross between the two cerebellar hemispheres at the level of the vermis. At the hemispheric level fibers to the dentate, to the emboliform nuclei are clearly visible on DTI as is the afferent pathway represented by the middle cerebellar peduncle. Selective DTI fiber tractography provides very exquisite images of the cerebellar peduncles and of the fibers projecting to and from the cerebellar cortex. This study demonstrates that DTI is complementary to conventional MRI in that DTI elucidates the orientation of white matter fiber bundles that are associated with the cerebellum. Therefore we anticipate that DTI will become an important adjunct to conventional MRI for clinical and basic studies of cerebellar ataxias and congenital disorders involving the cerebellum and brain stem. This work provides a summary of the normal DTI appearance of the cerebellar white matter which will be useful for interpreting DTI results in clinical populations.     

Demonstration of Recovery of a Patient with a Cerebellar Peduncle Injury due to Intracerebral Hemorrhage: a Diffusion Tensor Imaging Study.

背景：扩散张量成像可以对小脑脚进行三维显影。 目的：采用扩散张量成像,观察一位由于颅内出血所致小脑脚损伤患者在三个月内的功能恢复。 设计,时间和地点：病例研究,2008年10月至2009年3月期间在岭南大学医学院理疗康复教研室进行。 受试者：一位72岁女性患者,九名对照者,对照者同患者的年龄和性别相符。 方法：采用1.5T敏感性编码头线圈进行扩散张量成像。 主要观察指标：采用DTI-Studio软件评价小脑脚,包括小脑上脚,小脑中脚和小脑下脚。 结果：患者在发病三周后不能平坐,但可以独立行走,发病后4周可以完成大部分日常活动。3周扩散张量成像显示,所有小脑脚被血肿压迫。左小脑脚的后侧缩短,尤其是左小脑中脚在中部阻断。4月扩散张量成像显示,所有被压缩的小脑脚复原。此外,3周扩散张量成像结果还显示,除去右小脑中脚之外,所有小脑脚的各项异性值同正常对照值相比,降低了2个标准差。4月扩散张量成像结果显示,右小脑小脚的各项异性值有所增加,比正常对照值高出2个标准差。尽管如此,其他小脑脚的各项异性值仍保持在正常对照值之下的2个标准差。结果显示,发病后3周时的小脑脚的神经元损伤（所有小脑上脚,左小脑中脚和所有小脑下脚）在发病后4月内康复不明显。 结论：患者的功能性恢复最初是由于被压迫的小脑脚的减压所致,而不是受伤小脑脚的恢复。笔者认为采用扩散张量成像评价小脑脚对小脚损伤的疑似病例有帮助。     

Characterization and diagnostic potential of diffusion tractography in multiple system atrophy

IntroductionMicrostructural integrity of the middle cerebellar peduncle (MCP) and the putamen captured by diffusion-tensor imaging (DTI) is differentially affected in the parkinsonian and cerebellar variants of multiple system atrophy (MSA-P, MSA-C) compared to Parkinson's disease (PD). The current study applied DTI and tractography in order to 1) characterize the distribution of DTI metrics along the tracts of the MCP and from the putamen in MSA variants, and 2) evaluate the usefulness of combining these measures for the differential diagnosis of MSA-P against PD in the clinical setting.MethodsTwenty-nine MSA patients (MSA-C, n = 10; MSA-P, n = 19), with a mean disease duration of 2.8 ± 1.7 years, 19 PD patients, and 27 healthy controls (HC) were included in the study. Automatized tractography with a masking procedure was employed to isolate the MCP tracts. DTI measures along the tracts of the MCP and within the putamen were acquired and jointly used to classify MSA vs. PD, and MSA-P vs. PD. Putamen volume was additionally tested as classification feature in post hoc analyses.ResultsDTI measures within the MCP and putamen showed significant alterations in MSA variants compared to HC and PD. Classification accuracy for MSA vs. PD and MSA-P vs PD using diffusion measures was 91.7% and 89.5%, respectively. When replacing the putaminal DTI measure by a normalized measure of putamen volume classification accuracy improved to 95.8% and 94.7%, respectively.ConclusionMultimodal information from MCP tractography and putamen volume yields excellent diagnostic accuracy to discriminate between early-to-moderately advanced patients with MSA and PD.     

