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onset of MS during childhood or adolescence limits age-expected brain growth [3]. The
reduction in brain volume was not only global, but also more specifically notable in the
thalamus [4].
An initial acute demyelinating episode (or attack) may represent the first attack of MS,
where there will be clinical or MRI evidence of new lesions over time. Other children
have a monophasic transient illness and no new visible lesions over time, typified by
clinically isolated optic neuritis or transverse myelitis or by acute disseminated encepha-
lomyelitis (ADEM). The diagnosis of MS in children is typically rendered using the 2005
McDonald MS diagnostic criteria [5]. In children with monophasic demyelination, there
are no new visible lesions nor clinical attacks over time. In this latter group, we differen-
tiate the subjects with acute disseminated encephalomyelitis (termed ADEM group) from
the other subjects (termed MONO group) that may include optic neuritis or transverse
myelitis for example.
In this study, our goal was to investigate if there were any morphological characteris-
tics that could differentiate monophasic groups from the MS group and/or from normal
controls as early as possible after the first demyelinating attack to assist with diagnosis.
To find such characteristics, individual brain growth curves were fitted using all follow-
up data available. We analyzed the fitted curve to derive growth and volume metrics at
the time of the first attack to evaluate their prognostic value. Four individual relevant
metrics were computed and compared using z-scores with age-and-gender matched sub-
jects: the brain volume, the brain growth rate (slope of the curve at the time of first at-
tack), the normalized thalamus volume and the normalized thalamus growth rate.
2
Materials and Methods
2.1
Data
Subjects
85 patients were prospectively enrolled in the Canadian Pediatric Demyelinating Dis-
ease Study and were imaged at baseline (first demyelinating attack), and at 3, 6, and
12 months and annually thereafter (up to 8 years). All patients have been imaged on a
single 1.5T MRI scanner at The Hospital for Sick Children (HSC) in Toronto. Only
the MRI scans that passed a visual quality control process were included in the study
yielding a total of 520 scans for analysis. The first scan associated with the acute at-
tack was not included to avoid potentially confounding effects of acute inflammation
and steroid administration on brain volume changes.
The mean age at first attack was 11.42 years (range: 4.51-15.96 years). The follow-
up time (time between the first and the last scans) varied between 1.59 and 8.66 years
(mean: 4.33 years). At the time of this analysis, 23 patients were diagnosed with MS
according to the 2005 McDonald criteria
5
. 9 children had a single episode with the
presence of polyfocal neurological deficits and encephalopathy and were diagnosed as
ADEM. 53 subjects didn't meet clinical or MRI criteria for MS diagnosis or the diag-
nosis of monophasic ADEM and were included in the monophasic (MONO) group.
Twenty-three healthy, normally developing controls (termed here the NC group) were
recruited (18 female and 5 male; mean age at first scan 15.82 years, range 10.9-18.92
years) at the HSC site. The NC participants were scanned on the same scanner as the
patient group on two occasions, at intervals of 12 to 24 months.
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