Quantitative evaluation of the pyramidal tract segmented by diffusion tensor tractography: feasibility study in patients with amyotrophic lateral sclerosis

PURPOSE: Diffusion tensor imaging can evaluate the cerebral white matter quantitatively using fractional anisotropy (FA) and also can extract a certain tract by tractography, but these two have been used separately and not combined. The purpose of this study was to assess the clinical feasibility of ROI analysis using diffusion tensor tractography (DTT) in patients with amyotrophic lateral sclerosis (ALS). MATERIALS AND METHODS: Sixteen patients with ALS (9 limb-onset type, 7 bulbar-onset type) and nine age-matched volunteers were studied. DTT of the corticobulbar tract (DTT-CBT) and corticospinal tract (DTT-CST) were visualized by free software (dTV/VOLUME-ONE). Regions-of-interest (ROIs) were semi-automatically placed on the tracts defined by DTT methods, and FA values within the ROIs were measured. RESULTS: Mean FA values of ALS patients in the ROIs along the DTT-CST (bulbar-onset: 0.574, limb-onset: 0.594) were significantly lower than those of controls (DTT-CST: 0.629) (p<0.05). The mean FA of DTT-CBT of the bulbar-onset type (0.509) was significantly lower than that of the limb-onset type (0.558) and that of volunteers (0.561). CONCLUSION: DTT could segmentate certain white matter tracts and evaluate them quantitatively. It could depict the subtle changes between subtypes of ALS as well as the changes between the patients and volunteers.     

The corticospinal tract in amyotrophic lateral sclerosis: An MRI study

Cortical motor neurone loss and corticospinal tract (CST) degeneration are typical of amyotrophic lateral sclerosis (ALS). It is a matter of debate whether qualitative assessment of the CST by MRI is useful in the diagnosis. It is also an open question whether quantitative determination of the T2 relaxation times can improve its value. Signal intensity along the CST on 14 consecutive slices was assessed using arbitrary visual rating on double-echo T2-weighted and proton-density spin-echo images of 21 patients with ALS and 21 age- and sex-matched controls. T2 was determined quantitatively. On the T2-weighted images the patients' ratings did not differ from that of controls. The T2 of patients and controls showed no statistical difference in any slice. There was no correlation between T2 and patient age, duration of the disease, or predominant bulbar, lower or upper motor neurone signs. The only correlation between MRI findings and disease was on the proton-density images: all cases in which the CST was poorly seen were controls; a clearly high-signal CST was seen only in the patients. High conspicuity of the CST was thus specific but not sensitive for the diagnosis of ALS. T2-weighted images and measurement of T2 were not useful for diagnosis. Received: 20 January 1997 Accepted: 4 June 1997     

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.     

Mapping of iron deposition in conjunction with assessment of nerve fiber tract integrity in amyotrophic lateral sclerosis

Purpose:

To test if and where increased iron accumulation occurs in amyotrophic lateral sclerosis (ALS) by quantitative mapping of iron deposition and to relate these findings to white matter tract degeneration assessed by diffusion tensor imaging (DTI).

Materials and Methods:

Fifteen patients with ALS and 15 age‐ and gender‐matched controls underwent MRI of the brain to obtain R₂* relaxation rate and DTI measurements, focusing on the corticospinal tract (CST) and on deep gray matter structures, using tract‐based spatial statistics (TBSS).

Results:

Compared with controls, ALS patients showed reduced fractional anisotropy values along the mesencephalic CST, suggesting disintegration of fiber tracts. A trend for R₂* values to be elevated was found in the CST of ALS patients. Regarding other brain areas examined, increased R₂* values in ALS patients were observed solely in the caudate nucleus.

Conclusion:

This study extends previous findings on fiber disorganization by additional quantitative evidence for increased iron deposition in closely localized regions along the CST in ALS patients. Longitudinal studies are needed to further explore the pathophysiologic and diagnostic implications of these findings. J. Magn. Reson. Imaging 2010;31:1339–1345. © 2010 Wiley‐Liss, Inc.     

