Ultrasound imaging of adolescent idiopathic scoliosis (The Scolioscan)

Adolescent idiopathic scoliosis (AIS) is a three-dimensional (3-D) deformity of
the spine and the entire trunk, involving changes in all three planes. Although
officially defined by the Scoliosis Research Society as a lateral curve of more
than ten degrees Cobb angle, its true 3-D morphology also involves the sagittal
plane (i.e.pathological lordosis) and transverse plane (i.e. increased axial
rotation. AIS has a prevalence of 1.5-3% within the general population of
children aged 10-18 years. Typically girls are affected more frequently with a
sex-ratio of 5.4:1 for curves of 20° or more.

Traditionally, standing conventional radiographs (X-rays) of the entire spine
are the gold standard for the assessment of scoliosis, as well as for clinical
follow-up and treatment decision making. It is since the discovery of this type
of radiation by Wilhelm Röntgen in the early 20th century, that this field of
orthopaedic surgery has evolved significantly and ultimately even improved both
conservative (e.g. brace) and surgical treatment. However, despite these
advancements, there are several disadvantages of this imaging method. First, an
X-ray, typically performed in two directions (posterior-anterior and lateral)
is a two-dimensional (2-D) representation of a 3-D spinal deformity.
Considering that biomechanical factors and the 3-D orientation of the vertebrae
in space were shown to play a role in scoliosis initiation and progression and
are important for determining surgical strategy, this technique falls short of
providing this 3-D information to the surgeon. Second, to monitor the deformity
and detect possible curve progression, AIS patients are exposed to an ionizing
radiation X-ray at least each 4 to 6 months. Previous studies have demonstrated
that X-rays bring an inevitable exposure of repeated doses of ionizing
radiation. Considering the frequency of X-ray imaging, the exposed organs, the
young age of the patients, their susceptibility for ionizing radiation and
remaining life span, this technique has been shown to increase the risk for
developing malignancies. The risk for breast cancer is increased with 4.2% for
AIS patients as compared to the general population. Furthermore, once this
diagnosis is established there is 70% more mortality in these patients due to a
more aggressive nature of the tumour. The overall risk for the development of a
solid malignancy is 2% higher in the AIS group as compared to the general
population. All these data are only based on X-ray imaging; in certain cases
additional imaging with computed tomography (CT), which has a much higher
exposure of ionizing radiation, is necessary and this will certainly increase
this risk even more. Recently, a study described the incidence of cancer in the
AIS cohort to be 17 times greater than the incidence of 0.25 % in an age-sex
matched non-scoliotic cohort. Once eventual treatment is completed, AIS
patients are still exposed to ionizing radiation to evaluate the effect of
treatment and to rule out curve deterioration, pseudarthrosis, metal failure
and other complications.

The progression of the scoliotic curve is monitored by using the Cobb angle,
which measures the angle between the two most tilted vertebrae in opposite
directions on standing X-rays. Magnetic resonance imaging (MRI) is performed
supine and is primarily used to rule out intraspinal anomalies (e.g. syrinx,
Arnold-Chiari malformation, tethered cord).
A new method is obviously needed, which is safe, non-radiating, fast, easy to
use, cheap and preferably should provide 3-D information. Recent advances in
3-D tracked ultrasound technology may enable this. Also, once its reliability
has been proven, this new method could be used in mass screening for early
intervention for scoliosis, which is not ethical to do with regular X-rays.

Although a number of phantom and pilot studies have been performed, measuring
certain characteristics of the AIS spine by using ultrasound, its clinical
application so far has been very limited. Further research is needed to
determine if ultrasound can be reliably used in a clinical setting, either as
the primary modality for assessing scoliosis, or to monitor the progression of
scoliosis following initial radiographic assessment. Based on a new
collaboration with the CHU Sainte Justine Hospital (Montreal, Canada) it is
possible to make a 3D reconstruction out of the two 2D radiographs. This will
give us the opportunity to compare the ultrasound with the radiograph with
greater accuracy.

The primary objective of this study is to investigate the accuracy and
reliability of ultrasound scoliosis measurements and progression of the curve
and to correlate these outcomes with the standard radiographic measurements
obtained at the same consultation in both 2D and 3D measurements.

The measurements consist of:
- The primary and secondary Cobb angles; the angle between the two most tilted
vertebrae in the coronal plane of the lateral curve of the spine
- The thoracic kyphosis and lumbar lordosis
- The apical vertebral rotation

To investigate the accuracy, the ultrasound measurements will be compared to
the measurements determined by radiographs (gold standard). To determine the
reliability of the measurements, after obtaining the ultrasound image, each
patient is measured three times in a row. The first one by observer 1, the
second time by observer 2 and the third time by observer 1 again. Thus, we will
establish the intra- and interobserver reliability at twenty patients. The same
procedure will be repeated at their next regular visits (with a maximum of 4
scanmoments) to determine whether the ultrasound device is able to measure
progression of the curve. The first ultrasound image, made by observer 1, will
be used for radiographs comparison.

This prospective cohort study is initiated and coordinated by the Department of
Orthopaedic Surgery from the University Medical Centre Utrecht (UMCU), the
Netherlands. The aim of this single-center study is to determine the
reliability of ultrasound in diagnosing scoliosis, as compared to conventional
X-rays, which are the standard of care. The ultrasound device, Scolioscan®, is
a unique ultrasound device developed for measuring the curvature of the
scoliotic spine.

Normally, AIS patients undergo conventional radiographs of the spine during a
consultation by the orthopaedic surgeon at least each 4 to 6 months. These
X-rays are required to diagnose a scoliosis and to check for progression of the
curve. During the X-ray we will place a small belt around the waist of the
patient in order to make the 3D reconstruction. The Cobb angle is used to
express the scoliosis in the coronal plane. Furthermore, the thoracic kyphosis
and lumbar lordosis are determined to describe the sagittal alignment. In this
study the patients are examined by ultrasound at the same day as the
radiographs is taken. Each included patient will receive two ultrasound
examinations at certain intervals to determine the progression of the curve.
These intervals coincide with the regular outpatient visits.

After obtaining informed consent, the AIS patients will be examined by using
the radiation-free ultrasound device (the Scolioscan®), on the same day as the
radiograph is made and prior to the outpatient visit. The Scolioscan® software
is able to provide a 3-D image of the scoliotic spine from which can be derived
the primary and secondary Cobb angles, thoracic kyphosis, lumbar lordosis and
vertebral rotation. Prior to consultation, the orthopaedic surgeon will
determine the thoracic and lumbar Cobb angle, thoracic kyphosis, lumbar
lordosis and rotation on routine radiographs without knowledge of the
ultrasound outcomes. Most X-rays are made in straight standing (or sitting
position). However, for operative planning, side bending X-rays will be made as
well. If the X-rays are made in side bending position, the ultrasound scans
will be made in side bending position as well, since the ultrasound scans are
made in the same position as the X-rays. Moreover, the radiographs will be
anonymously extracted from PACS in order to make the 3D reconstruction with the
use of the Clindexia and NewSpine3D software. So, the only addition to the
regular procedure is the radiation-free ultrasound imaging of the spine that
will be obtained two times at two different visits for each included patient.

Each month there are twenty to thirty new AIS patients at our outpatient
clinic. To include the required number of patients (n=110), the study period
seems sufficient.

The overall risks of the ultrasound device are the same as the regular
ultrasound devices that are widely used. To make sure there are no other
possible risks, our technical department (MTKF) will check the complete
procedure and device.