Hippocampal atrophy in temporal lobe epilepsy: the 'generator' and 'receiver'.

OBJECTIVE: Some patients with unilateral medial temporal lobe epilepsy (MTLE) display bilateral hippocampal atrophy on MRI, even though seizures originate in only one hippocampus. The correct identification of the epileptogenic hippocampus (the 'generator') vs the non-epileptogenic (the 'receiver') may lead to better surgical planning and results. MATERIALS AND METHODS: We studied 14 patients with MTLE (eight left and six right) who became seizure free after unilateral hippocampal resection, with hippocampal sclerosis confirmed by histology. Hippocampal tridimensional morphometry was performed comparing patients and healthy controls employing a voxel-wise Wilcoxon test. Results were corrected for multiple comparisons with the application of a False Discovery Rate (FDR)-corrected threshold for q < 0.05. RESULTS: Patients with MTLE showed atrophy involving the ipsilateral hippocampus and the contralateral hippocampus, more pronouncedly within the ipsilateral hippocampus in the anterior-inferior aspect of the hippocampal head (left MTLE, left hippocampus x = -28, y = -16, z = -24, Z = 3.6; right MTLE, right hippocampus x = 22, y = -11, z = -27, Z = 2.9). On the contralateral hippocampus, the atrophy was more noticeable in the posterior head and body areas. CONCLUSION: The epileptogenic hippocampal atrophy has an anatomically distinct pattern compared with the contralateral hippocampus. This information may help guide the presurgical assessment of MTLE.

Disconnection as a mechanism for cognitive dysfunction in multiple sclerosis.

Disconnection of cognitively important processing regions by injury to the interconnecting white matter provides a potential mechanism for cognitive dysfunction in multiple sclerosis. The contribution of tract-specific white matter injury to dysfunction in different cognitive domains in patients with multiple sclerosis has not previously been studied. We apply tract-based spatial statistics (TBSS) to diffusion tensor imaging (DTI) in a cohort of multiple sclerosis patients to identify loci where reduced white matter tract fractional anisotropy (FA) predicts impaired performance in cognitive testing. Thirty-seven multiple sclerosis patients in remission (median age 43.5 years; Expanded Disability Status Scale range 1.5-6.5; 35 relapsing remitting, two secondary-progressive) underwent 3 T MRI including high-resolution DTI. Multiple sclerosis patients underwent formal testing of performance in multiple cognitive domains. Normalized cognitive scores were used for voxel-wise statistical analysis using TBSS, while treating age as a covariate of no interest. Permutation-based inference on cluster size (t > 2, P <0.05 corrected) was used to correct for multiple comparisons. Statistical mapping revealed differential patterns of FA reduction for tests of sustained attention, working memory and processing speed, visual working memory and verbal learning and recall. FA was not associated with frontal lobe function or visuospatial perception. Cognitively relevant tract localizations only partially overlapped with areas of high FLAIR lesion probability, confirming the contribution of normal-appearing white matter abnormality to cognitive dysfunction. Of note, tract localizations showing significant associations with cognitive impairment were found to interconnect cortical regions thought to be involved in processing in these cognitive domains, or involve possible compensatory processing pathways. This suggests that TBSS reveals functionally relevant tract injury underlying cognitive dysfunction in patients with multiple sclerosis.

Development of an inventory of biomedical imaging physics learning outcomes for MRI radiographers.

INTRODUCTION: MRI is highly physics based yet no research-based inventory of physics learning outcomes specific to MRI radiographers was found in the literature. The purpose of this study was the development of such an inventory using a multi-stakeholder, multi-disciplinary approach (as advised by the WHO) and which would support a previously published competence profile. METHODS: The inventory was developed in two phases: Phase 1: Development of an initial version of the learning outcomes inventory required to be able to deliver the competences via an analysis of textbooks and literature and validated by a small (n = 3) expert advisory group Phase 2: Final validation carried out via a bigger (n = 15) international group of subject matter experts (SMEs). Consensus was achieved via a dichotomous web-based questionnaire. RESULTS: At 70% level of consensus the expert group validated an inventory of biomedical physics learning outcomes consisting of 281 knowledge and skill statements. It is subdivided into two sections: 'fundamental' physics learning outcomes which are generic to all competences and 'additional' physics learning outcomes specific to each individual competence. CONCLUSION: The process used is sufficiently generic to be easily adapted to the development of physics learning outcome inventories in other specialties of radiography and for other healthcare professions whose work involves highly technological medical devices. As a result of this study, the current MRI curriculum would need to be revised as it was not based on a formal systematic research process and many learning outcomes are in fact missing.