Diffusion tensor imaging in amyotrophic lateral sclerosis: volumetric analysis of the corticospinal tract

BACKGROUND AND PURPOSE: Diffusion tensor imaging (DTI) allows direct visualization and volumetric analysis of the corticospinal tract (CST). The purpose of this study was to determine whether color maps and fiber tracking derived from DTI data are valuable in detecting and quantifying CST degeneration in patients with amyotrophic lateral sclerosis (ALS). METHODS: Sixteen patients with ALS with clinical signs of upper motor neuron (UMN) involvement and 17 healthy subjects were studied with the use of DTI. Disease severity was determined by means of the ALS Functional Rating Scale-Revised (ALSFRS-R) and an UMN involvement score. DTI was acquired with a 12-direction, single-shot, spin-echo echo-planar sequence. The CST from the lower pons to the corona radiata at the level of the corpus callosum on 4 contiguous coronal sections was manually segmented by using color maps generated from the DTI data. The left and right CST volumes were measured separately and normalized to the total intracranial volume. Normalized CST volumes were compared between patients with ALS and healthy subjects. RESULTS: The CST volumes of patients with ALS were significantly reduced (P < .01, unpaired t test) compared with healthy subjects, in both affected and nonaffected hemispheres. No significant correlation was found between CST volumes and any of the clinical parameters, including disease duration, ALSFRS-R, or UMN involvement score. CONCLUSION: This study shows that volumetric analysis by using DTI-based color maps is valuable in detecting and monitoring structural degeneration of the CST. This will lead to objective and quantitative assessment of axonal degeneration in ALS.     

Diffusion tensor imaging for long-term follow-up of corticospinal tract degeneration in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a predominantly clinical and electromyographic diagnosis. Conventional MRI reveals atrophy of the motor system, particularly the pyramidal tract, in the advanced stages but does not provide a sensitive measure of disease progression. Three patients with different principal symptoms of ALS, i.e., with predominant involvement of the upper (UMN) or lower (UMN) motor neurons, or bulbar disease, respectively, underwent serial clinical examination including lung function tests, conventional MRI, and diffusion tensor imaging (DTI). MRI demonstrated changes in of the pyramidal tract without measurable variation on follow-up. The patient with UMN involvement showed remarkable progressive loss of diffusion anisotropy in the pyramidal tract. DTI might be useful, together with clinical follow-up, as an objective morphological marker in therapeutic trials.     

Diffusion-tensor MR imaging of corticospinal tract in amyotrophic lateral sclerosis and progressive muscular atrophy

PURPOSE: To prospectively evaluate several diffusion-tensor magnetic resonance (MR) imaging indexes (mean diffusivity [MD], fractional anisotropy [FA], and eigenvalues) of corticospinal tract impairment in patients with progressive muscular atrophy (PMA) and patients with amyotrophic lateral sclerosis (ALS). MATERIALS AND METHODS: This study had institutional review board approval, and written informed consent was obtained from all subjects. Eight male patients with PMA (mean age, 63 years +/- 13 [standard deviation]), eighteen patients with ALS (14 men and four women; mean age, 64 years +/- 7), and twelve control subjects (four men and eight women; mean age, 65 years +/- 6) underwent diffusion-tensor MR imaging at which 25 spin-echo echo-planar imaging diffusion-weighted images (b = 1000 sec/mm2) were acquired along noncollinear directions. MD and FA were measured along the corticospinal tracts in each patient and subject. Changes in diffusion along and orthogonal to fiber bundles in patients were evaluated by using diffusion-tensor eigenvalues. Differences in diffusion-tensor imaging indexes between patients with PMA and those with ALS, as compared with these indexes in control subjects, were evaluated with Mann-Whitney testing. Correlations between diffusion-tensor imaging indexes and clinical variables were estimated with Pearson and Spearman rank correlation testing. RESULTS: As compared with MD (697.1 x 10(-6) mm2/sec +/- 28.1) and FA (0.585 +/- 0.032) in control subjects, MD was typically significantly increased (734.7 x 10(-6) mm2/sec +/- 41.2, P = .035) and FA significantly decreased (0.534 +/- 0.053, P = .037) along the corticospinal tracts in patients with ALS, while these parameters showed no significant change in patients with PMA (MD, 707.0 x 10(-6) mm2/sec +/- 44.2; FA, 0.559 +/- 0.028). Estimation of diffusion-tensor eigenvalues revealed normal diffusion along fiber tracts in all patients, while diffusion was increased orthogonal to fiber tracts only in patients with typical ALS. In patients with ALS, MD correlated with disease duration while FA correlated with disease severity. CONCLUSION: Diffusion-tensor MR imaging reveals corticospinal tract impairment in ALS but not in PMA.     

