Ultrasound imaging of patients with scoliosis

Scoliosis is a three-dimensional (3D) 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 3D morphology also involves the sagittal plane (i.e.
pathological lordosis) and transverse plane (i.e. increased axial rotation).
The varied causes of scoliosis are broadly classified as congenital,
neuromuscular, syndrome-related, idiopathic and spinal curvature due to
secondary reasons. The idiopathic scoliosis can be subdivided in infantile (0-3
years of age) juvenile (3-10 years of age) and adolescent (10-18 years of age)
scoliosis. The most common type, the adolescent idiopathic scoliosis (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. 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 (2D) representation of a
3D spinal deformity. Considering that biomechanical factors and the 3D
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 3D information to the surgeon.
Second, to monitor the deformity and detect possible curve progression,
patients with scoliosis 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 scoliosis 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 scoliosis 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, Simony et al. described the incidence of cancer
in the scoliosis patients 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, scoliosis 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. Additionally, some
syndromes are associated with a higher risk of scoliosis, like the 22q11.2
deletion syndrome. The University Medical Center Utrecht (UMCU) harbours a
specialized multidisciplinary outpatient clinic for children with 22q11.2
deletion syndrome. These patients are radiographically screened each two years
from the age of six, to detect a possible curve of the spine and are exposed to
the inevitable radiation as well, even without having scoliosis. Moreover, the
rehabilitation specialists sees a number neuromuscular syndromes that are
associated with an increased risk of scoliosis, such as Spinal Muscular
Atrophy. These patients receive often spinal radiographs to assess the curve
progression. Moreover, the rehabilitation specialists sees a number
neuromuscular syndromes that are associated with an increased risk of
scoliosis, such as Spinal Muscular Atrophy. These patients receive often spinal
radiographs to assess the curve progression.

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. Radiation-free imaging like 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 3D information. Recent advances in 3D
tracked ultrasound technology may enable this. 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. Previous studies showed that ultrasound is a valid and reliable
method for imaging of the scoliotic spine. However, most of these studies
included only mild AIS patients without previous surgery. In one of our
previous studies we also included mild AIS patients without previous surgery
and observed that the severity of the deformity in AIS patients can be assessed
by ultrasound imaging. However, further research is needed to determine if
ultrasound can be used in a clinical setting for all scoliosis patients and
patients that are referred for scoliosis (without having a scoliosis), to see
whether the ultrasound imaging could is reliable and valid in detecting
scoliosis.

Primary Objective: the primary objective of this study is to investigate the
accuracy and reliability of coronal curve ultrasound measurements in patients
with scoliosis as well as the accuracy and reliability of ultrasound imaging to
detect scoliosis (Cobb angle > 10°) in patients that are suspected of having
scoliosis. The ultrasound imaging will be compared with the standard
radiographic measurements obtained at the same consultation, at the first visit
as well as the follow-up visits.
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 in both 2D and 3D measurements. The secondary objectives are based
on the sagittal and the transverse plane; the thoracic kyphosis and lumbar
lordosis and the apical vertebral rotation. All these measurements will be
compared between the ultrasound and radiography. To test the intra- and
interobserver variability, 20 patients will receive 3 scans at the first visit
(2 by observer 1 and 1 by observer 2).

This prospective cohort study is initiated and coordinated by the Department of
Orthopaedic Surgery from the UMCU, the Netherlands. The ultrasound device,
Scolioscan®, is a unique ultrasound device developed for measuring the
curvature of the scoliotic spine. The coordinating researcher completed the
Scolioscan® training already.

Normally, spinal X-rays are made of patients with scoliosis, and patients
suspected of having scoliosis during an orthopaedic consultation. These X-rays
are required to diagnose a scoliosis and to monitor the possible 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 ultrasound
examinations at certain intervals to determine the progression of the curve.
These intervals coincide with the regular outpatient visits, with a maximum of
four examinations in two years.

After obtaining informed consent, the 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 3D 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 scoliosis doctor will determine
the thoracic and lumbar Cobb angle, thoracic kyphosis, lumbar lordosis and
rotation on routine radiographs without knowledge of the ultrasound outcomes.
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, tThe only addition to the regular procedure is the radiation-free
ultrasound imaging of the spine that will be obtained at different visits for
each included patient. Most X-rays are made in straight standing (or sitting)
position. However, for operative planning, side bending X-rays will be made. 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. Furthermore, the intra- and interobserver
reliability will be tested using 20 patients of each group at their first
visit. For these measurements, the first observer will scan the patients twice
and the second observer will scan the patients once. In total, these 20
patients receive three scans each at their first visit.

This study includes four groups of patients, based on the cause of the
scoliosis; idiopathic, neuromuscular, congenital and syndrome-related. Five to
ten patients meet the inclusion criteria each week at different outpatient
clinics in the UMCU. Some of these patients are screened on scoliosis because
they have some syndromes (like the 22q11.2 deletion syndrome) and are more
likely to have a scoliosis. These screening programmes start at the age of six
years. Therefore, the minimum inclusion age is six years. To include the
required number of patients (256 patients), one year seems more than adequate.
After this first year, all the patients are probably included, thereafter we
will scan the patients for the second time, and eventually third and fourth
time, at their regular visit.

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.