Apparent diffusion tensor measurements in myelin-deficient rat spinal cords.

The apparent diffusion tensor (ADT) was measured in excised and fixed spinal cords from myelin-deficient (md) rats and age-matched controls. These data were used to obtain the principal diffusivities of the ADT, and also the scalar invariant parameters _D (averaged principal diffusivity) and A(sigma) (anisotropy index) for four white matter and two gray matter regions. The results for white matter regions showed that the principal diffusivities were significantly higher for md animals, and while the _D was increased in tissue from md animals, the A(sigma) was found to be decreased. Grey matter _D was measured to be between those of white matter from control and md animals, and the A(sigma) was much smaller than that of white matter from both sets of animals, indicating that diffusion in md white matter is more anisotropic than in gray matter. The results show that while myelination is not a prerequisite for diffusion anisotropy, it does influence the magnitude of the observed anisotropy. Magn Reson Med 45:191-195, 2001.     

Diffusion tensor tractography as a supplementary tool to conventional MRI for evaluating patients with myelopathy

Purpose

The aim of this study was to assess the clinical utility of DTI including apparent diffusion coefficient (ADC), fractional anisotropy (FA), in patients with symptoms of spinal cord myelopathy.

Patients and methods

Fifteen subjects with clinical symptoms of acute (n = 3) or slowly progressive (n = 12) spinal cord myelopathy and 11 healthy volunteers were prospectively selected. They all underwent magnetic resonance imaging of the spine at 3.0 T machine. In addition to conventional MRI, DTI was performed; maps of the apparent diffusion coefficient and of fractional anisotropy were reconstructed. Diffusion tensor tractography was used to visualize the morphological features of normal and impaired white matter at the level of the pathological lesions in the spinal cord. The patients were divided into two groups according to the signal intensity on T2WI (group A with no change in signal intensity and group B with high signal intensity).

Results

There were no statistically significant differences in the apparent diffusion coefficient and fractional anisotropy values between the different spinal cord segments of the normal subjects. All of the patients in group B had increased apparent diffusion coefficient values and decreased fractional anisotropy values at the lesion level compared to the normal controls. However, there were no statistically significant diffusion index differences between group A patients and the normal controls.

Conclusion

Diffusion tensor imaging is a reliable method for the evaluation of the diffusion properties of normal and compressed spinal cords. Furthermore, this technique can be used as an important supplementary tool to conventional MRI for the quantification of fiber damage in spinal cord compression, thus has the potential to be of great utility for treatment planning and follow up.     

Diffusion anisotropy MRI for quantitative assessment of recovery in injured rat spinal cord.

Spinal cord injury and its devastating consequences are the subject of intensive research aimed at reversing or at least minimizing functional loss. Research efforts focus on either attenuating the post-injury spread of damage (secondary degeneration) or inducing some regeneration. In most of these studies, as well as in clinical situations, evaluation of the state of the injured spinal cord poses a serious difficulty. To address this problem, we carried out a diffusion-weighted MRI experiment and developed an objective routine for quantifying anisotropy in injured rat spinal cords. Rats were subjected to a contusive injury of the spinal cord caused by a controlled weight drop. Untreated control rats were compared with rats treated with T cells specific to the central nervous system self-antigen myelin basic protein, a form of therapy recently shown to be neuroprotective. After the rats were killed their excised spinal cords were fixed in formalin and imaged by multislice spin echo MRI, using two orthogonal diffusion gradients. Apparent diffusion coefficient (ADC) values and anisotropy ratio (AI) maps were extracted on a pixel-by-pixel basis. The calculated sum of AI values (SAI) for each slice was defined as a parameter representing the total amount of anisotropy. The mean-AI and SAI values increased gradually with the distance from the site of the lesion. At the site itself, the mean-AI and SAI values were significantly higher in the spinal cords of the treated animals than in the controls (P = 0.047, P = 0.028, respectively). These values were consistent with the score of functional locomotion. The difference was also manifested in the AI maps, which revealed well-organized neural structure in the treated rats but not in the controls. The SAI values, AI histograms, and AI maps proved to be useful parameters for quantifying injury and recovery in an injured spinal cord. These results encourage the development of diffusion anisotropy MRI as a helpful approach for quantifying the extent of secondary degeneration and measuring recovery after spinal cord injury. Magn Reson Med 45:1-9, 2001.     