Motor neuron disease: primary lateral sclerosis and amyotrophic lateral sclerosis

AIM: Primary lateral sclerosis and amyotrophic lateral sclerosis are amongst motor neuron diseases. Differences between these two disorders are stressed by this paper. SOURCE OF DATA: Articles pertinent to this subject from the past 10 years. CONCLUSION: Both disorders are of neurodegenerative pathogenesis, and motor neurons are selectively involved. Unless only motor neurons from central nervous system are involved in primary lateral sclerosis, in amyotrophic lateral sclerosis motor neurons are involved both in central and in peripheral nervous system. Clinical neurophysiological and radiological features are helpful in differential diagnosis of these diseases. Primary lateral sclerosis has better prognosis and much higher survival rate.     

MR imaging of amyotrophic lateral sclerosis]

Magnetic resonance imaging (MR imaging) provides a sensitive method for mapping the normal and pathological distribution of iron in the brain. High field strength MR imaging (1.5 T) was used to evaluate eight patients with amyotrophic lateral sclerosis (ALS) and 49 neurological normal control patients. All eight ALS patients showed decreased signal intensity in the motor cortex on T2-weighted images, while only one of the normal control patients showed this finding. The results suggested that the decreased signal intensity in the motor cortex in ALS was caused by the deposition of iron in this area.     

MRI and SPECT findings in amyotrophic lateral sclerosis

Summary MRI was performed in 21 patients and single photon emission computed tomography (SPECT) withN-isopropyl-p-¹²³I iodoamphetamine in 16 patients, to visualize upper motor neurone lesions in amyotrophic lateral sclerosis. T2-weighted MRI revealed high signal along the course of the pyramidal tract in the internal capsule and cerebral peduncle in 4 of 21 patients. SPECT images were normal in 4 patients, but uptake was reduced in the cerebral cortex that includes the motor area in 11.     

MRI and clinical features in amyotrophic lateral sclerosis

MRI of the brain and spinal cord was performed in 21 patients with amyotrophic lateral sclerosis (ALS), 8 normal volunteers and 16 neurological disease controls. High signal was seen in the intracranial corticospinal tract in 16 of the 21 patients on T2-weighted and in 10 on proton density (PD)-weighted images. In one patient, the high signal on T2-weighted images became less marked with progression of the disease. Low signal intensity was seen in the motor cortex in 12 of the 21 patients. High signal in the anterolateral column of the spinal cord on T1 weighted images was seen in 14, and high signal in the lateral corticospinal tract on T2 weighted images was seen in 7 of the 21 patients. The relationship between the abnormal images and upper motor neurone signs remained unclear. High signal intensity was seen in the corticospinal tract in the brain on T2-weighted images in two normal volunteers and four disease controls, and on PD weighted images in three disease controls. Low signal intensity in the motor cortex on T2 weighted images was seen in three normal volunteers and four disease controls. However, high signal intensity was seen in the intracranial corticospinal tract on T1 weighted images in five patients with ALS who showed pronounced upper motor neurone signs including spastic paraparesis, but not in controls. Thus, abnormalities on MRI in the brain and spinal cord should be considered in the diagnosis of ALS, and high signal intensity of the intracranial corticospinal tract on T1-weighted images may reflect the severe pathological changes of the upper motor neurones in ALS. Received: 18 March 1997 Accepted: 2 May 1997     

肌萎缩侧索硬化症的~1H-MR波谱研究

目的 探讨肌萎缩侧索硬化症(ALS)患者的1H-MRS表现及其与临床评分的关系.方法 对15例临床确诊及拟诊为ALS的患者(ALS组)和15名年龄相匹配的健康志愿者(对照组)进行1H-MRS扫描,采用单体素平均TE选择性单点分辨波谱序列(TE-Averaged PRESS).扫描图像经后处理,分别获得以中央前回为中心的运动皮层和内囊后肢处的以下成分波峰:N-乙酰天门冬氨酸(NAA)、谷氨酸(Glu)、谷氨酸复合物(Glx)以及肌酸(Cr),并测量NAA/Cr、Glu/Cr和Glx/Cr峰高相对值.采用t检验比较两组间各比值的差异,并分析上述各值与ALS患者临床评分的直线相关关系.结果 ALS组运动皮层和内囊后肢的NAA/Cr值为1.91±0.34、1.53±0.17,对照分别为2.23±0.33,1.66±0.07.两组间差异有统计学意义(t值分别为4.25、2.90,P值分别为0.00、0.01).AIS组运动皮层和内囊后肢Glu/Cr为0.34±0.05、0.29±0.06,Glx/Cr为0.40±0.04、0.33±0.06,均高于对照组(Glu/Cr分别为0.30±0.03、0.25±0.04,Glx/Cr分别为0.32±0.05,0.26±0.03),两组间差异有统计学意义(t值分别为2.56、2.40、7.34、5.30,P值分别为0.02,0.03、0.00、0.00).ALS患者Norris评分值为(57±8)分,ALS功能分级评分(ALSFRS)值为(29±4)分.直线相关分析发现ALS患者运动皮层Glx/Cr值与Norris评分呈负相关(r=-0.75,P=0.00),而与ALSFRS值无相关性.结论 ALS患者谷氨酸类代谢物含量升高.(1)H-MRS可反映ALS患者脑内代谢物的变化特征.     