Diffusion tensor MRI and fiber tractography of cerebellar atrophy in phenytoin users

PURPOSE: The usefulness of diffusion tensor magnetic resonance imaging (DT-MRI) is still in debate, and the development of clinically feasible scan protocol is encouraged. The purpose of this study was to investigate the afferent fiber system to the cerebellum in patients with phenytoin (PHT)-induced cerebellar atrophy in comparison with cerebellar atrophy of other etiologies by using DT-MRI. METHODS: Thirteen patients (M/F ratio, 7:6; mean age, 42.5 years) and age-matched normal controls (n = 8) participated in this study. The patient group consisted of epilepsy patients who had received PHT therapy (n = 9) and clinically diagnosed as having olivopontocerebellar atrophy (OPCA; n = 4). DT-MRI was performed by using diffusion weighting of b = 600 s/mm2, and fractional anisotropy (FA) and color-coded vector maps were generated. FA of the middle cerebellar peduncle (MCP), the cerebellum, and transverse pontine fibers (TPF) was measured and compared between PHT and OPCA patients. RESULTS: Normal subjects showed FA values of 0.81 +/- 0.07 in MCP, 0.69 +/- 0.04 in TPF, and PHT users showed FA values of 0.84 +/- 0.09 in MCP, 0.72 +/- 0.08 in TPF, and 0.21 +/- 0.04 in cerebellum. OPCA patients showed FA values of 0.39 +/- 0.11 in MCP, 0.46 +/- 0.12 in TPF, and 0.22 +/- 0.07 in cerebellum. PHT users showed a statistically significant reduction of FA only in cerebellum, whereas OPCA demonstrated significant decrease of FA in MCP, TPF, and cerebellum (one-way analysis of variance, p < 0.01). Three-dimensional reconstruction of fiber tracts demonstrated decreased volume and altered fiber integrity within the peduncles and transverse pontine fibers in the OPCA group, whereas fiber course patterns in PHT users were similar to those in controls. CONCLUSIONS: PHT users showed normal orientation and anisotropy of MCP and TPF, whereas OPCA demonstrated impaired values, suggesting that PHT directly affects the cerebellum. DT-MRI can demonstrate detailed fiber configurations in degenerative diseases of brainstem and cerebellum and provides insight into the pathomechanisms of cerebellar atrophy.     

Delayed neural degeneration following gamma knife radiosurgery in a patient with an arteriovenous malformation: A diffusion tensor imaging study

Gamma knife surgery (GKS) is a proven modality for the treatment of arteriovenous malformations (AVMs), but neural degeneration is a serious complication of GKS. In this study, we report on a patient who displayed delayed neural degeneration following GKR, using diffusion tensor imaging (DTI). A 43-year-old male patient was diagnosed with an intraventricular hemorrhage (IVH) due to rupture of an AVM in the right middle cerebellar peduncle, and exhibited cognitive impairment, quadriparesis, and ataxia after IVH onset. He underwent GKS 5 weeks after onset. Brain MRIs performed at 6 weeks, 7 months, and 21 months post-onset revealed encephalomalactic lesions in the right pons, middle cerebellar peduncle, and medulla oblongata. DTI at 6 weeks post-onset suggested neural injuries of the right corticospinal tract (CST), right middle cerebellar peduncle (MCP), and right inferior cerebellar peduncle (ICP). DTI at 7 months suggested that the right CST and right ICP had recovered to some extent, which concurred with improved clinical manifestations. However, at 21 months, four neural tracts (right CST, right MCP, and both ICPs) appeared to have degenerated, which was in-line with aggravation of corresponding clinical manifestations. Experiences of this patient suggest DTI is a useful technique for the detection of neural degeneration after GKS.     

Reduced Anisotropy in the Middle Cerebellar Peduncle in Chiari-II Malformation

Besides supratentorial abnormalities, spina bifida menigomyelocele (SBM) is typically associated with Chiari-II malformation comprising a small cerebellum, which herniates downward due to a shallow posterior fossa. We used diffusion tensor imaging to probe additional microstructural alterations of the major cerebellar white matter tracts, the cerebellar peduncles. A region-of-interest approach was employed in six SBM patients and six matched controls to compare the fractional anisotropy (FA) within the superior, middle, and inferior cerebellar peduncle (SCP, MCP, and ICP, respectively). The FA in the MCP was significantly reduced in the SBM patients (0.44 vs. 0.65, p = 0.002), while there was no significant difference in the other cerebellar peduncles. In the context of numerous supratentorial white matter abnormalities in SBM such as callosal dysplasia, the most likely explanation of reduced FA in the MCP is a reduced fiber density.     