Diffusion-prepared fast imaging with steady-state free precession (DP-FISP): a rapid diffusion MRI technique at 7 T

Diffusion MRI is a useful imaging technique with many clinical applications. Many diffusion MRI studies have utilized echo-planar imaging (EPI) acquisition techniques. In this study, we have developed a rapid diffusion-prepared fast imaging with steady-state free precession MRI acquisition for a preclinical 7T scanner providing diffusion-weighted images in less than 500 ms and diffusion tensor imaging assessments in ～1 min with minimal image artifacts in comparison with EPI. Phantom apparent diffusion coefficient (ADC) and fractional anisotropy (FA) assessments obtained from the diffusion-prepared fast imaging with steady-state free precession (DP-FISP) acquisition resulted in good agreement with EPI and spin echo diffusion methods. The mean apparent diffusion coefficient was 2.0 × 10(-3) mm(2) /s, 1.90 × 10(-3) mm(2) /s, and 1.97 × 10(-3) mm(2) /s for DP-FISP, diffusion-weighted spin echo, and diffusion-weighted EPI, respectively. The mean fractional anisotropy was 0.073, 0.072, and 0.070 for diffusion-prepared fast imaging with steady-state free precession, diffusion-weighted spin echo, and diffusion-weighted EPI, respectively. Initial in vivo studies show reasonable ADC values in a normal mouse brain and polycystic rat kidneys.     

Diffusion time dependence of the apparent diffusion tensor in healthy human brain and white matter disease.

The diffusion time dependence of the brain water diffusion tensor provides information regarding diffusion restriction and hindrance but has received little attention, primarily due to limitations in gradient amplitude available on clinical MRI systems, required to achieve short diffusion times. Using new, more powerful gradient hardware, the diffusion time dependence of tensor-derived metrics were studied in human brain in the range 8-80 ms, which encompasses the shortest diffusion times studied to date. There was no evidence for a change in mean diffusivity, fractional anisotropy, or in the eigenvalues with diffusion time in healthy human brain. The findings are consistent with a model of unrestricted, but hindered water diffusion with semipermeable membranes, likely originating from the extracellular space in which the average extracellular separation is less than 7 microns. Similar findings in two multiple sclerosis plaques indicated that the size of the water diffusion space in the lesion did not exceed this dimension.     

Diffusion tensor imaging of in vivo and excised rat spinal cord at 7 T with an icosahedral encoding scheme.

Regional values of fractional anisotropy (FA) and mean diffusivity (D(av)) of in vivo and excised rat spinal cords were measured using an iscosahedral encoding scheme that is based on 21 uniformly distributed and alternating gradient directions with an echo planar imaging (EPI) readout. Based on the water phantom studies, this scheme was shown to provide unbiased estimation of FA. The stability of the scanner during the acquisition of diffusion tensor imaging (DTI) data was evaluated. Repeated measurements of the FA values demonstrated excellent reproducibility, as assessed by the Bland-Altman analysis. These studies demonstrated a reduced anisotropy in excised samples relative to in vivo cords. Diffusion in the spinal cord gray matter was shown to be anisotropic. The FA value in the dorsal white matter (WM) was found to be higher relative to the ventral WM. Results from these studies should provide the necessary baseline data for serial in vivo DTI of injured spinal cord.     

