Predicting patterns of glioma recurrence using diffusion tensor imaging

Although multimodality therapy for high-grade gliomas is making some improvement in outcome, most patients will still die from their disease within a short time. We need tools that allow treatments to be tailored to an individual. In this study we used diffusion tensor imaging (DTI), a technique sensitive to subtle disruption of white-matter tracts due to tumour infiltration, to see if it can be used to predict patterns of glioma recurrence. In this study we imaged 26 patients with gliomas using DTI. Patients were imaged after 2 years or on symptomatic tumour recurrence. The diffusion tensor was split into its isotropic (p) and anisotropic (q) components, and these were plotted on T₂-weighted images to show the pattern of DTI abnormality. This was compared to the pattern of recurrence. Three DTI patterns could be identified: (a) a diffuse pattern of abnormality where p exceeded q in all directions and was associated with diffuse increase in tumour size; (b) a localised pattern of abnormality where the tumour recurred in one particular direction; and (c) a pattern of minimal abnormality seen in some patients with or without evidence of recurrence. Diffusion tensor imaging is able to predict patterns of tumour recurrence and may allow better individualisation of tumour management and stratification for randomised controlled trials.     

Combining Diffusion Tensor Metrics and DSC Perfusion Imaging: Can It Improve the Diagnostic Accuracy in Differentiating Tumefactive Demyelination from High-Grade Glioma?

BACKGROUND AND PURPOSE:Tumefactive demyelinating lesions with atypical features can mimic high-grade gliomas on conventional imaging sequences. The aim of this study was to assess the role of conventional imaging, DTI metrics (p:q tensor decomposition), and DSC perfusion in differentiating tumefactive demyelinating lesions and high-grade gliomas.MATERIALS AND METHODS:Fourteen patients with tumefactive demyelinating lesions and 21 patients with high-grade gliomas underwent brain MR imaging with conventional, DTI, and DSC perfusion imaging. Imaging sequences were assessed for differentiation of the lesions. DTI metrics in the enhancing areas and perilesional hyperintensity were obtained by ROI analysis, and the relative CBV values in enhancing areas were calculated on DSC perfusion imaging.RESULTS:Conventional imaging sequences had a sensitivity of 80.9% and specificity of 57.1% in differentiating high-grade gliomas (P = .049) from tumefactive demyelinating lesions. DTI metrics (p:q tensor decomposition) and DSC perfusion demonstrated a statistically significant difference in the mean values of ADC, the isotropic component of the diffusion tensor, the anisotropic component of the diffusion tensor, the total magnitude of the diffusion tensor, and rCBV among enhancing portions in tumefactive demyelinating lesions and high-grade gliomas (P ≤ .02), with the highest specificity for ADC, the anisotropic component of the diffusion tensor, and relative CBV (92.9%). Mean fractional anisotropy values showed no significant statistical difference between tumefactive demyelinating lesions and high-grade gliomas. The combination of DTI and DSC parameters improved the diagnostic accuracy (area under the curve = 0.901). Addition of a heterogeneous enhancement pattern to DTI and DSC parameters improved it further (area under the curve = 0.966). The sensitivity increased from 71.4% to 85.7% after the addition of the enhancement pattern.CONCLUSIONS:DTI and DSC perfusion add profoundly to conventional imaging in differentiating tumefactive demyelinating lesions and high-grade gliomas. The combination of DTI metrics and DSC perfusion markedly improved diagnostic accuracy.

Tumefactive demyelinating lesions (TDLs) are demyelinating lesions of >2 cm and can mimic high-grade gliomas (HGGs) on conventional MR imaging.¹ Classic conventional and advanced imaging findings may not be present in all cases.^2–4 Because TDLs can be mistaken for gliomas on histopathology, demonstration of the intact axonal process and myelin breakdown products within macrophages is confirmative of demyelination.^5–7 This diagnostic dilemma might lead to a biopsy, an inadvertent operation, and even radiation therapy, which eventually can exacerbate demyelination.Diffusion tensor imaging is a noninvasive method for analyzing the architectural integrity and orientation of axons in white matter. The eigenvalues can be used to calculate various scalar measures of DTI metrics such as ADC, fractional anisotropy (FA), the isotropic component of the diffusion tensor (p), the anisotropic component of the diffusion tensor (q), and the total magnitude of the diffusion tensor (L).^8–10 The most commonly used DTI parameters include ADC (ie, the magnitude of diffusion independent of tissue orientation) and FA (ie, anisotropic diffusion against the total magnitude of diffusion). Less often used measures include total magnitude of diffusion tensor (L) and its isotropic (p) and anisotropic (q) components.The use of FA as a sole measure of anisotropic diffusion can be fallacious because it varies with changes in the anisotropic component and the total magnitude of diffusion.^9,10 The utility of DTI parameters (ie, FA, p, q, and L) has been evaluated in the differentiation of various brain tumors.^11–13 Toh et al¹⁴ evaluated the role of FA in differentiating TDL from HGG by using DTI. However, to the best of our knowledge, there are no studies available evaluating the role of p, qd , and L in differentiating TDL and HGG.Dynamic-susceptibility contrast perfusion imaging allows evaluation of relative cerebral blood volume (rCBV), a marker of neoangiogenesis, and aids in the differentiation of low- and high-grade gliomas.^15,16 TDLs usually have decreased rCBV values due to the absence of neovascular proliferation, which allows differentiation of TDL from HGG.¹⁷ However, TDL can also present with elevated rCBV values and mimic HGG on DSC perfusion, making differentiation difficult.⁴The purpose of this study was to evaluate the efficacy of conventional imaging, diffusion tensor metrics (ADC, FA, p, q, and L), and DSC perfusion (rCBV) in differentiating TDL and HGG. We also assessed the effect of combining imaging parameters—DTI and DSC perfusion imaging—on diagnostic accuracy.     