Posterior fossa decompression and the cerebellum in Chiari type II malformation: a preliminary MRI study

Objectives  

Chiari type II malformation (CII) is a congenital deformity of the hindbrain. The posterior fossa and cerebellum are small in CII. The cerebellar atrophy is associated with cognitive and motor deficits. Brainstem compression occurs in some patients with CII for whom posterior fossa decompression may be life saving. The aim was to determine whether posterior fossa decompression can prevent or reduce the cerebellar atrophy in CII.     

Undecussated Superior Cerebellar Peduncles and Absence of the Dorsal Transverse Pontine Fibers: a New Axonal Guidance Disorder?

Axonal guidance disorders are a newly recognized group of diseases of the human central nervous system. These disorders are characterized by white matter tracts with abnormal course and failure to cross the midline or presence of ectopic white matter tracts. Diffusion tensor imaging (DTI) and fiber tractography are suitable neuroimaging tools to detect morphological abnormalities in the course, decussation, and location of white matter tracts. We report on a 6.5-year-old child with significant global developmental delay. Axial color-coded fractional anisotropy (FA)-maps revealed absence of (1) the midline “focal red dot” at the level of the pontomesencephalic junction representing absence of decussation of the superior cerebellar peduncles and (2) the dorsal component of the transverse pontine fibers. These findings are highly suggestive of an axonal guidance disorders. The complete neuroimaging phenotype of this child does not match well-known diseases with similar DTI findings. We show how DTI reveals important information of microstructural brain malformations that may go undetected or remains underestimated and consequently DTI may suggest the possible pathomechanism. We conclude that this child may be suffering from a not yet described subtype of an axonal guidance disorder.     

Changes in a cerebellar peduncle lesion in a patient with Dandy-Walker malformation A diffusion tensor imaging study

We report a patient with severe ataxia due to Dandy-Walker malformation, who showed functional recovery over 10 months corresponding to a change in a cerebellar peduncle lesion. A 20-month-old female patient who was diagnosed with Dandy-Walker syndrome and six age- and sex-matched healthy control subjects were enrolled. The superior cerebellar peduncle, the middle cerebellar peduncle, and the inferior cerebellar peduncle were evaluated using fractional anisotropy and the apparent diffusion coefficient. The patients’ functional ambulation category was 0 at the initial visit, but improved to 2 at the follow-up evaluation, and Berg’s balance scale score also improved from 0 to 7. Initial diffusion tensor tractography revealed that the inferior cerebellar peduncle was not detected, that the fractional anisotropy of the superior cerebellar peduncle and middle cerebellar peduncle decreased by two standard deviations below, and that the apparent diffusion coefficient increased by two standard deviations over normal control values. However, on follow-up diffusion tensor tractography, both inferior cerebellar peduncles could be detected, and the fractional anisotropy of superior cerebellar peduncle increased to within two standard deviations of normal controls. The functional improvement in this patient appeared to correspond to changes in these cerebellar peduncles. We believe that evaluating cerebellar peduncles using diffusion tensor imaging is useful in cases when a cerebellar peduncle lesion is suspected.     

Local tissue anisotropy decreases in cerebellopetal fibers and pyramidal tract in multiple system atrophy

Background One of the cardinal features in multiple system atrophy (MSA) is the white matter pathology: loss of myelin, astrocytosis, and glial cytoplasmic inclusions. The pathological changes of tissue microstructure can modify the diffusion behavior of water molecules, which can be assessed by diffusion tensor imaging (DTI). Objectives To explore the hypothesis of white matter degeneration in MSA. Methods We studied 11 patients with clinically probable MSA and 10 age–matched controls. DTI was performed in both groups to measure fractional anisotropy (FA) in various regions of interest: the inferior cerebellar peduncle (ICP), middle cerebellar peduncle (MCP), superior cerebellar peduncle (SCP), basis pontis, internal capsule, and corpus callosum. Results FA values in SCP and corpus callosum showed no significant difference between the MSA group and controls. By contrast, FA values decreased in the MSA group in the MCP, basis pontis and internal capsule. In addition, FA values in the MCP were negatively correlated with ataxia severity in the MSA group. Conclusion The areas showing decreased tissue anisotropy in DTI corresponded well with pathologically vulnerable areas in MSA. In addition, the local tissue anisotropy of MCP decreased in accordance with functional disability. These observations implied that DTI is a feasible method for in vivo evaluation of the white matter pathology in MSA.This work was supported by funds from the Japanese Ministry of Education, Science and Technology (Grant number 14770295).     