In vivo diffusion tensor imaging of the rat spinal cord at 9.4T

PURPOSE: To determine differences in diffusion measurements in white matter (WM) and gray matter (GM) regions of the rat cervical, thoracic, and cauda equina spinal cord using in vivo diffusion tensor imaging (DTI) with a 9.4T MR scanner. MATERIALS AND METHODS: DTI was performed on seven rats in three slices at the cervical, thoracic, and cauda equina regions of the spinal cord using a 9.4T magnet. Axial diffusion weighted images (DWIs) were collected at a b-value of 1000 seconds/mm(2) in six directions. Regions of interest were identified via T2-weighted images for the lateral, dorsal, and ventral funiculi, along with GM regions. RESULTS: Analysis of variance (ANOVA) results indicated significant differences between every WM funiculus compared to GM for longitudinal apparent diffusion coefficient (lADC), transverse apparent diffusion coefficient (tADC), fractional anisotropy (FA), measured longitudinal anisotropy (MA1), and anisotropy index (AI). A significant difference in mean diffusivity (MD) between regions of the spinal cord was not found. Diffusion measurements were significantly different at each spinal level. In general, GM regions were significantly different than WM regions; however, there were few significant differences between individual WM regions. CONCLUSION: In vivo DTI of the rat spinal cord at 9.4T appears sensitive to the architecture of neural structures in the rat spinal cord and may be a useful tool in studying trauma and pathologies in the spinal cord.     

Diffusion tensor tractography demonstration of partially injured spinal cord tracts in a patient with posttraumatic Brown Sequard syndrome

The authors report the utility of diffusion tensor tractography in demonstrating the partially severed spinal cord tracts on one side with normal, intact, distally traceable tracts on the opposite side in a patient with posttraumatic Brown Sequard syndrome. A 30-year-old man presented with typical clinical features of a hemisection injury of the thoracic spinal cord, 2 months after he had sustained a back stab injury. Routine MRI showed T2 hyperintense zones in the thoracic spinal cord at the level of T5. We did axial single shot echo planar diffusion tensor imaging with a 1.5 Tesla MR machine. Tractography effectively depicted the injured spinal cord tracts on the left side with normal intact tracts on the right side, which could be traced distally. The fractional anisotropy and apparent diffusion coefficient values showed significant changes at the level of injury. Tractographic demonstration of human spinal cord injury is reported for the first time.     

快速 DTI 在急性颈髓损伤的临床应用

目的：研究扩散张量成像(DTI)在急性颈髓损伤(CSCI)的成像特点,评估其临床应用价值。方法本组8例 CSCI 患者(发病72 h 内)均采用3.0T 磁共振仪进行快速颈髓 DTI 扫描,并在工作站进行扩散张量纤维束成像(DTT)。同时,在工作站分别测量并计算颈髓病变区及上下相对正常区的各向异性(FA)值和表观扩散系数(ADC)值,之后进行统计学组间配对 t 检验分析(SPSS 13.0)。结果急性 CSCI 以 C5~C6节段(占4/8)和 C4~C5节段(占3/8)多见,且快速 DTI 均获得了较好的图像质量。急性 CSCI 时病变区 FA 值和 ADC 值均明显低于相对正常区域数值(P <0.01),相应在 FA 图和 ADC 图均表现为低信号,而上下相对正常区 FA 值和 ADC 值间无明显区别;同时,DTT 有利于显示刀刺伤导致的颈髓纤维束断裂,颈髓闭合伤则主要表现为脊髓纤维束紊乱等。结论3.0T 快速 DTI 序列可以在2 min 扫描时间内获得临床较为满意的诊断图像,并通过 FA 值和 ADC 值更敏感地反映急性 CSCI 后髓鞘损伤导致的 FA 改变及细胞毒性水肿和血管源性水肿导致的水分子扩散的变化。     