扩散张量成像对胶质瘤分级的应用价值

胶质瘤是脑内最常见的恶性肿瘤,胶质瘤分级对其治疗方案的选择及预后判断尤为重要。扩散张量成像(DTI)是目前唯一可以在活体状态下无创性检测组织微观结构的功能成像方法。DTI对水分子运动敏感,尤其是沿着轴突纤维束分布的水分子,而胶质瘤肿瘤细胞浸润主要沿着白质神经束走行,低级别胶质瘤的神经轴扩散率为3.7%~5.3%,而高级别胶质瘤为10%~27%,因此DTI对胶质瘤的分级诊断具有重要的价值。现就近年来DTI对胶质瘤分级诊断的研究现状及研究前景等方面内容进行综述。     

Impact of white matter hyperintensities on surrounding white matter tracts

Purpose

It is unclear how white matter hyperintensities disrupt surrounding white matter tracts. The aim of this tractography study was to determine the spatial relationship between diffusion characteristics along white matter tracts and the distance from white matter hyperintensities.

Methods

Diffusion tensor 3-T MRI scans were acquired in 29 participants with white matter hyperintensities. In each subject, tractography by the fiber assignment by continuous tracking method was used to segment corticospinal tracts. Mean diffusivity, radial diffusivity, axial diffusivity, and fractional anisotropy were measured along corticospinal tracts in relation to white matter hyperintensities. Diffusion characteristics along tracts were correlated with distance from white matter hyperintensities and were also compared between tracts traversing and not traversing white matter hyperintensities.

Results

In tracts not traversing through white matter hyperintensities, increasing distance from white matter hyperintensities was associated with decreased mean diffusivity (p?=?0.002) and increased fractional anisotropy (p?=?0.006). In tracts traversing white matter hyperintensities, compared to tracts not traversing white matter hyperintensites, the mean diffusivity was higher at 6–8 voxels, axial diffusivity higher at 4–8 voxels, and radial diffusivity higher at 7 voxels away from white matter hyperintensities (all p?<?0.006).

Conclusion

White matter hyperintensities are associated with two patterns of altered diffusion characteristics in the surrounding white matter tract network. Diffusion characteristics along white matter tracts improve further away from white matter hyperintensities suggestive of a local penumbra pattern. Also, altered diffusion extends further along tracts traversing white matter hyperintensities suggestive of a Wallerian-type degenerative pattern.

     

Magnetic resonance diffusion tensor imaging for characterizing diffuse and focal white matter abnormalities in multiple sclerosis.

High-resolution diffusion tensor imaging (DTI) was performed in 14 patients with clinically definite multiple sclerosis (MS) and the trace of the diffusion tensor () and the fractional anisotropy (FA) were determined in normal appearing white matter (NAWM) and in different types of focal MS lesions. A small but significant increase of the in NAWM compared to control white matter ((840 +/- 85) x 10(-6) mm(2)/sec vs. (812 +/- 59) x 10(-6) mm(2)/sec; P < 0.01) was found. In addition, there was a significant decrease in the FA of normal-appearing regions containing well-defined white matter tracts, such as the genu of the internal capsule. In non-acute lesions, the of T(1)-hypointense areas was significantly higher than that of T(1)-isointense lesions ((1198 +/- 248) x 10(-6) mm(2)/sec vs. (1006 +/- 142) x 10(-6) mm(2)/sec; P < 0. 001), and there was a corresponding inverse relation of FA. Diffusion characteristics of active lesions with different enhancement patterns were also significantly different. DTI with a phase navigated interleaved echo planar imaging technique may be used to detect abnormalities of isotropic and anisotropic diffusion in the NAWM and selected fiber tracts of patients with MS throughout the entire brain, and it demonstrates substantial differences between various types of focal lesions.     