Evaluation of the Implementation of the Response Assessment in Neuro-Oncology Criteria in the HERBY Trial of Pediatric Patients with Newly Diagnosed High-Grade Gliomas.

BACKGROUND AND PURPOSE: HERBY was a Phase II multicenter trial setup to establish the efficacy and safety of adding bevacizumab to radiation therapy and temozolomide in pediatric patients with newly diagnosed non-brain stem high-grade gliomas. This study evaluates the implementation of the radiologic aspects of HERBY. MATERIALS AND METHODS: We analyzed multimodal imaging compliance rates and scan quality for participating sites, adjudication rates and reading times for the central review process, the influence of different Response Assessment in Neuro-Oncology criteria in the final response, the incidence of pseudoprogression, and the benefit of incorporating multimodal imaging into the decision process. RESULTS: Multimodal imaging compliance rates were the following: diffusion, 82%; perfusion, 60%; and spectroscopy, 48%. Neuroradiologists' responses differed for 50% of scans, requiring adjudication, with a total average reading time per patient of approximately 3 hours. Pseudoprogression occurred in 10/116 (9%) cases, 8 in the radiation therapy/temozolomide arm and 2 in the bevacizumab arm (P < .01). Increased target enhancing lesion diameter was a reason for progression in 8/86 cases (9.3%) but never the only radiologic or clinical reason. Event-free survival was predicted earlier in 5/86 (5.8%) patients by multimodal imaging (diffusion, n = 4; perfusion, n = 1). CONCLUSIONS: The addition of multimodal imaging to the response criteria modified the assessment in a small number of cases, determining progression earlier than structural imaging alone. Increased target lesion diameter, accounting for a large proportion of reading time, was never the only reason to designate disease progression.

Use of combined conventional and quantitative MRI to quantify pathology related to cognitive impairment in multiple sclerosis.

BACKGROUND: Cognitive impairment is one of the frequent and early findings in multiple sclerosis (MS). OBJECTIVE: To determine the relation between cognitive abnormalities and the extent of macroscopic and microscopic tissue damage in the corpus callosum (CC), revealed by conventional magnetic resonance imaging (MRI), magnetisation transfer imaging (MTI) and diffusion tensor imaging (DTI). METHODS: Conventional dual-echo, DTI and MTI of the brain were obtained from 36 patients with relapsing remitting (RR) MS, and 13 age and gender matched normal controls. Voxels from CC were identified using a tractography based algorithm. Mean apparent diffusion coefficient (ADC(av)) and MT ratio were measured for the CC as defined by tractography. Corpus callosum area (CCA) was measured using edge detection on the mid-sagittal slice on high resolution MRI images. The Expanded Disability Status Scale (EDSS) and Paced Auditory Serial Addition Test (PASAT) were scored. RESULTS: Nine patients (25%) were found to be cognitively impaired. The CCA was not significantly different in the whole cohort of patients from controls (608.2 (428.6-713.0) mm(2) vs 674.2 (585.8-754.4) mm(2), p = 0.1), but was smaller in cognitively impaired than unimpaired group (417 (290-634) mm(2) vs 652 (511-718) mm(2), p = 0.04). The mean MT ratio of CC in patients was lower than in controls (0.41 (0.39-0.042) vs 0.43 (0.42-0.43), p<0.001). The ADC(av) in the CC in patients was higher than in controls (0.94 (0.89-0.99) vs 0.87 (0.85-0.89), p<0.001). PASAT was correlated with mean MT ratio (r = 0.47, p = 0.0046), ADC(av) (r = -0.53, p = 0.0012), CCA (r = 0.42, p = 0.01) and total T(2) lesion load (r = -0.4, p = 0.017), but not with T(2) lesion load within the CC (r = -0.24, p = 0.16), disease duration (r = -0.2, p = 0.24) or EDSS (r = -0.27, p = 0.12). CONCLUSIONS: ADC(av), MTR and atrophy measures in the CC may offer a sensitive method detecting subtle macroscopic and microscopic changes associated with cognitive impairment in MS.