Changes in brain water diffusion during childhood

We studied the changes in brain water diffusion in childhood as seen on diffusion-weighted MRI in 30 children from 1 day of life to 17 years to provide a data base and to investigate the correlation of diffusion changes with known patterns of white matter maturation. The apparent diffusion coefficient (ADC) and apparent anisotropy (AA) were calculated in numerous regions of the brain to include major white matter tracts and gray matter. ADC and AA values were directly related to the structural maturity and compactness of the white matter tracts and changed with aging in a way that predated early myelination markers such as signal change on T1- or T2-weighted images. Diffusion of water is sensitive to structural changes in the brain such as white matter maturation and may be useful in investigating white matter disorders. Received: 18 March 1999 Accepted: 25 March 1999     

A quantitative analysis of the benefits of cardiac gating in practical diffusion tensor imaging of the brain

Increasing demand for quantitative diffusion MRI in biomedical research necessitates a reevaluation of potential sources of artifact. While cardiac pulsation–induced effects have been reported previously, their quantitative characterization under standard acquisition protocols remains outstanding. To determine whether practical data quality improvements merit the use of cardiac gating, the maximum effects induced in apparent diffusion coefficient, fractional anisotropy, and mean diffusivity measurements were quantitatively estimated via measurements and bootstrapping simulations. In apparent diffusion coefficient time courses, cardiac pulsation effects were measured to occupy approximately 6% of the heartbeat duration, with considerable intersession differences in effect magnitude. Bootstrapping revealed overestimations in fractional anisotropy up to 0.26, and mean diffusivity up to 0.19 × 10^?3 mm² sec^?1 without gating compared to 0.072 (fractional anisotropy) and 0.043 × 10^?3 mm² sec^?1 (mean diffusivity) in the same gated simulation. However, while cardiac pulsation may thus impair the quantification of fractional anisotropy and mean diffusivity in some individuals, our data suggested negligible effects in group studies. Magn Reson Med 63:1098–1103, 2010. © 2010 Wiley‐Liss, Inc.     

Intracellular volume and apparent diffusion constants of perfused cancer cell cultures,as measured by NMR

Diffusion NMR spectroscopy was used to study intracellular volume and apparent water diffusion constants in different cell lines (DU145, human prostate cancer; AT3, rat prostate cancer; MCF-7, human breast cancer; RIF-1, mouse fibrosacroma). The cells were grown on various matrices (collagen sponge, collagen beads, polystyrene beads) which enabled continuous growth in perfused high density cell culture suitable for NMR studies. In perfused cell systems, the attenuation of the water signal versus the squared gradient strength was fitted by the sum of two decaying exponentials. For the slowly decaying component the apparent water diffusion constant at 37°C was 0.22 (±0.02) × 10^?9 s/m² for all cell lines at diffusion times > 100 ms. It continuously increased up to 0.47(±0.05) × 10^?9 s/m² when the diffusion time was decreased to 8 ms, indicating restricted diffusion. No significant effect of the matrices was observed. The fractional volume of the slow component as determined from the biexponential diffusion curve correlated with the relative intracellular volume, as obtained from the cell density in the sample and the cell size as measured by light microsocopy. Therefore, this simple NMR approach can be used to determine intracellular volume in perfused cell cultures suitable for NMR studies. Using this information in combination with spectroscopic data, changes in intracellular metabolite concentration can be detected even when the cellular volume is changing during the experiment. The apparent diffusion constant for the fast diffusing component varied with growth matrix, cell density and cell type and also showed the typical characteristics of restricted diffusion (increase of apparent diffusion constant with time).     

Ex vivo diffusion tensor imaging and quantitative tractography of the rat spinal cord during long-term recovery from moderate spinal contusion

Purpose

To characterize DTI metric changes throughout the length of the entire spinal cord from the acute through chronic stages of spinal cord injury (SCI).

Materials and Methods

Ex vivo DTI was performed at 9.4 Tesla to examine changes in water diffusion throughout the entire spinal cord (7‐cm) up to 25 weeks after injury in a rat model of contusive SCI. Animals were grouped according to recovery times after injury (2, 5, 15, 20, or 25 weeks), and various DTI metrics were evaluated including transverse and longitudinal apparent diffusion coefficient (tADC and lADC), mean diffusivity (MD), and fractional anisotropy (FA).