Preliminary experience with visualization of intracortical fibers by focused high-resolution diffusion tensor imaging

BACKGROUND AND PURPOSE: The inherent low anisotropy of gray matter and the lack of adequate imaging sensitivity and resolution has, so far, impeded depiction of axonal fibers to their intracortical origin or termination. We tested the hypothesis that an experimental approach with high-resolution diffusion tensor imaging (DTI) provides anisotropic data for fiber tractography with sufficient sensitivity to visualize in vivo the fine distribution of white matter bundles at the intracortical level.MATERIALS AND METHODS: We conducted phantom measurements of signal-to-noise ratio (SNR) and obtained diffusion tensor maps of the occipital lobe in 6 healthy volunteers using a dedicated miniature phased array detector at 3T. We reconstructed virtual fibers using a standard tracking algorithm.RESULTS: The coil array provided a SNR of 8.0 times higher at the head surface compared with a standard quadrature whole head coil. Diffusion tensor maps could be obtained with an in-plane resolution of 0.58 × 0.58 mm². The axonal trajectories reconstructed from the diffusion data penetrate into the cortical ribbon perpendicular to the pial surface. This is the expected pattern for the terminations of thalamocortical afferent fibers to the middle layers of the occipital cortex and is consistent with the known microstructural organization of the mammalian cerebral cortex.CONCLUSION: High-resolution DTI reveals intracortical anisotropy with a distinct parallel geometrical order, perpendicular to the pial surface, consistent with structures that may be identified as the terminal afferents in cortical gray matter.

A noninvasive method that seems promising for the investigation of the neuronal network in the living human brain is diffusion tensor imaging (DTI).^1,2 Parameters associated with the diffusion tensor, such as fractional anisotropy (FA),^2,3 give an indication of the degree of tissue organization. In the measurement of the molecular diffusion of water along neural pathways, DTI techniques have been widely applied for determining the orientation of fiber bundles in the white matter of the human brain.^4,5To study connectivity in the human brain, fiber tracts should be reconstructed and followed to their intracortical neuronal origin or terminations in the gray matter. In white matter, axonal membranes and myelination modulate the degree of anisotropic water diffusion,⁶ whereas gray matter has relatively low anisotropy and thus is extremely difficult to reconstruct by DTI. Directional diffusion properties in the gray matter are complicated by a significant component of parallel interconnecting fibers, both within and between cortical layers. Conversely, no anatomic structure extends through the full cortical thickness, and the cell bodies of cortical neurons produce quasi-isotropic water diffusion. Thus, the resulting diffusion tensor in the gray matter appears either more isotropic without fully reflecting the microscopic anisotropy, or it contains a set of diffusion directions similar to that of a single specific preferred direction. Resolving intravoxel heterogeneity can be achieved either by increasing the spatial resolution, or by developing alternative strategies (eg, modeling of the diffusion process in the neural tissue) that are able to resolve multiple intravoxel fiber directions.^7,8A few studies so far have described distinct anisotropy at the cortical gray matter in experimental animals,^9,10 in the fetal cerebrum,¹¹ and more recently in the adult brain, though at a low spatial resolution.¹² All of these studies emphasized that image resolution is of utmost importance for the extraction of anisotropic data for fiber tractography.In our study, we tested the hypothesis that a high-resolution DTI experimental approach can provide anisotropic data with a distinct geometric order that would allow in vivo visualization of the fine distribution of axonal bundles at the intracortical level. By using an imaging approach, we combined miniature surface coils with the application of parallel imaging on a 3T MR system. We expected that this combination would provide sufficient sensitivity and resolution to detect in vivo the anisotropic organization of thalamocortical afferents and their reconstruction at the corticomedullary junction and, eventually, intracortically.     

Diffusion tensor imaging for target volume definition in glioblastoma multiforme

Introduction

Diffusion tensor imaging (DTI) is an MR-based technique that may better detect the peritumoural region than MRI. Our aim was to explore the feasibility of using DTI for target volume delineation in glioblastoma patients.

Materials and methods

MR tensor tracts and maps of the isotropic (p) and anisotropic (q) components of water diffusion were coregistered with CT in 13 glioblastoma patients. An in-house image processing program was used to analyse water diffusion in each voxel of interest in the region of the tumour. Tumour infiltration was mapped according to validated criteria and contralateral normal brain was used as an internal control. A clinical target volume (CTV) was generated based on the T₁-weighted image obtained using contrast agent (T_1Gd), tractography and the infiltration map. This was compared to a conventional T₂-weighted CTV (T₂-w CTV).