An international survey of MRI qualification and certification frameworks with an emphasis on identifying elements of good practice.

The purpose of the study was to survey MRI qualification and certification frameworks in the major English-speaking countries (Australia, New Zealand, US, Canada, UK, Ireland) with the aim of identifying elements of good practice. The intention is to incorporate these elements in a national framework that could be used in supporting an MRI specialist register. The study was conducted using document analysis of MRI qualification and certification documents from these states with data triangulated through a web-based questionnaire amongst an expert group of MRI radiographers (n = 59) from the same states. Based on the results of the study, recommendations have been put forward for those countries that are in the process of developing such frameworks. The main recommendations include that a professional or regulatory body externally accredits MRI programmes and that learning outcomes be based on an MRI competence profile that addresses current and forecasted needs of the particular country. The MRI competence profile should encompass a novice-to expert continuum and be referenced directly to a national qualification framework. Ideally each level of expertise should be assessed and evidenced by a portfolio of CPD activities, including clinical and management case studies appropriate to that level.

Deep gray matter and fatigue in MS: a T1 relaxation time study.

UNLABELLED: Fatigue in multiple sclerosis (MS) occurs commonly, sometimes as the earliest symptom. Some MS patients consider fatigue to be their most troublesome complaint, and it has been shown to be an independent predictor of impaired quality of life. Several reports have demonstrated that subcortical gray matter pathology is related to fatigue. We hypothesized that MRI detectable changes in the deep gray matter of MS patients may correlate with fatigue severity. Our objective was: to assess the relationship between fatigue severity and detectable changes on magnetic resonance imaging (MRI), quantified using the mean T1 relaxation time (T1), in deep gray matter structures in relapsing remitting multiple sclerosis (RRMS). Using region of interest analysis, T1 values were measured for the thalamus, putamen and caudate nucleus in 52 RRMS patients and 19 healthy volunteers. Fatigue was assessed using the Fatigue Severity Scale. RESULTS: The median T1 in the thalamus and the putamen were significantly higher in the patient cohort than in the healthy controls; the median T1 in the caudate was also higher in the MS patients but did not reach statistical significance. There was a significant correlation between fatigue severity and the T1 of the thalamus (rho = 0.418; p = 0.014). Furthermore, the median T1 in the thalamus was significantly higher in patients with fatigue compared with those without (p = 0.018). Our results provide further evidence for the role of subcortical gray matter structures in the pathogenesis of multiple sclerosis (MS)-related fatigue. This study also demonstrates that T1 relaxation time measurement is a suitable technique for detecting abnormalities of the deep gray matter in RRMS and presents further support of gray matter involvement in MS.

Response Assessment in Pediatric Neuro-Oncology: Implementation and Expansion of the RANO Criteria in a Randomized Phase II Trial of Pediatric Patients with Newly Diagnosed High-Grade Gliomas.

Determination of tumor response to treatment in neuro-oncology is challenging, particularly when antiangiogenic agents are considered. Nontumoral factors (eg, blood-brain barrier disruption, edema, and necrosis) can alter contrast enhancement independent of true tumor response/progression. Furthermore, gliomas are often infiltrative, with nonenhancing components. In adults, the Response Assessment in Neuro-Oncology (RANO) criteria attempted to address these issues. No such guidelines exist yet for children. The ongoing randomized phase II trial, A Study of Avastin (bevacizumab) in Combination With Temolozomide (TMZ) and Radiotherapy in Paediatric and Adolescent Patients With High-Grade Glioma (HERBY), will establish the efficacy and safety of the antiangiogenic agent bevacizumab for the first-line treatment of newly diagnosed high-grade glioma in children (n = 121 patients, enrollment complete). The primary end point is event-free survival (tumor progression/recurrence by central review, second primary malignancy, or death). Determination of progression or response is based on predefined clinical and radiographic criteria, modeled on the RANO criteria and supported by expert pseudoprogression review and the use of standardized imaging protocols. The HERBY trial will also compare conventional MR imaging (T1-weighted and T2/fluid-attenuated inversion recovery sequences) with conventional MR imaging plus diffusion/perfusion imaging for response assessment. It is anticipated that HERBY will provide new insights into antiangiogenic-treated pediatric brain tumors. HERBY will also investigate the practicality of obtaining adequate quality diffusion/perfusion scans in a trial setting, and the feasibility of implementing standard imaging protocols across multiple sites. To date, 61/73 (83.6%) patients with available data have completed diffusion-weighted imaging (uptake of other nonconventional techniques has been limited). Harmonization of imaging protocols and techniques may improve the robustness of pediatric neuro-oncology studies and aid future trial comparability.