Results

An overall decrease in lADC throughout the cord and decreases in MD remote from the lesion site were observed, along with an increase in tADC within fiber tracts throughout the recovery period. These trends were statistically significant at P < 0.05 and were found in both white and gray matter regions. tADC and lADC distributions in fiber bundles extracted using DTI tractography were well fit by an exponential model (R = 0.998) with time constants of 4.6 and 3.3 days, respectively.

Conclusion

Results from the current study support the hypothesis that the spinal cord undergoes continual changes during recovery from SCI. J. Magn. Reson. Imaging 2008;28:1068–1079. © 2008 Wiley‐Liss, Inc.     

Extending the range of diffusion times for regional measurement of the 3He ADC in human lungs.

A stimulated-echo-based technique was developed to measure the regional apparent diffusion coefficient (ADC) of hyperpolarized 3He during a single breathhold for diffusion times of 25 ms or greater. Compared to previous methods, a substantially shorter minimum diffusion time was achieved by decoupling diffusion sensitization from image acquisition. A hyperpolarized-gas phantom was used to validate the method, which was then tested in four healthy subjects in whom regional ADC maps were acquired with diffusion times of 50, 200, and 1500 ms and a tag wavelength of 5 or 10 mm. ADC values from healthy subjects were in good agreement with reported literature values and decreased with increasing diffusion time. Mean ADC values were approximately 0.07, 0.03, and 0.015 cm2/s for diffusion times of 50, 200, and 1500 ms, respectively. ADC maps were generally homogeneous, with similar mean values when measured with the same parameters in different subjects.     

3T MRI腰骶部脊神经根扩散张量成像在腰椎间盘突出症中的应用价值

目的 探索扩散张量成像(diffusion tensor imaging,DTI)和纤维示踪成像(fibre tracking,FT)显示腰骶脊神经根的可行性,并评估椎间盘突出症患者L4及L5脊神经根各向异性分数(fractional anisotropy,FA)和表观扩散系数(apparent diffusion coefficient,ADC)值的差别.方法 20例由于后外侧或椎间孔椎间盘突出引起单侧坐骨神经痛的患者和20例健康志愿者纳入研究.所有检查均在Philips Achieve 3.0 T TX MRI上进行,纤维示踪成像参数:FA阈值＝0.15;最小纤维束长度=10mm;最大角度=27°.应用横轴位T2解剖融合图像序列评估重建图像的相关性.对所有被检者的L4、L5和S1脊神经根行扩散张量和纤维示踪成像,并在FA图和ADC图上测量L4和L5脊神经根的平均FA值和ADC值.结果 腰椎间盘突出症患者和健康志愿者腰骶部脊神经根纤维束成像在T2解剖融合图像上完全匹配.在纤维示踪图像上可以清晰地辨别腰骶部脊神经根受压位置.所有患者和健康志愿者的FA值和ADC值可以从FA图和ADC图上获得.受压侧脊神经根的FA值显著低于对侧神经根(P＜0.01)和健康志愿者的(P＜0.01); ADC值显著高于对侧神经根(P＜0.01)和健康志愿者的(P＜0.01).结论 3T MRI腰骶部脊神经根扩散张量和纤维示踪成像是可行的.腰椎间盘突出症患者受压L4和L5脊神经根的FA值和ADC值有显著性的变化.     

Diffusion imaging concepts for clinicians

This review covers the fundamentals of diffusion tensor imaging. It is written with the clinician in mind and assumes the reader has a passing familiarity with magnetic resonance imaging (MRI). Topics covered include comparison of diffusion MRI with conventional MRI, water apparent diffusion coefficient (ADC), diffusion anisotropy, tract tracing, and changes of water apparent diffusion in response to injury. The discussion centers primarily on applications to the central nervous system, but examples from other tissues are included.     