Results

Definition of a diffusion-based CTV that included the adjacent white matter tracts proved highly feasible. A statistically significant difference was detected between the DTI-CTV and T₂-w CTV volumes (p?t?=?3.480). As the DTI-CTVs were smaller than the T₂-w CTVs (tumour plus peritumoural oedema), the pq maps were not simply detecting oedema. Compared to the clinical planning target volume (PTV), the DTI-PTV showed a trend towards volume reduction. These diffusion-based volumes were smaller than conventional volumes, yet still included sites of tumour recurrence.

Conclusion

Extending the CTV along the abnormal tensor tracts in order to preserve coverage of the likely routes of dissemination, whilst sparing uninvolved brain, is a rational approach to individualising radiotherapy planning for glioblastoma patients.     

Improved delineation of glioma margins and regions of infiltration with the use of diffusion tensor imaging: an image-guided biopsy study

BACKGROUND AND PURPOSE: The efficacy of radiation therapy, the mainstay of treatment for malignant gliomas, is limited by our inability to accurately determine tumor margins. As a result, despite recent advances, the prognosis remains appalling. Because gliomas preferentially infiltrate along white matter tracks, methods that show white matter disruption should improve this delineation. In this study, results of histologic examination from samples obtained from image-guided brain biopsies were correlated with diffusion tensor images. METHODS: Twenty patients requiring image-guided biopsies for presumed gliomas were imaged preoperatively. Patients underwent image-guided biopsies with multiple biopsies taken along a single track that went into normal-appearing brain. Regions of interest were determined from the sites of the biopsies, and diffusion tensor imaging findings were compared with glioma histology. RESULTS: Using diffusion tissue signatures, it was possible to differentiate gross tumor (reduction of the anisotropic component, q > 12% from contralateral region), from tumor infiltration (increase in the isotropic component, p > 10% from contralateral region). This technique has a sensitivity of 98% and specificity of 81%. T2-weighted abnormalities failed to identify the margin in half of all specimens. CONCLUSION: Diffusion tensor imaging can better delineate the tumor margin in gliomas. Such techniques can improve the delineation of the radiation therapy target volume for gliomas and potentially can direct local therapies for tumor infiltration.     

Clinical applications of diffusion tensor tractography of the spinal cord

Diffusion tensor imaging (DTI) can visualize the white matter tracts in vivo. The aim of this study was to assess the clinical utility of DTI in patients with diseases of the spinal cord. Fourteen subjects underwent magnetic resonance imaging of the spine at 1.5 T. Preliminary diagnosis of the patients suggested traumatic, tumorous, ischemic or inflammatory lesions of the spinal cord. In addition to T2-weighted images, DTI was performed with the gradients in 30 orthogonal directions. Maps of the apparent diffusion coefficient and of fractional anisotropy were reconstructed. Diffusion tensor imaging showed a clear displacement and deformation of the white matter tracts at the level of the pathological lesions in the spinal cord. This capability of diffusion tensor imaging to reliably display secondary alterations to the white matter tracts caused by the primary lesion has the potential to be of great utility for treatment planning and follow-up.     

Voxel-based diffusion tensor imaging detects pyramidal tract degeneration in primary lateral sclerosis

Objective

Primary lateral sclerosis (PLS) is a progressive degenerative disorder affecting upper motor neurons and requires a clinical diagnosis. Diffusion tensor imaging (DTI) is a quantitative method for assessing white matter fibre integrity. The purpose of the study was to evaluate the involvement of upper motor neurons by using DTI in PLS.

Methods

A patient with PLS was compared with eight age-matched controls. Differences in fractional anisotropy (FA) index were assessed using DTI on a voxel-by-voxel basis.

Results

Decreased FA was observed in the proximal part of the pyramidal tract bilaterally, which indicated degeneration of the pyramidal cells.

Conclusion

Voxel-based DTI could be used as an objective marker for detecting upper motor neuron degeneration in PLS.Primary lateral sclerosis (PLS) is an adult onset, non-hereditary degenerative disorder of the upper motor neuron related to a selective loss of precentral pyramidal neurons. Ιt is characterised by progressive spinobulbar spasticity owing to pyramidal tract degeneration, but preservation of the anterior horn motor neurons and no involvement of the lower motor neuron [1–4]. Currently there is no defining test or disease marker; thus, the diagnosis is usually made based on clinical presentation [1, 2].Diffusion tensor imaging (DTI) is an MRI technique that provides information about white matter fibre orientation and integrity in vivo based on the principles of free water molecules movement. Water molecules move in a random manner (isotropic diffusion); however, the presence of obstacles, such as axonal membranes and myelin sheaths, restrict the motion in a particular direction resulting in anisotropic diffusion. The fractional anisotropy (FA) index is a measure of the degree of directionality of diffusion [5, 6]. The assessment of FA has been used as a measure of white matter degeneration in many diseases as it can detect and quantify the degeneration of fibres along white matter tracts [5, 6]. The method that is usually used is the region of interest (ROI) approach [7]. Nowadays, an automated method of analysis is used for a voxel-wise comparison of DTI data throughout the whole brain [8, 9].In this report a single case of PLS was studied using DTI on a voxel-by-voxel comparison with a control group to detect upper motor neuron involvement.     

