DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY
ORIGINAL ARTICLE
Diffusion tensor imaging in pediatric Chiari type I malformation TADESSE ESHETU 1
| AVNER MEODED 2 | GEORGE I JALLO3 | BENJAMIN S CARSON 3 | THIERRY AGM HUISMAN 2 | ANDREA PORETTI 2 1 Division of Neuroradiology, The Russell H Morgan Department of Radiology and Radiological Science, The Johns Hopkins School of Medicine, Baltimore, MD; 2 Section of Pediatric Neuroradiology, Division of Pediatric Radiology, The Russell H Morgan Department of Radiology and Radiological Science, The Johns Hopkins School of Medicine, Baltimore, MD; 3 Division of Pediatric Neurosurgery, The Johns Hopkins School of Medicine, Baltimore, MD, USA. Correspondence to Andrea Poretti, Section of Pediatric Neuroradiology, Division of Pediatric Radiology, The Russell H Morgan Department of Radiology and Radiological Science, The Johns Hopkins School of Medicine, Charlotte R Bloomberg Children’s Center, Sheikh Zayed Tower, Room 4174, 1800 Orleans Street, Baltimore, MD 21287-0842, USA. E-mail: [email protected]
PUBLICATION DATA
Accepted for publication 27th March 2014. Published online ABBREVIATIONS
C1M CST DTI MCP ROI
Chiari type I malformation Corticospinal tract Diffusion tensor imaging Middle cerebellar peduncle Regions of interest
AIM Chiari type I malformation (C1M) may be symptomatic or asymptomatic as an incidental finding. In this retrospective study, we applied diffusion tensor imaging (DTI) to study the brainstem and cerebellar white matter tracts in C1M. METHOD Diffusion tensor imaging (DTI) data were acquired on a 1.5T MR-scanner using balanced pairs of diffusion gradients along 20 non-collinear directions. Measurements from regions of interest in each pontine corticospinal tract, medial leminscus, and middle cerebellar peduncle (MCP) and in the lower brainstem were obtained for fractional anisotropy and mean, axial, and radial diffusivity. Values in symptomatic and asymptomatic children, and children with and without hydromyelia were compared using analysis of variance. RESULTS Fifteen children with C1M (10 males, five females; six symptomatic [four with hydromyelia] and nine asymptomatic) were included. Median age was 6 years 5 months (range 2y 10mo–15y 4mo). No significant differences in DTI scalars were found in the lower brainstem. In both MCPs, axial diffusivity values were lower in symptomatic than in asymptomatic children (p=0.049 and p=0.035 respectively) and higher in children with hydromyelia versus without hydromyelia (p=0.018 and p=0.006 respectively). In the left MCP, mean diffusivity values were lower in symptomatic than in asymptomatic children (p=0.047). INTERPRETATION Our results show that microstructural tissue alterations may be present in C1M. Additionally, our study suggests a specific role for the MCPs in C1M. Further largescale studies are warranted.
INTRODUCTION Chiari I malformation (C1M) is a hindbrain abnormality characterized by ectopia/herniation of at least one cerebellar tonsil 5mm or more below the foramen magnum.1,2 The cerebellar tonsils are usually pointed or ‘peg shaped’. Associated neuroimaging findings may include a small posterior fossa, stretching of the fourth ventricle, shallow retrocerebellar cerebrospinal fluid (CSF) space, hydrocephalus, hydrosyringomyelia, cervico-medullary kinking, and bony deformities of the craniocervical junction.1,2 Children with C1M may present with a variety of neurological symptoms including occipital headaches exacerbated by Valsalva or sudden postural change, neck pain, visual disturbance, vertigo, and dizziness.1,3 However, with the progressing availability of diagnostic magnetic resonance imaging (MRI), children with asymptomatic C1M have increasingly been identified. Their diagnoses are typically made as an incidental finding on brain MRI studies obtained for various unrelated indications.3,4 © 2014 Mac Keith Press
Diffusion tensor imaging (DTI) is an advanced magnetic resonance technique that allows the study of the internal neuroarchitecture in vivo by measuring the three-dimensional shape and direction of diffusion in the brain.5 DTI is based on the directional movement of water, which is determined by the brain microstructure and imaged with diffusion-sensitive MRI sequences to generate virtual, threedimensional representations of the white matter fiber tracts. The diffusion tensor is a mathematical description of the magnitude and directionality (anisotropy) of the movement of water molecules in three-dimensional space. By measuring the complete tensor of the diffusion, various DTI parameters including the degree of anisotropic diffusion can be calculated. Decreased fractional anisotropy values in white matter tracts reflect injury with disorganized or disrupted myelin sheaths.6 Diffusion tensor imaging is, therefore, a suitable magnetic resonance tool to evaluate qualitatively and measure quantitatively the microscopic integrity of white matter structures within the brain tissue DOI: 10.1111/dmcn.12494 1
in congenital and acquired disorders of the pediatric brain.6,7 The aim of this study was to investigate the integrity of brainstem and cerebellar white matter tracts using DTI in children with C1M confirmed by anatomical MRI. We hypothesized decreased integrity/chronic injury of the white matter tracts in the lower brainstem in symptomatic compared to asymptomatic children, and in children with hydromyelia compared to children without hydromyelia.