Altered Microstructural Connectivity of the Superior Cerebellar Peduncle is Related to Motor Dysfunction in Children with Autistic Spectrum Disorders

Many studies have reported motor impairments in autistic spectrum disorders (ASD). However, the brain mechanism underlying motor impairment in ASD remains unclear. Recent neuroimaging studies have suggested that underconnectivity between the cerebellum and other brain regions contributes to the features of ASD. In this study, we investigated the microstructural integrity of the cerebellar pathways, including the superior, middle, and inferior cerebellar peduncles, of children with and without ASD by using diffusion tensor imaging (DTI) tractography to determine whether the microstructural integrity of the cerebellar pathways is related to motor function in children with ASD. Thirteen children with ASD and 11 age-, gender-, handedness-, and IQ-matched typically developing (TD) controls were enrolled in this study. DTI outcome measurements, such as fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD), for the cerebellar pathways were calculated. The Movement Assessment Battery for Children 2 (M-ABC 2) was used for assessing motor functions. There were no significant differences between the two groups in RD. However, compared to the TD subjects, patients with ASD had a significantly lower FA in the right superior cerebellar peduncle and lower AD in the left superior cerebellar peduncle, in addition to a significantly lower score in ball skills and the total test score of M-ABC 2. There was a significant positive correlation between the total test score of M-ABC 2 and FA in the right superior cerebellar peduncle in the ASD group. These findings suggest that the altered microstructural integrity of the superior cerebellar peduncle may be related to motor impairment in ASD.     

Diffusion tensor imaging for measuring recovery from cerebellar peduncle injury due to intracerebral hemorrhage A case report

Diffusion tensor tractography (DTT) in diffusion tensor imaging (DTI) examination allows for the three-dimensional visualization of cerebellar peduncles. The present case-control study analyzed the relationship between functional recovery of intracerebral hematoma patient and cerebellar peduncle injury, as detected by DTI. The enrolled patient could not sit at 3 weeks after onset, but was able to walk independently and perform most daily activities after 4 months. The 3-week DTT images revealed that all six cerebellar peduncles were compressed by the hematoma, posterior portions of all three left cerebellar peduncles were shortened, and the left middle cerebellar peduncle was interrupted in the mid-portion. The 4-week DTT images showed that all compressed cerebellar peduncles were ameliorated, although injured posterior portions of the three left cerebellar peduncles did not recover. The fractional anisotropy value of the right inferior cerebellar peduncle increased from two standard deviations below the normal control value to within two standard deviations of the normal control value. These findings suggested that functional recovery was primarily due to decompression of compressed cerebellar peduncles, and not to recovery of injured cerebellar peduncles. DTI evaluations of cerebellar peduncles could be helpful when cerebellar peduncle injury is suspected.     

Diffusion tensor imaging (DTI) and tractography of the cerebellar projections to prefrontal and posterior parietal cortices: a study at 3T

OBJECTIVES: Previous diffusion tensor imaging (DTI) studies have identified cerebellar pathways and supratentorial connections, but none of them have isolated cerebellar projections to prefrontal and posterior parietal cortices using tractography. The aim of our study was to identify and visualize on 3D projections, as well as on 2D cross-sectional images, the cerebellar projections to prefrontal (PF) and posterior parietal (PP) cortices. MATERIAL AND METHODS: The study included 10 healthy volunteers, four males and six females aged 25 to 45 years (mean age 31 years). A DTI sequence was applied at 3 Tesla using diffusion sensitizing gradients in 32 directions. White matter tracts were reconstructed by applying a multiple ROI (region of interest) tractography technique. RESULTS: PF projections were obtained in all subjects. PP projections were obtained in six over 10 subjects. On 2D cross-sectional images, the tracts showed the same anatomical location in each ROI in all subjects. CONCLUSION: This DTI study at 3T resulted in a selective and full visualization of cerebellar projections to PF and PP cortices for the first time and is introductive for further optimized and quantitative DTI study of these tracts.     