正常成人脑结构的弥散张量成像参数测定及分析

目的　运用弥散张量成像 (DTI)方法来探讨脑内不同组织及解剖部位的弥散各向异性特点。资料与方法　采用单次激发自旋回波EPI成像序列 ,将弥散敏感梯度依次施加在六个不同 (P、M、S、MP、PS、MS)的方向进行DTI,获得正常成人脑的弥散张量图及各向异性指数图 ,在脑内不同解剖部位进行各向异性指数、张量的轨迹及平均弥散率测定并进行统计学分析。结果　脑内不同组织及解剖部位的弥散各向异性程度不同 ,脑白质的弥散各向异性远大于丘脑与脑灰质 (P <0 .0 1) ;在脑白质的不同解剖部位 ,其各向异性特点也不相同 (P <0 .0 5 ) ,脑白质连合纤维 (胼胝体 )的各向异性程度最高 ,其次为脑白质的投射纤维 (内囊 ) ,再次为联合纤维 (半卵圆中心 )。张量的轨迹及平均弥散率在脑内的不同部位具有一致性。结论　DTI可准确测定脑内不同组织弥散的各向异性特点 ,并且可清晰显示脑内神经纤维束的方向及走行 ,可为临床脑白质病的研究提供新的功能测定方法     

Diffusion tensor imaging in chronic subdural hematoma: correlation between clinical signs and fractional anisotropy in the pyramidal tract

BACKGROUND AND PURPOSE: Diffusion tensor imaging (DTI) was introduced as a good technique to evaluate structural abnormalities in the white matter. In this study, we used DTI to examine anisotropic changes of the pyramidal tracts displaced by chronic subdural hematoma (CSDH).MATERIALS AND METHODS: Twenty-six patients with unilateral CSDH underwent DTI before and after surgery. We measured fractional anisotropy (FA) values in pyramidal tracts of bilateral cerebral peduncles and calculated the ratio of the FA value on the lesion side to that on the contralateral side (FA ratio) and compared the ratios with motor weakness. Moreover, the relationships between FA ratios and clinical factors such as age, sex, midline shift, interval from trauma, and hematoma attenuation on CT were evaluated.RESULTS: FA values of pyramidal tracts on the lesion side were significantly lower than those on the contralateral side (0.66 ± 0.07 versus 0.74 ± 0.05, P < .0001). The FA ratio was correlated to the severity of motor weakness (r² = 0.32, P = .002). FA ratios after surgery improved significantly compared with those before surgery (0.96 ± 0.08 versus 0.89 ± 0.07, P = .0004). Intervals from trauma and the midline shift were significantly associated with decreased FA ratios (P = .0008 and P = .037).CONCLUSIONS: In patients with CSDH, a reversible decrease of FA in the affected pyramidal tract on DTI was correlated to motor weakness. These anisotropic changes were considered to be caused by a reversible distortion of neuron fibers and vasogenic edema due to the hematoma.

Chronic subdural hematoma (CSDH) is a progressive space-occupying lesion, which may lead to reversible reduction in cerebral function due to brain compression or brain displacement. The causes, clinical characteristics, and therapeutic management of CSDH are well established; however, the detailed physiology, including the mechanisms of appearance with motor dysfunction in patients, is still controversial.^1–4Diffusion tensor imaging (DTI) reveals the tissue microstructure and architecture of white matter tracts, including pyramidal tracts, and extracts the principal diffusivities, mean diffusivities (MD), and fractional anisotropy (FA). Previously, it was reported that decreased FA in the pyramidal tracts on DTI was associated with secondary degeneration and could be a reliable measure of motor weakness.^5–8 The purpose of this study was to investigate changes of DTI in affected pyramidal tracts of patients with CSDH and to evaluate the association between changes of FA and clinical factors such as age, sex, hematoma thickness, midline shift, interval from the trauma, and attenuation on CT.     

Theory of diffusion tensor imaging and fiber tractography analysis

Magnetic Resonance Imaging (MRI) techniques have been increasingly applied to the study of molecular displacement (diffusion) in biologic tissue. The magnetic resonance measurement of an effective diffusion tensor of water in tissues can provide unique biologically and clinically relevant information that is not available from other imaging modalities. For this purpose Diffusion Tensor Imaging (DTI) is applied. DTI is an MRI variation that may significantly improve our understanding of brain structure and neural connectivity. DTI measures are thought to be representative of brain tissue microstructure and are particularly useful for examining organized brain regions, such as white matter tract areas. DTI measures the water diffusion tensor using diffusion weighted pulse sequences sensitive to microscopic random water motion. The resultant images display and allow for quantification of how water diffuses along axes or diffusion encoding directions. This can help measure and quantify a tissue's orientation and structure, making it an ideal tool for examining cerebral white matter and neural fiber tracts. In this article we discuss the theory on which DTI depends on, how can be used in mapping fiber tracts. Also the fiber tracking algorithms are presented.     