METHOD This retrospective study was approved by the institutional research ethics board of The Johns Hopkins School of Medicine. Participants The inclusion criteria for this study were (1) confirmed diagnosis of C1M (herniation/ectopia of at least one cerebellar tonsil 5mm or more below the line drawn from the basion to the opisthion); (2) no association with other disorders such as Klippel-Feil or Costello syndrome;8 (3) for the children who underwent decompressive surgery, availability of presurgical DTI data without artifacts enabling a high quality DTI post-processing; and (4) age 18 years or younger at MRI diagnoses. Eligible patients were recruited through an electronic search of our pediatric neuroradiology database covering the period between 1 September 2010 and 31 March 2012. Review of the clinical charts provided detailed information about neurological features of the children. The symptomatic stage was defined according to Tubbs et al.1 and Aiken et al.9 Hydromyelia was defined as a dilatation of the central canal. The presence or absence of hydromyelia was assessed on axial and sagittal T1- and T2-weighted images of the spine. Diffusion tensor imaging All MRI studies were performed on a 1.5T scanner (Siemens Avanto, Erlangen, Germany) using our standard departmental protocol including 3D-T1- and axial T2-weighted images, an axial fluid attenuation inversion recovery sequence as well as a single shot spin echo, echo planar axial DTI sequence with diffusion gradients along 20 non-collinear directions. An effective high b-value of 1000s/mm2 was used for each of the 20 diffusion-encoding directions. We performed an additional measurement without diffusion weighting (b = 0s/ mm2). For the acquisition of the DTI data the following parameters were applied: repetition time (TR) = 7100ms; echo time (TE) = 84ms; slice thickness = 2.5mm, field-ofview (FOV) = 240 9 240mm and matrix size = 192 9 192. Parallel imaging iPAT = 2 with generalized auto-calibrating partial parallel acquisition reconstruction was used. The acquisition was repeated twice to enhance the signal-to-noise ratio. Additional axial and sagittal T1- and T2-weighted images of the spine were acquired according to our standard departmental protocol. 2 Developmental Medicine & Child Neurology 2014
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What this paper adds Significant differences in axial diffusivity of the middle cerebellar peduncles were found in children with symptomatic versus asymptomatic Chiari type I malformation (C1M) as well as children with CIM with and without hydromyelia.
Image analysis Diffusion tensor imaging data of the children were transferred to an offline workstation for further post-processing using DtiStudio, DiffeoMap and RoiEditor software (available at www.MriStudio.org). After correcting for eddy currents trace of diffusion, and motion artifacts, the following maps were generated: fractional anisotropy, vector, colorcoded fractional anisotropy, trace of diffusion, and axial and radial diffusivity. After rigid transformation for adjustment of position and rotation of images, regions of interest (ROI) were drawn manually, centered within the bilateral pontine corticospinal tract (CST), medial lemniscus, and middle cerebellar peduncle (MCP) (Fig. 1a–b and d–e). For the identification of each structure, color-coded fractional anisotropy maps were used in comparison to the MRI atlas by Oishi et al.10 Each ROI was drawn as large as possible on the axial plane while care was given not to include CSF along the margin of the structure on color-coded images. An additional ROI was drawn at the level of the lower brainstem covering the entire lower brainstem on the axial plane (Fig. 1c, f). For each analyzed structure, three different ROIs on contiguous magnetic resonance slices were placed and the average fractional anisotropy, mean, axial, and radial diffusivity values were calculated. The same post-processing was performed twice by the first author (with an interval of 4wks between both evaluations) and once by the second author in order to assess the intra- and interrater reliability of image analysis. Statistical analysis Generalized linear mixed effects models were used to evaluate the intra- and interrater perspectives and intraclass correlation coefficients (ICCs) were calculated. To evaluate the interrater reliability, the first evaluation by the first author was used. Intra- and interrater reliability were considered as good if the ICC was 0.7 or greater. Region and DTI parameters with an ICC of
ORIGINAL ARTICLE
Diffusion tensor imaging in pediatric Chiari type I malformation TADESSE ESHETU 1
