Diagnostic Accuracy of Diffusion Tensor Imaging in Amyotrophic Lateral Sclerosis: A Systematic Review and Individual Patient Data Meta-Analysis

doi:10.1016/j.acra.2013.03.017

Academic Radiology

Volume 20, Issue 9, September 2013, Pages 1099-1106

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https://doi.org/10.1016/j.acra.2013.03.017 Get rights and content

Rationale and Objectives

There have been a large number of case-control studies using diffusion tensor imaging (DTI) in amyotrophic lateral sclerosis (ALS). The objective of this study was to perform an individual patient data (IPD) meta-analysis for the estimation of the diagnostic accuracy measures of DTI in the diagnosis of ALS using corticospinal tract data.

Materials and Methods

MEDLINE, EMBASE, CINAHL, and Cochrane databases (1966–April 2011) were searched. Studies were included if they used DTI region of interest or tractography techniques to compare mean cerebral corticospinal tract fractional anisotropy values between ALS subjects and healthy controls. Corresponding authors from the identified articles were contacted to collect individual patient data. IPD meta-analysis and meta-regression were performed using Stata. Meta-regression covariate analysis included age, gender, disease duration, and Revised Amyotrophic Lateral Sclerosis Functional Rating Scale scores.

Results

Of 30 identified studies, 11 corresponding authors provided IPD and 221 ALS patients and 187 healthy control subjects were available for study. Pooled area under the receiver operating characteristic curve (AUC) was 0.75 (95% CI: 0.66–0.83), pooled sensitivity was 0.68 (95% CI: 0.62–0.75), and pooled specificity was 0.73 (95% CI: 0.66–0.80). Meta-regression showed no significant differences in pooled AUC for each of the covariates. There was moderate to high heterogeneity of pooled AUC estimates. Study quality was generally high. Data from 19 of the 30 eligible studies were not ascertained, raising possibility of selection bias.

Conclusion

Using corticospinal tract individual patient data, the diagnostic accuracy of DTI appears to lack sufficient discrimination in isolation. Additional research efforts and a multimodal approach that also includes ALS mimics will be required to make neuroimaging a critical component in the workup of ALS.

Section snippets

Eligibility Criteria

We conducted MEDLINE (1966–April 2011), EMBASE (1999–April 2011), CINAHL (1999–April 2011), and Cochrane (2005–April 2011) searches. Search keywords included: amyotrophic lateral sclerosis, Lou Gehrig's, magnetic resonance imaging, diagnostic imaging, diagnostic tests, diffusion tensor imaging, or fractional anisotropy. Full electronic search for MEDLINE is presented in Appendix Table 1. There were no language restrictions. A manual search of reference lists from identified articles was

Study Selection

We provide the number of studies screened, assessed for eligibility, and included for review with reasons for exclusions at each stage in Figure 1. We collected individual patient data from 11 of 30 identified studies.

Study Characteristics

Study characteristics of the studies are summarized in Table 1 with additional study details in Appendix Table 2 7, 8, 13, 19, 23, 24, 25, 26, 27, 28, 29. Studies enrolled 221 ALS subjects and 187 HCs. Equipment, DTI parameters, and analysis methods varied across studies. All

Discussion

Conventional MRI findings in ALS are neither sensitive nor specific (30). Therefore, there has been great interest in using advanced neuroimaging methods such as DTI as diagnostic ALS biomarkers. Quantitative meta-analysis is necessary to properly evaluate the potential of new technologies to serve as diagnostic tests, particularly in the setting of imaging studies, which include relatively small numbers of subjects. Based on the available IPD, the meta-analysis results suggest that the mean FA

Acknowledgments

M.B. thanks Dr. John D. Carew and Dr. Govind Nair for their contributions to the article. C.E. thanks Prof. P.N. Leigh and Dr. Andy Simmons for their contributions to the article. B.R.F. thanks the Johns Hopkins Graduate Training Programs in Clinical Investigation for its mentorship. The Ciccarelli et al study was performed using a 1.5 T scanner funded by the MS Society of Great Britain and Northern Ireland and by the Department of Health National Institute of Health Research Biomedical Research

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Radiology Alliance for Health Services ResearchDiagnostic Accuracy of Diffusion Tensor Imaging in Amyotrophic Lateral Sclerosis: A Systematic Review and Individual Patient Data Meta-Analysis

Rationale and Objectives

Materials and Methods

Results

Conclusion

Section snippets

Eligibility Criteria

Study Selection

Study Characteristics

Discussion

Acknowledgments

J Neurol Sci

Clin Neurol Neurosurg

NeuroRx

Lancet Neurol

Lancet Neurol

Acad Radiol

J Clin Epidemiol

Neuromuscul Disord

Brain Res

Amyotrophic lateral sclerosis: objective upper motor neuron markers

Curr Neurol Neurosci Rep

Evaluation of corticospinal tract impairment in the brain of patients with amyotrophic lateral sclerosis by using diffusion tensor imaging acquisition schemes with different numbers of diffusion-weighting directions

J Comput Assist Tomogr

Corpus callosum involvement is a consistent feature of amyotrophic lateral sclerosis

Neurology

Differential corticospinal tract degeneration in homozygous 'D90A'SOD-1 ALS and sporadic ALS

J Neurol Neurosurg Psychiatry

Diffusion tensor imaging for the assessment of upper motor neuron integrity in ALS

Neurology

Diffusion tensor MRI and MR spectroscopy in long lasting upper motor neuron involvement in amyotrophic lateral sclerosis

Arch Ital Biol

Combined 3T diffusion tensor tractography and H-1-MR spectroscopy in motor neuron disease

Am J Neuroradiol

Combined structural and neurochemical evaluation of the corticospinal tract in amyotrophic lateral sclerosis

Amyotroph Lateral Scler

Radiology Alliance for Health Services Research
Diagnostic Accuracy of Diffusion Tensor Imaging in Amyotrophic Lateral Sclerosis: A Systematic Review and Individual Patient Data Meta-Analysis