Clinical Trial Details
— Status: Withdrawn
Administrative data
| NCT number |
NCT01382290 |
| Other study ID # |
MRI DIffusion Spine |
| Secondary ID |
|
| Status |
Withdrawn |
| Phase |
N/A
|
| First received |
September 13, 2005 |
| Last updated |
August 5, 2016 |
| Start date |
March 2008 |
| Est. completion date |
December 2009 |
Study information
| Verified date |
August 2016 |
| Source |
Children's Healthcare of Atlanta |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
United States: Institutional Review Board |
| Study type |
Interventional
|
Clinical Trial Summary
Diffusion-weighted (DW) magnetic resonance imaging (MRI) imaging is a well established
method for detecting acute injury to the brain and is used on all children undergoing an MRI
brain scan at Children's Healthcare of Atlanta. The possibility of using DW MRI to study
other areas of the body, such as the spinal cord, has been recognised as having great
clinical potential. However, two main problems have hindered the clinical application of the
technique; firstly, the extreme motion sensitivity of the technique meant that respiratory
motion have hampered clinical studies. Secondly, the close proximity of the spinal cord to
the bones in the spinal column complicates the application of the techniques developed for
the brain to the spine. Recently, several techniques have been developed which address these
problems and these are now available on the MRI scanners used at Children's Healthcare of
Atlanta.
We now wish to evaluate how well these techniques work on children in a routine clinical
setting. For this reason we wish to add a single scan of the spine to the imaging protocol
of children receiving a routine scan of the brain or spine. This will permit us to evaluate
the image quality in both normal and abnormal spines. We plan on enrolling 60 patients with
normal spines and 30 patients with abnormal spines. No additional sedation and/or contrast
will be required and the additional imaging time for the diffusion studies will be less than
10 minutes. Parental consent will be a pre-requisite for any patient to be enrolled into the
study.
Description:
Background and significance
Diffusion-weighted (DW) magnetic resonance imaging (MRI) imaging is a well established
method for detecting acute ischaemic injury in the brain and is being increasingly applied
to the study of brain structure and organisation (1,2). The technique provides information
on the motion of water molecules and uses no ionising radiation. The possibility of using DW
MRI to probe neuronal microstructures in highly ordered neuronal systems, such as the spinal
cord, has been recognised as having great clinical potential. However, the combination of
susceptibility artefacts from the surrounding bony structures, motion of the cerebrospinal
fluid (CSF), carotid and vertebral artery pulsations and respiratory motion have hampered
clinical studies. Recently, several techniques have been developed to address these problems
(3,4) and two of these methods will shortly be available for use at the Scottish Rite campus
of CHOA.
We propose to apply DW imaging of the spine to the following groups of patients :
1. Patients with tethered cords.
2. Patients with Chiari I malformations.
3. Normal children undergoing a MRI of the spine.
All of the studies would be performed on children who have already been referred for a MRI
and the diffusion sequences would be performed after the requested MRI exam is complete. No
additional sedation and/or contrast would be required. Informed consent would be requested
from the parents for all of these studies. The additional imaging time required for the
diffusion studies would be less than 10 minutes. We plan on enrolling 60 patients with
normal spines and 30 patients with abnormal spines in this study.
Tethered cord. Tethered spinal cords are a group of complex developmental malformations of
the spinal cord of which the most common cause is children with repaired spina-bifida or
myelomeningocele. Although these are usually operated on shortly after birth, all repaired
myelomeningoceles have some degree of tethering. The basic problem is exacerbated because as
children grow their spinal cords do not grow as quickly as their spinal columns, so the
spinal cord must be able to freely ascend on the inside of the spinal column during growth.
If various abnormal structures are holding onto the spinal cord from below it stretches the
spinal cord, leading to chronic local ischaemia, which can in turn lead to a progressive
loss of function. The signs and symptoms associated with cord tethering are often
non-specific and are poorly understood. Diffusion MRI may be very useful in the monitoring
of tethered cords since initial studies on adults with cervical spondylosis have implied
that it is more sensitive than conventional MRI imaging in depicting pathological changes
within the spinal cord. Hence diffusion MRI has the potential to be a more sensitive method
of determining if the cord is under stress due to tethering and hence in need of surgery.
Chiari I malformation A Chiari I malformation is a condition characterised by an abnormal
inferior projection of the cerebellar tonsils through the foramen magnum, into the upper
cervical spinal canal. If the degree of projection is small then the condition is generally
referred to as tonsilar ectopia. Chiari I malformations may be associated with other
anomalies, most commonly hydrosyringomyelia (which in turn can lead to neurologic deficits
and scoliosis) and hydrocephalus. Symptoms of a Chiari I malformation most often begin
during infancy, although they may be delayed until adolescence or adulthood. Symptoms are
often non-specific and usually include headache, vomiting, muscle weakness in the head and
face, difficulty swallowing, and varying degrees of mental impairment. Paresis or paralysis
of the arms and legs may also occur. As they grow older, adolescents and adults with Chiari
I malformation who previously were asymptomatic may show signs of progressive brain
impairment, such as involuntary, rapid, downward eye movements. The pathophysiology of
syrinx development (hydrosyringomyelia) is understood to be a state of chronic interstitial
edema of the spinal cord due to an accumulation of extracellular fluid.
A diagnosis of Chiari I malformation is generally made using a conventional MRI scan and is
often an incidental finding during an evaluation of other abnormalities, making an
interpretation of the significance of the imaging findings difficult. Patients that have
symptoms which potentially indicate abnormally positioned tonsils can have normal imaging
findings, tonsilar ectopia or mild Chiari I malformation. In the case that the cerebellar
tonsils are not clearly abnormal, according to our conventional imaging diagnostic criteria,
it can be difficult to determine the cause of the symptoms. They may be caused by the low
tonsils, in which case a surgical decompression would be performed, or they may simply be
incidental findings.
A further problem in determining a strategy for managing patients with a Chiari I
malformation is that the criteria for surgical intervention are nebulous. Some patients are
symptomatic with only a minor degree of tonsillar ectopia and others with severe
displacement of the cerebellar tonsils into the upper spinal canal have no symptoms. Since
the correction of a Chiari I malformation requires surgery it is generally reserved for
patients showing clear evidence of progressive clinical symptoms. Any technique that can
provide information on pathological changes within the spinal cord would be a very important
complement to the clinical data and the anatomical information provided by conventional MRI.
At present it is difficult to predict which patients are predisposed to developing
syringomyelia on the basis of conventional imaging findings alone and DW-MRI may be able to
provide useful complementary information.
Normal patients. To date the only information regarding the values for diffusion within the
spinal cord comes from a limited number of studies on normal, adult, volunteers. It is known
that the diffusion properties of the brain vary significantly with age and it is expected
that the diffusion properties of the spine will show a similar variation. Thus, in order to
be able to properly interpret the results of the studies on children with suspected
pathology it is necessary to have a control group in order to allow normal values for
different age ranges to be established.