| AVNER MEODED 2 | GEORGE I JALLO3 | BENJAMIN S CARSON 3 | THIERRY AGM HUISMAN 2 | ANDREA PORETTI 2 1 Division of Neuroradiology, The Russell H Morgan Department of Radiology and Radiological Science, The Johns Hopkins School of Medicine, Baltimore, MD; 2 Section of Pediatric Neuroradiology, Division of Pediatric Radiology, The Russell H Morgan Department of Radiology and Radiological Science, The Johns Hopkins School of Medicine, Baltimore, MD; 3 Division of Pediatric Neurosurgery, The Johns Hopkins School of Medicine, Baltimore, MD, USA. Correspondence to Andrea Poretti, Section of Pediatric Neuroradiology, Division of Pediatric Radiology, The Russell H Morgan Department of Radiology and Radiological Science, The Johns Hopkins School of Medicine, Charlotte R Bloomberg Children’s Center, Sheikh Zayed Tower, Room 4174, 1800 Orleans Street, Baltimore, MD 21287-0842, USA. E-mail: [email protected]
PUBLICATION DATA
Accepted for publication 27th March 2014. Published online ABBREVIATIONS
C1M CST DTI MCP ROI
Chiari type I malformation Corticospinal tract Diffusion tensor imaging Middle cerebellar peduncle Regions of interest
AIM Chiari type I malformation (C1M) may be symptomatic or asymptomatic as an incidental finding. In this retrospective study, we applied diffusion tensor imaging (DTI) to study the brainstem and cerebellar white matter tracts in C1M. METHOD Diffusion tensor imaging (DTI) data were acquired on a 1.5T MR-scanner using balanced pairs of diffusion gradients along 20 non-collinear directions. Measurements from regions of interest in each pontine corticospinal tract, medial leminscus, and middle cerebellar peduncle (MCP) and in the lower brainstem were obtained for fractional anisotropy and mean, axial, and radial diffusivity. Values in symptomatic and asymptomatic children, and children with and without hydromyelia were compared using analysis of variance. RESULTS Fifteen children with C1M (10 males, five females; six symptomatic [four with hydromyelia] and nine asymptomatic) were included. Median age was 6 years 5 months (range 2y 10mo–15y 4mo). No significant differences in DTI scalars were found in the lower brainstem. In both MCPs, axial diffusivity values were lower in symptomatic than in asymptomatic children (p=0.049 and p=0.035 respectively) and higher in children with hydromyelia versus without hydromyelia (p=0.018 and p=0.006 respectively). In the left MCP, mean diffusivity values were lower in symptomatic than in asymptomatic children (p=0.047). INTERPRETATION Our results show that microstructural tissue alterations may be present in C1M. Additionally, our study suggests a specific role for the MCPs in C1M. Further largescale studies are warranted.
INTRODUCTION Chiari I malformation (C1M) is a hindbrain abnormality characterized by ectopia/herniation of at least one cerebellar tonsil 5mm or more below the foramen magnum.1,2 The cerebellar tonsils are usually pointed or ‘peg shaped’. Associated neuroimaging findings may include a small posterior fossa, stretching of the fourth ventricle, shallow retrocerebellar cerebrospinal fluid (CSF) space, hydrocephalus, hydrosyringomyelia, cervico-medullary kinking, and bony deformities of the craniocervical junction.1,2 Children with C1M may present with a variety of neurological symptoms including occipital headaches exacerbated by Valsalva or sudden postural change, neck pain, visual disturbance, vertigo, and dizziness.1,3 However, with the progressing availability of diagnostic magnetic resonance imaging (MRI), children with asymptomatic C1M have increasingly been identified. Their diagnoses are typically made as an incidental finding on brain MRI studies obtained for various unrelated indications.3,4 © 2014 Mac Keith Press
Diffusion tensor imaging (DTI) is an advanced magnetic resonance technique that allows the study of the internal neuroarchitecture in vivo by measuring the three-dimensional shape and direction of diffusion in the brain.5 DTI is based on the directional movement of water, which is determined by the brain microstructure and imaged with diffusion-sensitive MRI sequences to generate virtual, threedimensional representations of the white matter fiber tracts. The diffusion tensor is a mathematical description of the magnitude and directionality (anisotropy) of the movement of water molecules in three-dimensional space. By measuring the complete tensor of the diffusion, various DTI parameters including the degree of anisotropic diffusion can be calculated. Decreased fractional anisotropy values in white matter tracts reflect injury with disorganized or disrupted myelin sheaths.6 Diffusion tensor imaging is, therefore, a suitable magnetic resonance tool to evaluate qualitatively and measure quantitatively the microscopic integrity of white matter structures within the brain tissue DOI: 10.1111/dmcn.12494 1
in congenital and acquired disorders of the pediatric brain.6,7 The aim of this study was to investigate the integrity of brainstem and cerebellar white matter tracts using DTI in children with C1M confirmed by anatomical MRI. We hypothesized decreased integrity/chronic injury of the white matter tracts in the lower brainstem in symptomatic compared to asymptomatic children, and in children with hydromyelia compared to children without hydromyelia.