Regional differences in diffusion tensor imaging measurements: assessment of intrarater and interrater variability

BACKGROUND AND PURPOSE: Diffusion tensor imaging (DTI) has become a valuable tool in both the research and clinical evaluation of subjects. We sought to quantify interobserver and intraobserver variability of diffusivity and diffusion anisotropy measurements with regard to specific regions of interest (ROIs).MATERIALS AND METHODS: The subject group consisted of 5 healthy control subjects and 7 study subjects (all males; 16–19 years old; mean age = 17.5 years), as part of a protocol for closed head injury. Two whole-brain DTI scans were acquired on a 3T scanner for each subject. Analysis was performed using a ROI approach. Two independent observers analyzed the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) indices in the corpus callosum, cortical spinal tract, internal capsules (ICs), basal ganglia, and centrum semiovale (CSO). Intraobserver and interobserver variability were calculated for the mean ADC, FA, and ordered eigenvalues of the diffusion tensor (λ₁, λ₂, and λ₃).RESULTS: The overall κ statistic for intraobserver variability for both observers showed slight-to-substantial agreement (κ = 0.02–0.69), however FA values in the CSO showed only slight agreement. Interobserver agreement was also slight to substantial for these DTI measurements with high variability in FA values in the IC and CSO.CONCLUSIONS: When one is comparing 2 DTI measurements, it is important to assess intraobserver and interobserver variability. We recommend caution in the analysis of DTI contrasts in the IC and CSO, because we have found the widest range of variability in measurements within these structures.

Diffusion tensor imaging (DTI) has become well established as a research tool to investigate water diffusion properties in the central nervous system and is making inroads into clinical imaging. It is a safe, noninvasive in vivo method that allows a superior assessment (compared with conventional MR imaging) of white matter tracts by reconstructing their 3D shape and connectivity. Parameters derived from DTI can provide information about tissue organization, degree of myelination, and water mobility, enabling the study of white matter tract direction, integrity, and damage in the brain.¹ Although DTI was initially used for anatomic purposes to understand human brain anatomy and to topographically depict the white matter tracts of the brain, the technique has increasingly been used to study changes in pathology by comparing quantifiable metrics of diffusion.Two important parameters derived from DTI are the apparent diffusion coefficient (ADC) and fractional anisotropy (FA).¹ The ADC and FA parameters characterize the average amount of diffusion and the diffusion anisotropy, respectively.² These parameters are derived from the eigenvalues (λ₁, λ₂, and λ₃) computed from the diffusion tensor. The diffusivity measurements from the eigenvalues themselves can also be used to study tissue properties.^3,4 Recent reviews^5,6 outline the methodology and clinical applications of DTI.In clinical practice, these parameters can be used for comparison between individual patients, for serial examinations in the same patient, and for the evaluation of maturation during childhood. The quantification of diffusion can be especially helpful, because it may allow earlier diagnosis of the presence and extent of pathology. Pathologic changes due to damage in the central nervous system start at the microstructural level. Previous studies have shown that changes in diffusion characteristics (ie, diffusivity and diffusion anisotropy) can be detected in stroke⁷ and multiple sclerosis⁸ before abnormalities can be detected with conventional MR imaging.^7,9,10The assessment of the variability of DTI measurements, both when the data are analyzed repeatedly by one reviewer or by different reviewers, is an essential and important step in evaluating the clinical utility of DTI and its strength as a quantitative measurement. We sought to provide measurements of the intrarater and interrater variability for DTI measurements and to assess the degree of difference that can be detected comparing 2 DTI studies.     

脑高级别星形细胞瘤瘤周DTI参数的测定及分析

目的：应用弥散张量成像（DTI）技术探讨脑高级别星形细胞瘤瘤周弥散各向异性特点。方法：25例脑高级别星形细胞瘤术前行DTI扫描,测定瘤周脑实质区及对侧正常脑实质的平均弥散系数（MD）值及各向异性分数（FA）值。并通过弥散张量纤维束成像（DTT）观察病灶与白质纤维束的关系。结果：高级别星形细胞瘤瘤周MD值为1．610±0．23,高于对侧正常脑实质（P〈0．01）。FA值为0．236±0．06,低于对侧正常脑实质（P〈0．01）。结论：DTI能够准确反应脑星形细胞瘤瘤周各向异性特点,DTT能够较为准确显示病灶与白质纤维束的关系。     

MR diffusion tensor imaging of white matter tract disruption in stroke at 3 T

Recent advances in MR diffusion weighted imaging (DWI) enable the identification of anisotropic white matter tracts with diffusion tensor imaging (DTI). We aimed to use a novel DTI technique to safely study patients with recent stroke in a high field (3 T) MR machine with its intrinsically higher spatial resolution and signal-to-noise ratio. Of ten patients studied, six had disruption of white matter tracts as determined by DTI. A further patient had distortion of white matter tracts around an infarct rather than actual disruption of the tracts themselves. The lack of tract destruction may imply a beneficial prognosis, information that is not available with conventional DWI.     

