Esther Ruberte1, Tim Sinnecker1,2, Michael Amann1,3, Yvonne Naegelin2, Iris-Katharina Penner4, Matteo Pardini5, Jens Kuhle2, Tobias Derfuss2, Christoph Stippich3, Ludwig Kappos2, Jens Wuerfel1, and Özgür Yaldizli1,2
1Medical Image Analysis Center AG, Basel, Switzerland, 2Department of Neurology, Universitätsspital Basel, Basel, Switzerland, 3Department of Neuroradiology, Universitätsspital Basel, Basel, Switzerland, 4Department of Neurology, University Hospital Düsseldorf, Düsseldorf, Germany, 5Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa and IRCCS S. Martino-IST, Genoa, Italy
Synopsis
As pars pro
toto, lateral ventricle enlargement might give an indirect estimate of brain atrophy.
In contrast to whole brain atrophy, ventricle
enlargement is, however, clinically easy to assess and its
quantification is robust to MR images of less than perfect quality. Here we
investigate i) the applicability of an automatic lateral ventricle delineation
algorithm (ALVIN) in multiple sclerosis (MS), and ii) the association between of
lateral ventricle enlargement and clinical disability in MS longitudinally.
We found that ALVIN reliably estimates the lateral ventricle volume in MS that is
associated with whole brain atrophy and neurological as well as cognitive
disability.
Introduction
As pars pro toto, lateral ventricle enlargement
might give an indirect estimate of brain atrophy. In contrast to whole brain
atrophy, ventricle enlargement is, however,
clinically easy to assess and its quantification is robust to MR images
of less than perfect quality. Here we investigate i) the applicability of an automatic
lateral ventricle delineation algorithm (ALVIN) in multiple sclerosis (MS), and
ii) the association between of lateral ventricle enlargement and clinical disability
in MS longitudinally.Methods
In total, 127
patients with relapsing-remitting (n=101), secondary-progressive (n=22) or primary-progressive
(n=4) MS with 5 years follow-up were derived from a longitudinal MS cohort on
the phenotype-genotype characterization of MS. Brain MRI was obtained on a 1.5 Tesla MRI system (Magnetom
Avanto, Siemens Medical Solutions). The brain MRI protocol included high-resolution
three dimensional T1-weighted (T1w) magnetization prepared rapid gradient echo (MPRAGE,
repetition time (TR) 2100ms, echo time (TE) 3.9ms, inversion time (TI) 1100ms,
flip angle 15°, isotropic resolution of 1 mm3, acquisition time 9
minutes), and a pre-contrast double echo proton density- and T2-weighted
sequence (axial, spatial resolution 0.98x0.98x3mm3). ALVIN1 was used to calculate the normalized lateral
ventricle volume (LVV) in comparison to a manual segmentation by applying a
binary mask to spatially normalized lesion-filled cerebrospinal fluid (CSF)
segmented images. T1w hypointense and T2-weighted (T2w) hyperintense lesions
were marked using Amira (Mercury Computer Systems Inc., Chelmsford, USA).
Lesion filling was done by using “lesion_filling” as part of the FMRIB Software
Library (FSL, version 5.0, Oxford, UK).2 To estimate normalized brain volume (NBV), SIENAX was
applied.3, 4 Neurological and cognitive disability was assessed
using the Expanded Disability Status Scale (EDSS),5 the Multiple Sclerosis Functional Composite (MSFC)6 and the Paced
Auditory Serial Addition Test (PASAT).7
Finally, the
scan-re-scan reliability was assessed by using a two way mixed intraclass
correlation model of absolute agreements and single measures to calculate an intraclass
correlation coefficient (ICC). Since all variables other than disease duration
and age were not normally distributed, any associations between LVV or LVV
change and clinical outcomes or NBV were investigated by using non-parametric Spearman
correlation.Results
At baseline,
mean LVV was 29.7±14.2 ml and correlated with age (rho=0.223, p=0.012), disease
duration (rho=0.391, p<0.001), EDSS (rho=0.457, p<0.001), MSFC
(rho=-0.451, p<0.001), PASAT (rho=-0.249, p=0.005), T1 lesion volume (rho=0.553,
p< 0.001), T2 lesion volume (rho=0.558, p< 0.001) and NBV (rho=-0.591;
p< 0.001).
The agreement
between ALVIN LVV and a manual lateral ventricle segmentation was high (intra-class
correlation coefficient (ICC) = 0.991, mean difference 1.15±1.56 ml, range
-5.3ml – 6.0ml). In addition, lateral ventricle enlargement was associated with
an increase in T1w and T2w lesion volume, NBV reduction and a worsening of the
PASAT score. In detail, the mean LVV increased by 3.6±4.6 ml over 5 years
corresponding to a mean annual LVV change of 0.7 ml (2.4%, figure 1).Conclusion
ALVIN reliably estimates the LVV in MS that is
associated with whole brain atrophy and neurological as well as cognitive
disability.Acknowledgements
No acknowledgement found.References
1. Kempton MJ, Underwood TS, Brunton S,
et al. A comprehensive testing protocol for MRI neuroanatomical segmentation
techniques: Evaluation of a novel lateral ventricle segmentation method.
Neuroimage 2011;58:1051-1059.
2. Battaglini
M, Jenkinson M, De Stefano N. Evaluating and reducing the impact of white
matter lesions on brain volume measurements. Hum Brain Mapp 2012;33:2062-2071.
3. Smith
SM, Jenkinson M, Woolrich MW, et al. Advances in functional and structural MR
image analysis and implementation as FSL. Neuroimage 2004;23
Suppl 1:S208-219.
4. Smith SM, Zhang Y, Jenkinson M, et al.
Accurate, robust, and automated longitudinal and
cross-sectional brain change analysis. Neuroimage 2002;17:479-489.
5. Kurtzke
JF. Rating neurologic impairment in multiple sclerosis: an expanded disability
status scale (EDSS). Neurology 1983;33:1444-1452.
6. Fischer
JS, Rudick RA, Cutter GR, Reingold SC. The Multiple Sclerosis Functional
Composite Measure (MSFC): an integrated approach to MS clinical outcome
assessment. National MS Society Clinical Outcomes Assessment Task Force. Mult
Scler 1999;5:244-250.
7. Gronwall DM. Paced auditory
serial-addition task: a measure of recovery from concussion. Percept Mot Skills
1977;44:367-373.