Digital cineradiographic study of swallowing in patients with amyotrophic lateral sclerosis

PURPOSE: This study was performed to evaluate the usefulness of digital cineradiography in detecting swallowing disorders in dysphagic patients affected by amyotrophic lateral sclerosis (ALS) with a view to planning an adequate therapeutic approach. MATERIAL AND METHODS: From January 2005 to September 2006, 23 patients (10 men and 13 women; mean age 41.3+/-8.6 years) affected by ALS were evaluated with digital cineradiography to assess the grade of dysphagia. All patients were classified using the Hillel ALS Severity Scale (ALSSS). All examinations were performed with radiocontrolled equipment provided with a digital C-arm. RESULTS: The cineradiographic technique enabled us to differentiate patients with disorders of the oral (17/23) and/or pharyngeal (19/23) swallowing phase from those without swallowing dysfunction (4/23). In 14/23 patients, passage of contrast medium into the upper airways was observed during swallowing, whereas in 5/23 cases, aspiration of contrast medium into the lower airways was recorded. CONCLUSIONS: The videofluoroscopic swallowing study has high diagnostic capabilities in the evaluation of swallowing disorders, as it is able to identify the degree and causes of impairment. In addition, the study proved useful for planning speech therapy and for follow-up in patients with ALS.     

Amyloid- and FDG-PET imaging in amyotrophic lateral sclerosis

Purpose

We aimed to study brain metabolism and presence of beta-amyloid deposits using positron emission tomography (PET) in patients with amyotrophic lateral sclerosis (ALS).

Methods

This prospective cross-sectional study included 18 patients with definite or probable ALS according to the revised El Escorial diagnostic criteria, and 24 healthy controls. Patients underwent neurological and neuropsychological assessments, PET with ¹⁸F-fluorodeoxyglucose (FDG), and amyloid-PET with ¹⁸F-florbetaben.

Results

Patients with ALS showed hypometabolism in the frontal area and hypermetabolism in the cerebellum compared to healthy controls. Four patients (22 %) displayed cognitive impairment and decreased metabolism in the frontal area extending bilaterally to the parietal regions, and increased metabolism in the posterior area of the cerebellum. In patients with no cognitive impairment, metabolism was lower in the left superior frontal gyrus and higher in the anterior and posterior lobes of the cerebellum. In the individual analysis, six patients (35 %) displayed more anterior involvement with hypometabolism affecting the superior frontal, medial, and inferior gyri; six patients (35 %) exhibited a more posterior pattern with hypometabolism in the precentral and postcentral gyri and in the superior and inferior parietal lobules; two patients (11 %) showed a mixed pattern; and three patients (17 %) showed no alterations in brain metabolism. Three (16 %) showed increased ¹⁸F-florbetaben uptake compared to controls.

Conclusions

We have identified two main patterns of brain metabolism with an association to cognitive status. Only a subgroup of patients showed an increased uptake of the amyloid tracer. Our results suggest that ALS is heterogeneous from a clinical, metabolic, and molecular standpoint.

     

Cerebral cortical and white matter lesions in amyotrophic lateral sclerosis with dementia: correlation with MR and pathologic examinations

BACKGROUND AND PURPOSE: Amyotrophic lateral sclerosis with dementia (ALSD) is a progressive neurodegenerative disorder, characterized clinically by motor neuron symptoms and dementia, and pathologically by degeneration of the motor neurons of the brain and spinal cord as well as atrophy of the frontal and/or temporal lobes. So far, there has been no study on the correlation of MR images with histologic findings in ALSD. We studied the correlation of antemortem and postmortem T2-weighted MR images with histologic findings in autopsy-proved cases of ALSD. MATERIALS AND METHODS: Antemortem and postmortem T2-weighted images were compared with histologic findings in 3 autopsy-proved cases of ALSD. RESULTS: Antemortem MR images showed atrophy of the frontal and temporal lobes, which were asymmetric in the medial-ventral part of the temporal lobe. Faint linear T2-hyperintensity was seen in the medial-ventral part of the temporal subcortical white matter in 1 case. Postmortem T2-weighted images showed linear subcortical hyperintensity in the ventral-medial temporal lobe in each case. Histologically, cortical atrophy on MR images showed spongiform change with neuronal loss and gliosis especially in the superficial layers and linear subcortical hyperintensity on T2-weighted images showed degeneration and gliosis in each case. These findings are characteristic histologic changes of ALSD. CONCLUSION: MR imaging of atrophy of the frontal and temporal lobes with linear subcortical hyperintensities in the anteromedial temporal lobe is useful for diagnosis of ALSD.     