Proton magnetic resonance spectroscopy and outcome in term neonates with chorioamnionitis.

OBJECTIVE: Evaluate brain metabolites, which reflect neuroinflammation, and relate to neurodevelopmental outcomes in healthy term neonates exposed to chorioamnionitis. STUDY DESIGN: Thirty-one healthy term neonates with documented fetal inflammatory response after maternal chorioamnionitis underwent magnetic resonance spectroscopy (MRS), with voxels placed in basal ganglia (BG) and frontal white matter. Bayley III examinations were performed at 12 months of age. RESULT: Infants with below average outcomes did not show the same increase in NAA/Cho ratios postnatally as the group with normal outcomes. Decreased NAA/Cho and increased Lac/Cr in BG correlated with lower motor and cognitive composite scores, respectively, controlling for postnatal age. In males, increased lactate/NAA in BG were associated with lower motor scores. Funisitis severity was associated with decreased NAA/Cho and increased mI/NAA in males. CONCLUSION: In healthy term newborns with chorioamnionitis, MRS ratios shortly after birth may provide evidence of occult neuroinflammation, which may be associated with worse performance on 1-year neurodevelopmental tests.

Perfusion MRI of infarcted and noninfarcted brain tissue in stroke: a comparison of conventional hemodynamic imaging and factor analysis of dynamic studies.

RATIONALE AND OBJECTIVES: To investigate the hemodynamics of infarcted and noninfarcted regions of the brain in patients with stroke secondary to a complete middle cerebral artery occlusion. Also, to compare factor analysis, a novel method of analyzing perfusion-weighted images, with more conventional techniques. METHODS: Twenty-two patients with complete unilateral occlusion of the middle cerebral artery were examined by T1-weighted, contrast-enhanced, perfusion-weighted imaging, diffusion-weighted imaging, and magnetic resonance angiography. Quantitative cerebral blood volume (CBV), cerebral blood flow (CBF), and time-to-peak-intensity (TTP) images were generated. Factor analysis of dynamic studies (FADS) was used to generate "early" and "late" images. The hemodynamic parameters for the infarcted and noninfarcted regions of the occluded territory were compared with those for the brain territory on the nonoccluded side. RESULTS: Three regions were shown: (1) Normal tissue on the unaffected side; (2) an infarcted region, which was characterized by reduced CBV, CBF, and early FADS values with increased TTP values; and (3) a noninfarcted region with reduced early FADS and increased late FADS and TTP values compared with the normal region. Cerebral blood volume and CBF values were not reduced significantly in the noninfarcted region. CONCLUSIONS: The differences in parameters such as TTP, CBV, and CBF are significant, and it is necessary to use more than one parameter when interpreting magnetic resonance imaging perfusion data. Factor analysis of dynamic studies provides additional information to conventional methods of analyzing perfusion data.

Extracting parametric images from dynamic contrast-enhanced MRI studies of the brain using factor analysis.

Factor analysis of dynamic studies (FADS) is a technique that allows structures with different temporal characteristics to be extracted from dynamic contrast enhanced studies without making any a priori assumptions about physiology. These dynamic structures may correspond to different tissue types or different organs or they may simply be a useful way of characterising the data. This paper describes a method of automatically extracting factor images and curves from contrast enhanced MRI studies of the brain. This method has been applied to 107 studies carried out on patients with acute stroke. The results show that FADS is able to extract factor curves correlated to arterial and venous signal intensity curves and that the corresponding factor images allow a distinction to be made between areas of the brain with normal and abnormal perfusion. The method is robust and can be applied routinely to dynamic studies of the brain. The constraints described are sufficiently general to be applicable to other dynamic MRI contrast enhanced studies where an increase in contrast concentration produces an increase in signal intensity.