Plasticity of the Superior and Middle Cerebellar Peduncles in Musicians Revealed by Quantitative Analysis of Volume and Number of Streamlines Based on Diffusion Tensor Tractography

This work was conducted to study the plasticity of superior (SCP) and middle (MCP) cerebellar peduncles in musicians. The cerebellum is well known to support several musically relevant motor, sensory and cognitive functions. Previous studies reported increased cerebellar volume and grey matter (GM) density in musicians. Here, we report on plasticity of white matter (WM) of the cerebellum. Our cohort included 10/10 gender and handedness-matched musicians and controls. Using diffusion tensor imaging, fibre tractography of SCP and MCP was performed. The fractional anisotropy (FA), number of streamlines and volume of streamlines of SCP/MCP were compared between groups. Automatic measurements of GM and WM volumes of the right/left cerebellar hemispheres were also compared. Musicians have significantly increased right SCP volume (p = 0.02) and number of streamlines (p = 0.001), right MCP volume (p = 0.004) and total WM volume of the right cerebellum (p = 0.003). There were no significant differences in right MCP number of streamlines, left SCP/MCP volume and number of streamlines, SCP/MCP FA values, GM volume of the right cerebellum and GM/WM volumes of the left cerebellum. We propose that increased volume and number of streamlines of the right cerebellar peduncles represent use-dependent structural adaptation to increased sensorimotor and cognitive functional demands on the musician's cerebellum.     

功能磁共振和弥散张量纤维束成像中的人脑皮质桥小脑束

The anatomical organization of the corticopontocerebellar tract(CPCT) in the human brain remains poorly understood.The present study investigated probabilistic tractography of the CPCT in the human brain using diffusion tensor tractography with functional magnetic resonance imaging.CPCT data was obtained from 14 healthy subjects.CPCT images were obtained from functional magnetic resonance imaging and diffusion tensor tractography,revealing that the CPCT originated from the primary sensorimotor cortex and descended to the pontine nucleus through the corona radiata,the posterior limb of the internal capsule,and the cerebral peduncle.After crossing the pons through the transverse pontine fibers,the CPCT entered the cerebellum via the middle cerebral peduncle.However,some variation was detected in the midbrain(middle cerebral peduncle and/or medial lemniscus) and pons(ventral and/or dorsal transverse pontine fibers).The CPCT was analyzed in 3 dimensions from the cerebral cortex to the cerebellum.These results could be informative for future studies of motor control in the human brain.     

Tecto-cerebellar dysraphism with occipital encephalocele: not a distinct disorder, but part of the Joubert syndrome spectrum?

Magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) findings in a 4-year-old child with occipital encephalocele, cerebellar vermis hypogenesis, and tectal malformation are presented. The neuroimaging findings are reminiscent of tectocerebellar dysraphism with an occipital encephalocele (TCD-OE). Additionally, elongated, thickened, and horizontally orientated superior cerebellar peduncles, an abnormally deepened interpeduncular fossa, subependymal heterotopia, and focal cortical dysplasia were noted. Color-coded fractional anisotropy (FA) maps revealed an absence of the decussation of the superior cerebellar peduncles. These findings are highly suggestive of Joubert syndrome and related disorders (JSRD). Our report and the review of the published cases suggest that TCD-OE is not a nosological entity, but may represent the structural manifestation of heterogeneous disorders such as the JSRD spectrum. DTI may be very helpful to differentiate between similar midbrain-hindbrain malformations.     

Cerebellar Pathways in Mouse Model of Purkinje Cell Degeneration Detected by High-Angular Resolution Diffusion Imaging Tractography

Cerebellar MR imaging has several challenging aspects, due to the fine, repetitive layered structure of cortical folia with underlying axonal pathways. In this MR study, we imaged with high-angular resolution diffusion imaging (HARDI) abnormal cerebellar cortical structure (gray matter) and myelinated axonal pathways (white matter) of a mouse spontaneous mutation, Purkinje cell degeneration (pcd), in which almost all Purkinje neurons degenerate, mainly between postnatal days 20 and 35. Mouse brains at postnatal day 20 (P20) and at 8 months were scanned, and known or expected abnormalities, such as reduction of the white matter volume, disorganized pathways likely linked to parallel fibers, mossy fibers, and other fibers running from/to the cerebellar cortex were observed in mutant mice. Such abnormalities were detected at both an early and a fully advanced degeneration stage. These results suggest that our diffusion MR tractography is useful for early detection and tracking of neuropathology in the cerebellum.     