Visualization of neural tissue water compartments using biexponential diffusion tensor MRI.

The apparent diffusion tensor (ADT) imaging method was extended to account for multiple diffusion components. A biexponential ADT imaging experiment was used to obtain separate images of rapidly and slowly diffusing water fractions in excised rat spinal cord. The fast and slow component tensors were compared and found to exhibit similar gross features, such as fractional anisotropy, in both white and gray matter. However, there were also some important differences, which are consistent with the different structures occupying intracellular and extracellular spaces. Evidence supporting the assignment of the two tensor components to extracellular and intracellular water fractions is provided by an NMR spectroscopic investigation of homogeneous samples of brain tissue. Magn Reson Med 45:580-587, 2001.     

弥漫性轴索损伤患者胼胝体DTI纵向评估

目的 评价亚急性期弥漫性轴索损伤(DAI)患者胼胝体各亚区域微观结构及其短期变化.方法 连续性纳入亚急性期DAI患者21例,其中12例于1月后(31.5 d±6.2 d,28~43 d)复查,招募12例性别、年龄匹配的健康对照组,所有受试者使用3.0T磁共振仪扫描获取脑部DTI数据.在矢状位各向异性分数(FA)图将胼胝体分为6个亚区域(胼胝体膝部、体嘴部、体前部、体后部、峡部及压部)计算FA值、表观扩散系数(ADC)值,分析亚急性期和随访患者胼胝体DTI参数变化,并将亚急性期患者胼胝体各亚区域DTI参数与入院时格拉斯哥(GCS)评分做相关分析.结果 亚急性期患者整个胼胝体及所有亚区域FA值显著降低,除胼胝体体前部、体后部外其余亚区域ADC值均显著升高(P<0.05),其中胼胝体峡部FA值下降幅度最大(-12.0%).12例随访患者整个胼胝体及各亚区域FA值和ADC值变化均无统计学意义(P>0.05).亚急性期患者整个胼胝体、峡部及压部FA值与入院时GCS评分呈正相关(整个胼胝体:r=0.848,P=0.000;峡部:r=0.447,P=0.048;压部:r=0.591,P=0.006).结论 胼胝体峡部是DAI最易损伤的部位;短期内(1个月)胼胝体亚区域微观结构无显著变化;亚急性期DAI患者整个胼胝体FA值能较好反映DAI患者损伤程度.     

Mapping of (3) He apparent diffusion coefficient anisotropy at sub-millisecond diffusion times in an elastase-instilled rat model of emphysema

Hyperpolarized (3) He gas can provide detailed anatomical maps of the macroscopic airways in the lungs (i.e., ventilation) as well as insight into the lung microstructure through the apparent diffusion coefficient. In particular, the apparent diffusion coefficient of (3) He in the lung exhibits anisotropic effects that depend on diffusion time (δ), and it has been shown to be extraordinarily sensitive to enlargement in terminal airways and alveoli associated with emphysema. In this study, the anisotropic nature of the (3) He apparent diffusion coefficient is studied in a rat model of emphysema, based on elastase instillation, specifically for δ values less than one millisecond. Longitudinal (D(L) ) and transverse (D(T) ) diffusion coefficients were mapped at δ = 360 μs and δ = 800 μs based on a cylinder model of lung structure and correlated with histological measurement of alveolar damage based on mean linear intercept (L(m) ). Whole-lung mean D(T) measured at δ = 360 μs in the elastase-instilled rat lungs (0.14 ± 0.09 cm(2) /s) demonstrated the most significant increase (p = 0.00195) compared to the sham-instilled cohort (0.06 ± 0.06 cm(2) /s) and had a strong linear correlation with L(m) (Pearson's correlation coefficient of 0.9). These results suggest that measurement of (3) He apparent diffusion coefficient anisotropy, specifically D(T) , can provide a sensitive indicator of emphysema, particularly at very short diffusion times (δ = 360 μs).