Ultra-high-field imaging distinguishes MS lesions from asymptomatic white matter lesions.

OBJECTIVES: To investigate whether multiple sclerosis (MS) and non-MS white matter brain lesions can be distinguished by their appearance on 7 T T2*-weighted MRI. METHODS: This was an observational study of 28 patients with MS and 17 patients with cerebral white matter lesions who did not have MS. Subjects were imaged using 7 T T2*-weighted imaging. White matter lesions were identified and analyzed for volume, location, and perivenous appearance. RESULTS: Out of 901 lesions identified in patients with MS, 80% were perivenous. In comparison, 19% of 428 lesions identified in patients without MS had a perivenous appearance. Seven-Tesla T2*-weighted MRI reliably distinguished all patients with clinically definite MS (>40% lesions appeared perivenous) from those without clinical MS (<40% lesions appeared perivenous). Perivenous lesion appearance was more predictive of MS (odds ratio [OR] 14, p < 0.001) than subcortical or periventricular lesion location (OR 4.5, p < 0.001, and OR 2.4, p = 0.009). Perivenous lesion appearance was observed with a similar frequency in patients with clinically isolated syndrome of demyelination and in early (gadolinium-enhancing) MS lesions. CONCLUSION: Perivenous lesion location on 7 T T2*-weighted imaging is predictive of the presence of demyelination. Optimization of this imaging technique at lower magnetic resonance field strengths would offer benefit for the diagnosis of MS.

Cerebral white matter hyperintense lesions are associated with unstable carotid plaques.

OBJECTIVES: The aim of this study was to determine whether unstable carotid plaques, a known risk factor for cerebral emboli, are associated with cerebral white matter lesions. METHODS: Seventy-one symptomatic patients undergoing magnetic resonance imaging prior to carotid endarterectomy for high grade carotid stenosis were included in this study. The number and volume of white matter hyperintense lesions (WMHL) on fluid attenuated inversion recovery brain scans were compared according to the morphology of carotid plaque based upon the American Heart Association (AHA) histological classification. RESULTS: Of the 57 patients who had good quality brain scans and non-fragmented carotid plaques, 15 plaques were defined as stable (type V) and 42 as unstable (type VI). After adjustment for the major risk factors affecting WMHL, unstable carotid plaques were found to be associated with more WMHL in the ipsilateral cerebral hemisphere than stable plaques (transformed means 2.50+/-1.2 vs. 1.53+/-1.1, p=0.016), however, there was only a trend towards larger WMHL volumes (p=0.079). CONCLUSIONS: The observed association between unstable carotid plaques and the number of white matter lesions suggest that thromboembolic plaque activity may contribute to the development of leukoaraiosis, in particular smaller individual lesions. Larger studies are warranted to confirm this finding and explore the potential clinical impact for selecting candidates for carotid endarterectomy.

Collection and local use of accident and emergency hospital data in England.

OBJECTIVE: To obtain information on the collection and local use of accident and emergency data. METHODS: A postal questionnaire was sent to 248 English accident and emergency (A&E) departments. Responses were obtained from 217 (88%). RESULTS: Only 87 (40%) of departments were fully computerised, with 109 (50%) using manual systems, and 21 (10%) a mixture of both. Significantly more computerised departments reported that they undertook studies (epidemiological, accident prevention, and resource management) than non-computerised departments. Only limited information on the types of injury studied was provided. The most common topics were childhood accidents, road traffic accidents, and poisonings. Staff in 45 departments (21%) reported membership of safety organisations. Around 90% of departments reported that they notified general practitioners and health visitors of their patients' attendance, usually within 3 d of the event. CONCLUSIONS: Computerisation appears to help the collection of A&E data for public health research. There is scope to increase the involvement of public health and other workers in epidemiological studies using A&E data. A&E departments should themselves become more involved with local safety organisations.