METHOD This retrospective study was approved by the institutional research ethics board of The Johns Hopkins School of Medicine. Participants The inclusion criteria for this study were (1) confirmed diagnosis of C1M (herniation/ectopia of at least one cerebellar tonsil 5mm or more below the line drawn from the basion to the opisthion); (2) no association with other disorders such as Klippel-Feil or Costello syndrome;8 (3) for the children who underwent decompressive surgery, availability of presurgical DTI data without artifacts enabling a high quality DTI post-processing; and (4) age 18 years or younger at MRI diagnoses. Eligible patients were recruited through an electronic search of our pediatric neuroradiology database covering the period between 1 September 2010 and 31 March 2012. Review of the clinical charts provided detailed information about neurological features of the children. The symptomatic stage was defined according to Tubbs et al.1 and Aiken et al.9 Hydromyelia was defined as a dilatation of the central canal. The presence or absence of hydromyelia was assessed on axial and sagittal T1- and T2-weighted images of the spine. Diffusion tensor imaging All MRI studies were performed on a 1.5T scanner (Siemens Avanto, Erlangen, Germany) using our standard departmental protocol including 3D-T1- and axial T2-weighted images, an axial fluid attenuation inversion recovery sequence as well as a single shot spin echo, echo planar axial DTI sequence with diffusion gradients along 20 non-collinear directions. An effective high b-value of 1000s/mm2 was used for each of the 20 diffusion-encoding directions. We performed an additional measurement without diffusion weighting (b = 0s/ mm2). For the acquisition of the DTI data the following parameters were applied: repetition time (TR) = 7100ms; echo time (TE) = 84ms; slice thickness = 2.5mm, field-ofview (FOV) = 240 9 240mm and matrix size = 192 9 192. Parallel imaging iPAT = 2 with generalized auto-calibrating partial parallel acquisition reconstruction was used. The acquisition was repeated twice to enhance the signal-to-noise ratio. Additional axial and sagittal T1- and T2-weighted images of the spine were acquired according to our standard departmental protocol. 2 Developmental Medicine & Child Neurology 2014
•
What this paper adds Significant differences in axial diffusivity of the middle cerebellar peduncles were found in children with symptomatic versus asymptomatic Chiari type I malformation (C1M) as well as children with CIM with and without hydromyelia.
Image analysis Diffusion tensor imaging data of the children were transferred to an offline workstation for further post-processing using DtiStudio, DiffeoMap and RoiEditor software (available at www.MriStudio.org). After correcting for eddy currents trace of diffusion, and motion artifacts, the following maps were generated: fractional anisotropy, vector, colorcoded fractional anisotropy, trace of diffusion, and axial and radial diffusivity. After rigid transformation for adjustment of position and rotation of images, regions of interest (ROI) were drawn manually, centered within the bilateral pontine corticospinal tract (CST), medial lemniscus, and middle cerebellar peduncle (MCP) (Fig. 1a–b and d–e). For the identification of each structure, color-coded fractional anisotropy maps were used in comparison to the MRI atlas by Oishi et al.10 Each ROI was drawn as large as possible on the axial plane while care was given not to include CSF along the margin of the structure on color-coded images. An additional ROI was drawn at the level of the lower brainstem covering the entire lower brainstem on the axial plane (Fig. 1c, f). For each analyzed structure, three different ROIs on contiguous magnetic resonance slices were placed and the average fractional anisotropy, mean, axial, and radial diffusivity values were calculated. The same post-processing was performed twice by the first author (with an interval of 4wks between both evaluations) and once by the second author in order to assess the intra- and interrater reliability of image analysis. Statistical analysis Generalized linear mixed effects models were used to evaluate the intra- and interrater perspectives and intraclass correlation coefficients (ICCs) were calculated. To evaluate the interrater reliability, the first evaluation by the first author was used. Intra- and interrater reliability were considered as good if the ICC was 0.7 or greater. Region and DTI parameters with an ICC of