Diffusion tensor imaging to guide surgical planning in intramedullary spinal cord tumors in children

Introduction

Intramedullary spinal cord neoplasms (ISCN) in children provide diagnostic, treatment and management dilemmas. Resection results in the best chance for disease control, but the greatest risk of neurologic deficit. We hypothesize that diffusion tensor imaging (DTI) and diffusion tensor-fiber tracking (DT-FT) can help characterize margins of pediatric ISCN to aid in surgical planning.

Methods

This HIPAA compliant retrospective study was performed after Institutional Review Board approval. Patients with ISCN from a single tertiary care pediatric institution were identified, and patients with preoperative DTI were evaluated.

Results

Ten patients (eight males and two females) with ISCN with preoperative DTI were identified. The mean age was 11.1?±?6.2 years (range, 2–18 years). Eight tumors demonstrated DTI and DT-FT evidence of splayed cord tracts, and two demonstrated evidence of infiltration of cord tracts. The eight patients with splayed tracts underwent resection, with seven achieving gross-total resection and one subtotal resection. The two patients with infiltration of white matter tracts underwent biopsy of their lesion.

Conclusions

DTI of pediatric ISCN can aid in defining the margins of the tumor and relationship to the intrinsic white matter structures of the spinal cord. Splaying and displacement of fiber tracts appears to predict a discrete margin to the tumor and resectability, whereas infiltration of the white matter tracts suggests biopsy may be more advisable.     

Does the use of hormonal contraceptives cause microstructural changes in cerebral white matter? Preliminary results of a DTI and tractography study

Objective

To evaluate the effect of monophasic combined oral contraceptive pill (COCP) and menstrual cycle phase in healthy young women on white matter (WM) organization using diffusion tensor imaging (DTI).

Methods

Thirty young women were included in the study; 15 women used COCP and 15 women had a natural cycle. All subjects underwent DTI magnetic resonance imaging during the follicular and luteal phase of their cycle, or in different COCP cycle phases. DTI parameters were obtained in different WM structures by performing diffusion tensor fibre tractography. Fractional anisotropy and mean diffusivity were calculated for different WM structures. Hormonal plasma concentrations were measured in peripheral venous blood samples and correlated with the DTI findings.

Results

We found a significant difference in mean diffusivity in the fornix between the COCP and the natural cycle group. Mean diffusivity values in the fornix were negatively correlated with luteinizing hormone and estradiol blood concentrations.

Conclusion

An important part in the limbic system, the fornix, regulates emotional processes. Differences in diffusion parameters in the fornix may contribute to behavioural alternations related to COCP use. This finding also suggests that the use of oral contraceptives needs to be taken into account when designing DTI group studies.

Key Points

? Diffusion tensor MRI offers new insights into brain white matter microstructure. ? The effects of oral hormonal contraception were examined in young women. ? Diffusion tensor images and hormone blood concentrations were evaluated. ? Women using hormonal contraception demonstrated higher mean diffusivity in the fornix. ? These changes may contribute to behavioural alternations related to contraception use.     

Evaluation of brain in myotonic dystrophy using diffusion tensor MR imaging

In many cases of myotonic dystrophy, high-intensity areas are seen in the cerebral white matter on T2-weighted imaging. Brain MRI was performed in 15 patients with myotonic dystrophy using diffusion tensor imaging, which is sensitive to the detailed structure of white matter, and the results were compared with those of normal controls. FA (anisotropic diffusion) values in the cerebral white matter of myotonic dystrophy patients were significantly lower than those of normal controls (p< 0.01), even if the hyperintense lesion was not seen on T2-weighted imaging. Values of trace (isotropic diffusion) in myotonic dystrophy patients were significantly higher than those of normal controls (p< 0.05), except in the posterior limb of the internal capsule. Diffusion tensor imaging could detect pathological change of the cerebral white matter in myotonic dystrophy patients, and may be useful for quantification and detection of subtle pathological change.     