General practitioners' attitudes to child injury prevention in the UK: a national postal questionnaire.

OBJECTIVE: To survey the level of interest and involvement in child injury prevention among general practitioners and their practice teams, and to identify factors associated with current interest. DESIGN: Postal survey of a random sample of United Kingdom (UK) medical practitioners. SETTING: Medical practices throughout the UK. SUBJECTS: 957 general practitioners (50% of the total sample) who responded to the survey questionnaire. OUTCOMES: Answer to questions about role in injury prevention. RESULTS: Despite a response rate of only 50%, this study is the largest to examine the role of general practitioners in child injury prevention. Seven hundred and twenty five (77%) of the respondents considered injury prevention to be part of the general practitioner's role, but only 260 (28%) felt that they did enough in this area. Time was cited as the most significant limiting factor. Women doctors, rural practitioners, members of the Royal College of General Practitioners, and doctors with previous personal experience of serious accidents all had more positive attitudes to injury prevention as a routine part of their activities (p < 0.05). Practices providing first aid training for staff were also associated with an interest in injury prevention. The most appropriate times for offering prevention advice were thought to be during child health surveillance clinics and during treatment of an accident. CONCLUSIONS: Awareness about injury prevention opportunities might be improved by emphasising the roles of individual team members and by better addressing the training needs of the whole team.

Quantitative diffusion characteristics of the human brain depend on MRI sequence parameters.

Quantitative diffusion-weighted MRI has been applied to the study of neurological diseases, including multiple sclerosis, where the molecular self-diffusion coefficient D has been measured in both lesions and normal-appearing white matter. Histograms of D have been used as a novel measure of the "lesion load", with potential applications that include the monitoring of efficacy in new treatment trials. However different ways of measuring D may affect its value, making comparison between different centres and research groups impossible. We aimed to assess the effect, if any, of using two different MRI sequences on the value of D. We studied 13 healthy volunteers, using two different quantitative diffusion sequences (including different b(max) values and gradient applications). Maps of D were analysed using both regions of interest (ROI) in white matter and "whole brain" histograms, and compared between the two sequences. In addition, we studied three standardised test liquids (with known values of D) using both sequences. Histograms from the two sequences had different distributions, with a greater spread and higher peak position from the sequence with lower b(max). This greater spread of D was also evident in the white matter and test liquid ROI. "Limits of agreement" analysis demonstrated that the differences could be clinically relevant, despite significant correlations between the sequences obtained using simple rank methods. We conclude that different quantitative diffusion sequences are unlikely to produce directly comparable values of D, particularly if different b(max) values are used. In addition, the use of inappropriate statistical tests may give false impressions of close agreement. Standardisation of methods for the measurement of D are required if these techniques are to become useful tools, for example in monitoring changes in the disease burden of multiple sclerosis.

Improved white matter fiber tracking using stochastic labeling.

Diffusion tensor imaging (DTI) promises a robust means of visualizing in vivo white matter fibers in individual subjects, and of inferring direct connectivity between distant points in the brain. By following the primary eigenvector of the diffusion tensor, trajectories may be defined that trace the path of the underlying fiber tract. However, fiber tracking is prone to cumulative error from acquisition noise and partial volume, which limits the repeatability of such techniques. An image-processing method based on stochastic labeling, by which the noisy primary eigenvectors may be reconfigured according to anatomically reasonable assumptions, is described. The method's potential to improve fiber tracking is first demonstrated on numerical test data. It is then applied to real data acquired from healthy volunteers. Trajectories defined within the corpus callosum and the pyramidal tracts are rendered using 3D graphic imaging software, and the results are compared before and after processing. Fiber tracking was shown to produce anatomically plausible results, and typical errors were largely resolved by the method. Further, the sensitivity of trajectories to their start point was greatly reduced after processing. The use of stochastic labeling may therefore improve the reliability of experiments using white matter fiber tracking.

White matter mapping using diffusion tensor MRI.