Radial diffusivity in the cerebellar peduncles correlates with clinical severity in Friedreich ataxia

Friedreich ataxia (FRDA) is a common inherited ataxia, caused by an expanded GAA repeat sequence in the Frataxin (FXN) gene. The proprioceptive system, which enters the cerebellum through the cerebellar peduncles, is a primary focus of pathology. In this study, we investigate the relationship of clinical and genetic data with diffusion-tensor imaging (DTI) indices reflecting white matter integrity of the cerebellar peduncles. Nine FRDA patients underwent DTI. After between-subject registration using tract-based spatial statistics, a white matter atlas was used for computing average values of DTI indices in the regions of interest. These were the inferior, middle and superior cerebellar peduncles (ICP, MCP, SCP). For Bonferroni correction, significance threshold was set to p < 0.0056. We found that radial diffusivity (D^⊥) within the ICP significantly correlated with scores on the Friedreich Ataxia Rating Scale (FARS, Spearman’s ρ = 0.883, p = 0.0016, all two-sided) and, at trend level, with number of trinucleotide repeats (ρ = 0.812, p = 0.008). D^⊥ in the SCP correlated with scores on the Scale for the Assessment and Rating of Ataxia (SARA, ρ = 0.867, p = 0.0025). These findings support the role of DTI, and especially D^⊥, as an informative biomarker in FRDA.     

Magnetoencephalography and diffusion tensor imaging in gelastic seizures secondary to a cingulate gyrus lesion

Gelastic seizures are relatively uncommon and rarely observed secondary to frontal lobe lesions. This report presents magnetoencephalography (MEG) and diffusion tensor imaging (DTI) findings in an adolescent with gelastic seizures secondary to a left anterior cingulate gyrus lesion. Ictal scalp video EEG showed bilateral frontal 4 Hz theta discharges. Interictal EEG showed left fronto-temporal spikes or sharp waves. Interictal MEG showed spike sources over bilateral temporal regions. DTI and tractography delineated slightly shifted corpus callosum posterior to the lesion, unaffected uncinate and inferior longitudinal fasciculi. The patient became seizure free for 12 months after surgical excision of a pleomorphic xanthoastrocytoma in the left anterior cingulate region. In our patient, MEG and EEG did not localize the deep-seated epileptogenic zone. The combination of DTI and neurophysiologic studies, however, possibly disclosed neuronal connections within the epileptic network and indicated that epileptic discharges propagated via the uncinate fibers from the primary epileptogenic zone in the anterior cingulate region to the mesial temporal region in this case with gelastic seizures secondary to a cingulate lesion.     

White matter integrity of the cerebellar peduncles as a mediator of effects of prenatal alcohol exposure on eyeblink conditioning

Fetal alcohol spectrum disorders (FASD) are characterized by a range of neurodevelopmental deficits that result from prenatal exposure to alcohol. These can include cognitive, behavioural, and neurological impairment, as well as structural and functional brain damage. Eyeblink conditioning (EBC) is among the most sensitive endpoints affected in FASD. The cerebellar peduncles, large bundles of myelinated nerve fibers that connect the cerebellum to the brainstem, constitute the principal white matter element of the EBC circuit. Diffusion tensor imaging (DTI) is used to assess white matter integrity in fibre pathways linking brain regions. DTI scans of 54 children with FASD and 23 healthy controls, mean age 10.1 ± 1.0 years, from the Cape Town Longitudinal Cohort were processed using voxelwise group comparisons. Prenatal alcohol exposure was related to lower fractional anisotropy (FA) bilaterally in the superior cerebellar peduncles and higher mean diffusivity (MD) in the left middle peduncle, effects that remained significant after controlling for potential confounding variables. Lower FA and higher MD in these regions were associated with poorer EBC performance. Moreover, effects of alcohol exposure on EBC decreased significantly after inclusion of these DTI measures in regression models, suggesting that these white matter deficits partially mediate the relation of prenatal alcohol exposure to EBC. The associations of greater alcohol consumption with these DTI measures are largely attributable to greater radial diffusivity, possibly indicating poorer myelination. Thus, these data suggest that fetal alcohol‐related deficits in EBC are attributable, in part, to poorer myelination in key regions of the cerebellar peduncles. Hum Brain Mapp 36:2470–2482, 2015. © 2015 Wiley Periodicals, Inc.