Detection of corticospinal tract compromise in amyotrophic lateral sclerosis with brain MR imaging: relevance of the T1-weighted spin-echo magnetization transfer contrast sequence

BACKGROUND AND PURPOSE: Hyperintensity in the posterior limb of the internal capsule at T2-weighted MR imaging, consistent with corticospinal tract (CST) degeneration, is described in amyotrophic lateral sclerosis (ALS). However, the lack of specific tests or biological markers hinders confirmation of the diagnosis, especially in the early stages. We investigated the CST in ALS with MR imaging. METHODS: We examined 25 patients (14 men, 11 women; mean age, 49.1 years; range, 29-68 years) and 21 age- and sex-matched control subjects without upper motor neuron signs. According to the revised El Escorial criteria, 22 patients had definite ALS; two, probable ALS; and one, suspected ALS. Fluid-attenuated inversion recovery (FLAIR; TR/TE/TI, 11,000/140/2600) and T1-weighted spin-echo (SE)/magnetization transfer contrast-enhanced (MTC; TR/TE, 510/12) imaging was performed at 1 T. Two experienced neuroradiologists blinded to the patients' history independently evaluated the CST. RESULTS: T1-weighted SE MTC imaging allowed visualization of the CST in both patients and control subjects. T1-weighted SE MTC images showed hypointensity along the CST and bilateral subcortical regions of the precentral gyri in all control subjects and hyperintensity in 80% of patients with ALS (P < .05). FLAIR images showed hyperintensity in these areas in both groups, with no significant difference. CONCLUSION: T1-weighted SE MTC imaging is sensitive and accurate in depicting CST lesions in ALS, whereas FLAIR imaging is not. T1-weighted SE MTC imaging is useful in diagnosing ALS by showing hyperintense areas along the CST, which separates patients from control subjects. This sequence should be included in the workup of patients with weakness and pyramidal signs.     

肌萎缩侧索硬化症MRI研究进展

肌萎缩侧索硬化(ALS)是一种以上、下运动神经元受累为主要特征的慢性进行性神经系统变性性疾病。下运动神经元功能障碍可经肌电图和肌肉活检证实,而上运动神经元受累尤其在早期难以检测。常规MRI和功能MRI技术如扩散张量成像（DTI）、磁共振波谱（MRS）和静息态功能MRI（rs-fMRI）等,可以检测ALS 运动区及非运动区变化,对疾病的早期诊断和监测有一定作用。就MRI技术及其在ALS中的应用进行综述。     

Whole-brain and regional brain atrophy in amyotrophic lateral sclerosis

BACKGROUND AND PURPOSE: Recent evidence from neuropsychologic and neuroimaging studies suggests that central nervous system involvement in amyotrophic lateral sclerosis (ALS) extends beyond motor neurons. Our purpose was to obtain measures of global and regional atrophy in nondemented patients with ALS to assess subtle structural brain changes. METHODS: MR images, acquired from 16 patients and 9 healthy subjects (HS), were processed by using the Structural Imaging Evaluation of Normalized Atrophy (SIENA) software to estimate whole-brain atrophy measures and the voxel-based morphometry (VBM) method to highlight the selective volumetric decrease of single cerebral areas. In addition, each subject underwent a neuropsychologic examination. RESULTS: In patients with ALS, brain parenchymal fraction was slightly lower compared with HS (P = .012), and seemed to be related to the presence of cognitive impairment. Patients showed a gray matter volume decrease in several frontal and temporal areas bilaterally (P < .001 uncorrected) compared with HS, with a slight prevalence in the right hemisphere. No volume reduction in primary motor cortices of patients was detected. Performances on Symbol Digit Modalities Test were significantly worse in patients compared with HS (P = .025). CONCLUSIONS: The presence of mild whole-brain volume loss and regional frontotemporal atrophy in patients with ALS could explain the presence of cognitive impairment and confirms the idea of ALS as a degenerative brain disease not confined to motor system.