Diffusion tensor MRI is used to define trajectories that reflect the long-range order of in vivo white matter (WM) fiber tracts. Fiber tracking is particularly prone to cumulative error from noise and partial volume along the length of the trajectory paths, but the overall shape of each path is anatomically meaningful. By considering only the long-range similarity of path shapes, a method of constructing 3D maps of specific WM structures has been developed. A trajectory is first computed from an operator-selected seed voxel, located within the anatomical structure of interest (SOI). Voxels from the same structure are then automatically identified based on the similarity of trajectory path shapes, assessed using Pearson's correlation coefficient. The corpus callosum and pyramidal tracts in 14 patients with multiple sclerosis, and in 10 healthy controls were mapped by this method, and the apparent diffusion coefficient (ADC) was measured. The ADC was significantly higher in patients than in controls, and higher in the corpus callosum than in the pyramidal tracts for both groups. Using this method the different functional structures in the WM may be identified and mapped. Within these maps, MRI parameters can be measured for subsequent comparison with relevant clinical data.

Quantitative diffusion weighted magnetic resonance imaging, cerebral atrophy, and disability in multiple sclerosis.

OBJECTIVES: To investigate the relations between quantitative diffusion coefficient MRI histograms, clinical variables, and cerebral atrophy. METHODS: Twenty two patients with clinically definite multiple sclerosis and 11 healthy volunteers were studied. Histograms of apparent diffusion coefficient (ADC) from a volume of interest that included multiple slices encompassing the lateral ventricles were processed from diffusion weighted MRI. In addition, total lesion load was measured on T2 weighted dual echo images, and cerebral volume from 3D magnetisation prepared rapid acquisition gradient echo scans. All patients underwent neurological assessment, including disability on the expanded disability status scale (EDSS). RESULTS: Histograms from the patient group showed a reduced peak height and a "right shift" compared with healthy controls. Peak height of the diffusion histogram correlated with both EDSS (r=-0.54, p=0.0101) and disease duration (r=-0.52, p=0.0140), but not with age. Brain volume correlated with peak height of the ADC histogram (r=0.55, p=0.0129), but not with disability. Total lesion load also correlated moderately with EDSS (r=0.46, p=0.03). CONCLUSIONS: This study shows for the first time that quantitative MRI measures of diffusion correlate with clinical variables (disability, disease duration) and cerebral atrophy in multiple sclerosis. Cerebral atrophy and fixed neurological deficit may be attributed to axonal loss, which would be expected to have a significant effect on ADC. Extension of this method to more patients and longitudinal studies will further elucidate its sensitivity, reproducibility, and potential role in clinical practice and treatment trials.

Pyramidal tract mapping by diffusion tensor magnetic resonance imaging in multiple sclerosis: improving correlations with disability.

BACKGROUND: Current magnetic resonance imaging (MRI) outcome measures such as T2 lesion load correlate poorly with disability in multiple sclerosis. Diffusion tensor imaging (DTI) of the brain can provide unique information regarding the orientation and integrity of white matter tracts in vivo. OBJECTIVE: To use this information to map the pyramidal tracts of patients with multiple sclerosis, investigate the relation between burden of disease in the tracts and disability, and compare this with more global magnetic resonance estimates of disease burden. METHODS: 25 patients with relapsing-remitting multiple sclerosis and 17 healthy volunteers were studied with DTI. An algorithm was used that automatically produced anatomically plausible maps of white matter tracts. The integrity of the pyramidal tracts was assessed using relative anisotropy and a novel measure (L(t)) derived from the compounded relative anisotropy along the tracts. The methods were compared with both traditional and more recent techniques for measuring disease burden in multiple sclerosis (T2 lesion load and "whole brain" diffusion histograms). RESULTS: Relative anisotropy and L(t) were significantly lower in patients than controls (p < 0.05). Pyramidal tract L(t) in the patients correlated significantly with both expanded disability status scale (r = -0.48, p < 0.05), and to a greater degree, the pyramidal Kurtzke functional system score (KFS-p) (r = -0.75, p < 0.0001). T2 lesion load and diffusion histogram parameters did not correlate with disability. CONCLUSIONS: Tract mapping using DTI is feasible and may increase the specificity of MRI in multiple sclerosis by matching appropriate tracts with specific clinical scoring systems. These techniques may be applicable to a wide range of neurological conditions.