Characteristics of Diffusional Kurtosis in Chronic Ischemia of Adult Moyamoya Disease: Comparing Diffusional Kurtosis and Diffusion Tensor Imaging

BACKGROUND AND PURPOSE:Detecting microstructural changes due to chronic ischemia potentially enables early identification of patients at risk of cognitive impairment. In this study, diffusional kurtosis imaging and diffusion tensor imaging were used to investigate whether the former provides additional information regarding microstructural changes in the gray and white matter of adult patients with Moyamoya disease.MATERIALS AND METHODS:MR imaging (diffusional kurtosis imaging and DTI) was performed in 23 adult patients with Moyamoya disease and 23 age-matched controls. Three parameters were extracted from diffusional kurtosis imaging (mean kurtosis, axial kurtosis, and radial kurtosis), and 4, from DTI (fractional anisotropy, radial diffusivity, mean diffusivity, and axial diffusivity). Voxelwise analysis for these parameters was performed in the normal-appearing brain parenchyma. The association of these parameters with neuropsychological performance was also evaluated.RESULTS:Voxelwise analysis revealed the greatest differences in fractional anisotropy, followed, in order, by radial diffusivity, mean diffusivity, and mean kurtosis. In patients, diffusional kurtosis imaging parameters were decreased in the dorsal deep white matter such as the corona radiata and superior longitudinal fasciculus (P < .01), including areas without DTI abnormality. Superior longitudinal fasciculus fiber-crossing areas showed weak correlations between diffusional kurtosis imaging and DTI parameters compared with tissues with a single-fiber direction (eg, the corpus callosum). Diffusional kurtosis imaging parameters were associated with general intelligence and frontal lobe performance.CONCLUSIONS:Although DTI revealed extensive white matter changes, diffusional kurtosis imaging additionally demonstrated microstructural changes in ischemia-prone deep white matter with abundant fiber crossings. Thus, diffusional kurtosis imaging may be a useful adjunct for detecting subtle chronic ischemic injuries.

Moyamoya disease (MMD) is characterized by compensatory development of enlarged and weak basal perforating arteries (Moyamoya vessels) due to bilateral occlusive changes in the internal carotid system.¹ In addition to cerebral ischemia and intracranial hemorrhage, patients with MMD demonstrate neurocognitive issues, such as executive dysfunction, attention deficits, and working-memory disturbances.^2,3 Brain atrophy may explain cognitive impairment in the absence of infarction, but detection of these changes has been hampered by the limited sensitivity of conventional neuroimaging methods. Diffusion tensor imaging is useful for determining white matter integrity and providing parameters sensitive to changes in axons, myelin, and organelle structures.^4,5 Indeed, DTI analysis has revealed a widespread decline in white matter integrity in the normal-appearing brain with MMD.³ Thus, DTI can detect early-stage ischemic injury, which potentially predicts future cognitive outcomes. However, DTI is constrained by technical insufficiencies: It is based on the assumption that water molecules diffuse freely and that diffusion can be characterized by a Gaussian distribution.⁵In addition, the tensor model is based on the observation that in many tissues, water diffusion is anisotropic (ie, the diffusion is more liberal in some directions and more restricted in others). This anisotropic diffusion can be geometrically depicted as an ellipsoid, described by eigenvectors and eigenvalues. This model performs well in regions where fibers are aligned along a single axis. However, it fails in regions with several fiber populations aligned along intersecting axes because it cannot simultaneously map several diffusion maxima.⁶ Furthermore, because hypoxic-ischemic injury induces neurodegeneration and regression of dendrite arborization in gray matter, the diffusion properties of gray matter may also reveal the early stages of ischemic injury.^7,8 Nevertheless, analyzing isotropic or near-isotropic tissue such as gray matter by DTI may not be valid because its major parameter, fractional anisotropy (FA), reflects structure only if it is spatially oriented.⁶ A more recent method called diffusional kurtosis imaging (DKI) quantifies the deviation of water molecule diffusion from the Gaussian distribution without assuming any specific diffusion model.^6,9 Its parameters are thought to represent the complexity of tissue microstructure.⁶ Previous studies have suggested that DKI is sufficiently sensitive to detect age-related alterations in white matter microstructure.^10,11 Furthermore, measurements of diffusion anisotropy by DKI can reveal sex-related and pathologic changes in gray matter.^12,13 Thus, using DKI to evaluate the diffusion properties of gray matter and white matter in patients with MMD may be useful for detecting subtle microstructural changes due to ischemia.Diffusional kurtosis has been investigated to explore tissue reversibility in acute cerebral infarction.^14–16 However, there is a paucity of information regarding the microstructural properties measured by DKI in chronic ischemia in living humans. To expand on our prior DTI study, we investigated whether adults with MMD and no overt cerebral infarctions have altered diffusional kurtosis in the entire cerebrum. An exploratory voxel-based whole-brain analysis was performed to map regional DKI parameters and to compare DKI and DTI parameters. We also explored correlations of diffusion parameters with measures of neurocognitive impairment in an ROI analysis.