Translating State-Of-The-Art Spinal Cord MRI Techniques To Clinical Use: A Systematic Review Of Clinical Studies Utilizing DTI, MT, MWF, MRS, and fMRI
Allan R. Martin1, Izabela Aleksanderek1, Julien Cohen-Adad2, Zenovia Tarmohamed3, Lindsay Tetreault1, Nathaniel Smith4, David W. Cadotte1, Adrian Crawley5, Howard Ginsberg1, David J. Mikulis5, and Michael G. Fehlings1

1Neurosurgery, University of Toronto, Toronto, ON, Canada, 2Electrical Engineering, Polytechnique Montreal, Montreal, QC, Canada, 3Royal College of Surgeons Ireland, Dublin, Ireland, 4McMaster University, Hamilton, ON, Canada, 5Medical Imaging, University of Toronto, Toronto, ON, Canada

Synopsis

5 state-of-the-art spinal cord MRI techniques have been identified with great clinical potential. This systematic review finds trends in the technical methods employed and measures the progress of these techniques toward clinical translation. 104 studies were identified, with 69 DTI, 25 MT, 1 MWF, 11 MRS, and 8 fMRI studies. The DTI metric FA has the strongest evidence of utility, correlating with disability in numerous spinal conditions. Large, well-designed studies with a priori hypotheses, standardized acquisition methods, detailed clinical data collection, and robust automated analysis techniques are needed to fully demonstrate the potential of these rapidly evolving techniques.

Purpose

A recent meeting of international imaging experts sponsored by the International Spinal Research Trust (ISRT) and the Wings for Life Foundation (WfL) identified 5 state-of-the-art MRI techniques with potential to transform the field of spinal cord imaging by elucidating elements of the microstructure and function: diffusion tensor imaging (DTI), magnetization transfer (MT), myelin water fraction (MWF), MR spectroscopy (MRS), and functional MRI (fMRI).1,2 This review was designed to identify all relevant studies, summarize trends and commonalities of the methods employed, and determine the progress of these techniques in terms of clinical translation.

Methods

A systematic review of the English literature was conducted using MEDLINE, MEDLINE-in-Progress, Embase, and Cochrane databases to identify all human studies that investigated utility, in terms of diagnosis, correlation with disability, and prediction of outcomes, of these promising techniques in pathologies affecting the spinal cord. Studies were required to include at least 24 subjects in total and at least 12 with a specific pathological diagnosis. Two reviewers independently performed title/abstract review, full-text review, and data extraction, with discrepancies resolved by discussion. Data regarding study design, subject characteristics, MRI methods, clinical measures of impairment, and analysis techniques were extracted and tabulated to identify trends and commonalities. The studies were assessed for risk of bias, and the overall quality of evidence was assessed for each specific finding using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework.

Results

A total of 6597 unique citations were identified in the database search, and after full-text review of 274 articles, a total of 104 relevant studies were included (97% from the electronic search) (Figure 1). Among these, 69 studies utilized DTI and 25 used MT, with both techniques showing increased publications in recent years (Figure 2). The review also identified 1 MWF study, 11 MRS studies, and 8 fMRI studies. A total of 10 studies employed more than one advanced imaging technique, with 6 combining DTI and MT, 3 using DTI and MRS, and 1 employing DTI and fMRI. 16 of the DTI studies performed fibre tractography and 62 extracted metrics from regions of interest (ROIs), with 9 performed both types of analysis. Pathological conditions studied included multiple sclerosis (MS) (43 studies), cervical spondylotic myelopathy (CSM) (26 studies), amyotrophic lateral sclerosis (ALS) (11 studies), chronic spinal cord injury (SCI) (7 studies), non-specific compressive myelopathy (6 studies), non-specific myelitis (5 studies), acute SCI (3 studies), syringomyelia (3 studies), and neuro-myelitis optica (NMO) (2 studies). Most of the studies were exploratory in nature, lacking a priori hypotheses and showing a high (72%) or moderately high (20%) risk of bias, due to issues with study design, acquisition techniques, and analysis methods. The acquisitions for each technique varied widely across studies, rendering direct comparisons of metrics invalid. The DTI metric fractional anisotropy (FA) had the strongest evidence of utility, with moderate quality evidence for its use as a biomarker showing correlation with disability in several clinical pathologies, and a low level of evidence that it identifies tissue injury (in terms of group differences) compared with healthy controls (Table 1). However, insufficient evidence exists to determine its utility as a sensitive and specific diagnostic test or as a tool to predict clinical outcomes. Very low quality evidence suggests that other metrics also show group differences compared with controls, including DTI metrics mean diffusivity (MD) and radial diffusivity (RD), the diffusional kurtosis imaging (DKI) metric mean kurtosis (MK), MT metrics MT ratio (MTR) and MT cerebrospinal fluid ratio (MTCSF), and the MRS metric of N-acetylaspartate (NAA) concentration, although these results were somewhat inconsistent.

Discussion

State-of-the-art spinal cord MRI techniques are emerging with great potential to improve the diagnosis and management of various spinal pathologies, but the current body of evidence has only showed limited clinical utility to date. The majority of research to date has a high risk of bias related to technical factors and a paucity of carefully designed clinical studies. Among these imaging tools DTI is the most mature, but further work is necessary to standardize and validate its use before it will be adopted in the clinical realm.

Conclusions

The development of MRI techniques that can non-invasively characterize the microstructure and function of the spinal cord offers the possibility of improved diagnostic accuracy and clinical management of patients with various neurological disorders affecting the spine. Large, well-designed studies with a priori hypotheses, standardized acquisition methods, detailed clinical data collection, and robust automated analysis techniques are needed to fully demonstrate the potential of these rapidly evolving techniques.

Acknowledgements

No acknowledgement found.

References

1. Stroman, P.W., C. Wheeler-Kingshott, M. Bacon, J.M. Schwab, R. Bosma, J. Brooks, D. Cadotte, T. Carlstedt, O. Ciccarelli, J. Cohen-Adad, A. Curt, N. Evangelou, M.G. Fehlings, M. Filippi, B.J. Kelley, S. Kollias, A. Mackay, C.A. Porro, S. Smith, S.M. Strittmatter, P. Summers, and I. Tracey, The current state-of-the-art of spinal cord imaging: Methods. Neuroimage, 2014. 84(C): p. 1070-1081.

2. Wheeler-Kingshott, C.A., P.W. Stroman, J.M. Schwab, M. Bacon, R. Bosma, J. Brooks, D.W. Cadotte, T. Carlstedt, O. Ciccarelli, J. Cohen-Adad, A. Curt, N. Evangelou, M.G. Fehlings, M. Filippi, B.J. Kelley, S. Kollias, A. Mackay, C.A. Porro, S. Smith, S.M. Strittmatter, P. Summers, A.J. Thompson, and I. Tracey, The current state-of-the-art of spinal cord imaging: applications. Neuroimage, 2014. 84: p. 1082-93.

Figures

Flowchart showing results of literature search.

Chronological Trends in Clinical/Translational Studies Utilizing State-of-the-art Spinal Cord MRI Techniques

Evidence Summary with GRADE Ratings of Quality of Evidence



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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