DTI of the Brain and Cervical Spine: Evaluation in Normal Subjects and Patients With Cervical Spondylotic Myelopathy
Condition: Cervical Spondylosis With Myelopathy
MeSH terms: Spondylosis; Spinal Cord Diseases; Bone Marrow Diseases
Study type: Observational

Summary: 
      More than half of the middle-aged population has radiologic evidence of cervical spondylosis
      (Irvine 1965) and a subset of this population develops cervical spondylotic myelopathy (CSM),
      a condition in which the spinal cord is impaired, either by direct mechanical compression or
      indirectly by arterial deprivation and/or venous stasis. In this study we aim to test the
      hypothesis that diffusion tensor imaging can provide prognostic information on the integrity
      of the spine in these patients which is unavailable from conventional MRI images
    

Detailed description: 
      More than half of the middle-aged population has radiologic evidence of cervical spondylosis
      and a subset of this population develops cervical spondylotic myelopathy (CSM), a condition
      in which the spinal cord is impaired, either by direct mechanical compression or indirectly
      by arterial deprivation and/or venous stasis. Although many operations are performed for
      conditions related to CSM, no consensus exists regarding the timing of the surgical
      intervention or how to select among the available surgical options for a given patient. Many
      factors have been implicated in the propensity for CSM to develop including advanced age,
      disability at presentation, cord diameter, cord area, altered cord signal on MRI (T2- and T1-
      weighted images), increased cervical spinal mobility and a congenitally narrow spinal canal.
      The same factors may also determine the response to surgery, either positively (increased
      cervical mobility) or negatively (advanced age, congenitally narrow spinal canal). The
      potential complications of surgical procedures are noteworthy. Although incapacitating
      adverse effects are uncommon, their occurrence in a disease process with a potentially benign
      course is of undoubted gravity. Finally, it should be noted that the radiologic criteria of
      cervical root or cord compression on MRI are subjective and it is uncertain that they
      correlate with the clinical symptoms.

      Diffusion tensor imaging (DTI) is sensitive to the motion of water and is considered to be a
      marker for axonal integrity in the brain. There has been much interest in applying the
      technique to the spine and in particular to the evaluation of patients with CSM. In the brain
      DTI is performed using a single shot echo planar imaging (SS-EPI) sequence which acquires all
      of the data for a single slice following the application of a single excitation pulse and
      diffusion gradients. While very efficient in terms of data collections there are several
      problems with SS-EPI, notably that 1) It is best suited to the acquisition of relatively
      small imaging matrices, resulting in either low spatial resolution or the use of additional
      techniques to reduce the field of view (FOV). Increasing the number of echoes acquired to
      increase the resolution does not produce an increase in the acquired resolution since the
      decay of the signal during the longer echo train results in increased blurring of the image.
      2) The images are distorted by susceptibility gradients in areas close to the interfaces
      between tissue and bone or osseous structures. These factors have made applying DTI to
      clinical studies of the spine problematic. Specifically:-

        1. The small size of the spinal cord means that high spatial resolution is required.

        2. The susceptibility effects from the surrounding osseous structure result in image
           distortion.

        3. The motion of the cord during the cardiac cycle leads to artifacts.

      Readout segmented EPI (RESOLVE or RS-EPI) sequence has been shown to be capable of obtaining
      images with higher spatial resolution and reduced distortion in the brain. We have recently
      demonstrated that the RESOLVE sequence can also be used to obtain high quality DTI images of
      the cervical spine of volunteers (see figure 1) and can provide clinically useful information
      in subjects with metastases in the spine. The RESOLVE sequence breaks the data collection
      into several segments, resulting in reduced distortion and the potential to obtain images
      with higher resolution, but at the cost of either increased scan time or a reduced number of
      directions for the diffusion gradients (i.e. reduced signal to noise ratio (SNR)). The
      RESOLVE sequence also incorporates real-time assessment of the data, enabling data corrupted
      by motion to be rejected and then reacquired. We now wish to optimize, and assess the
      clinical utility of, the RESOLVE sequence in patients with CSM by applying it to a group of
      CSM patients and a group of aged matched control subjects. The raw diffusion images are
      post-processed to yield parametric images which characterize the diffusivity (mean,
      longitudinal and radial) and anisotropy (directional dependence) of the diffusion. The
      anisotropy of the diffusion data is typically quantified using the fractional anisotropy (FA)
      index, however, we have recently shown that two other quantities, the mode and ellipsoidal
      area ratio (EAR) of the diffusion tensor, provide useful supplementary information and we
      propose to use all three parameters when analyzing the anisotropy of the diffusion data from
      this study.

      Using the RESOLVE sequence address these first two of the "bullet" points listed above and we
      found that in some subjects high quality DTI images of the spine can be obtained without the
      use of cardiac gating, however, for a robust clinical sequence we, and other groups, have
      found cardiac gating to be essential. Another issue to consider for DTI studies of the spine
      is the orientation of the scan. Sagittal images provide coverage of the whole spine with
      relatively few slices, which is particularly beneficial when cardiac gating is employed.
      Axial slices have the advantage that the changes in the configuration of the spine in the
      caudal-cranial direction are relatively slow, meaning that thicker slices can be used without
      a significant loss of information. However, a relatively large number of slices are still
      required to cover the entire C-spine resulting in a lengthy measurement time when cardiac
      gating is used.

      Objectives The investigators wish to try and answer the following questions for the C-spine:-

        1. What are the diffusion characteristic of the normal C-spine (spatial variation and age
           dependence)?

        2. How do the RESOLVE and SS-EPI images of the spine compare in terms of image quality?

        3. What is the effect of changing the number of segments for the RESOLVE sequence?

        4. When comparing SS-EPI and RESOLVE are there statistically significant differences in the
           derived values of anisotropy or diffusivity?

        5. Are the diffusion characteristics of the C-spine of subjects with CSM significantly
           different from those of aged matched controls?

        6. Can DTI of the spine be used to derive diagnostic information, either in terms of
           prognostic information for individual CSM patients or the identification of sub-groups
           of CSM patients? For the brain the question we would be addressing are:-

      1) When comparing SS-EPI and RESOLVE are there statistically significant differences in the
      derived values of anisotropy or diffusivity? 2) Is there a statistically significant
      difference in the volume of the fiber tracts derived using the two sequences or between the
      two groups? 3) Is the diffusion data from the brains of patients with CSM significantly
      different from that of the controls?
    

Observational model: Case-Control
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Patients at the Emory Orthopaedics & Spine Center suffering signs and symptoms of cervical
        myelopathy and with evidence of radiographic cervical cord compression with or without
        abnormal spinal cord signal intensity secondary to spondylosis.
      
Keywords: Magnetic resonance imaging (MRI); Diffusion tensor imaging; Spine