Article Figures & Data
Figures
- Fig 1.
Images obtained in a 7.8-year-old girl with SCD show how image segmentation was performed.
A and B, T1-weighted (A) and T2-weighted (B) MR images obtained at the same section level.
C, Segmented image made by combining T1-weighted, T2- or proton density-weighted, and FLAIR images shows 16 types of tissue as nine different gray scale levels.
D, Segmented and classified image shows gray matter (yellow), white matter (green), blood vessels and membranes (dark blue), and CSF (light blue). To calculate central gray matter (basal ganglia) volume separate from cortical volume, all tissues external to the basal ganglia were erased. The cortical gray matter volume was then calculated as a function of total gray matter volume minus central gray matter volume.
- Fig 2.
Scatterplot shows volume of all tissues in patients with SCD and in healthy control children.
- Fig 3.
Scatterpolots show cortical gray matter volume (top) and white matter volume (bottom) in patients with SCD and in healthy control children.
Tables
- TABLE 1:
Validation of the methods for measuring brain volume performed in five volunteers
Structure Volume (mL) Measured by 5-mm Thick Sections Volume (mL) Measured by 3-mm Thin Sections White matter 33.86 ± 3.33 34.00 ± 3.02 Gray matter 58.28 ± 3.77 58.44 ± 3.60 CSF 9.68 ± 3.26 9.54 ± 3.18 Note.—Data are mean ± SD. The mean difference between the two methods was 0.053 mL. A paired t test comparing 15 measurements made on thick sections to the same measurements made on thin sections was not significant (t statistic = 0.5524 with 14 degrees of freedom; P = .589).
- TABLE 2:
Comparison of descriptive data in patients with SCD and control subjects without controlling for age
Comparison Patients (n = 83)* Controls (n = 43)* % Difference P value† Subject age (y) 9.36 ± 3.83 10.02 ± 3.61 −6.40 NS Proportion male (%) 56.6 58.1 −2.60 NS Volume (mL) Total brain 94.72 ± 8.11 97.24 ± 6.10 −2.60 .04 White matter 27.16 ± 4.55 27.52 ± 4.59 −1.30 NS Gray matter 61.30 ± 6.10 63.99 ± 5.18 −4.20 .01 Central gray matter 10.60 ± 1.46 11.32 ± 1.51 −6.40 .01 Cortical gray matter 50.96 ± 4.37 52.58 ± 4.59 −3.10 .03 CSF 6.26 ± 2.55 5.73 ± 1.90 9.20 NS Note.—NS indicates not significant. Age did not differ significantly between patients and controls, so this approach may be valid.
* Data are mean ± SD.
† Statistical testing was performed with a two-sample t test.
- TABLE 3:
Least-squares means of brain volumes between the 83 patients with SCD and 43 control subjects as a function of age
Volume and Group 5.0 Years Old P Value 9.5 Years Old P Value 11.50 Years P Value Total brain Control 98.29 ± 1.94 .0127 97.35 ± 1.13 NS 96.93 ± 1.21 NS SCD 92.49 ± 1.22 94.79 ± 0.80 95.82 ± 0.92 White matter Control 26.63 ± 1.16 NS 27.43 ± 0.68 NS 27.79 ± 0.72 NS SCD 25.25 ± 0.72 27.22 ± 0.48 28.10 ± 0.55 Gray matter Control 67.47 ± 1.50 .0004 64.35 ± 0.87 .0052 62.96 ± 0.94 NS SCD 61.07 ± 0.94 61.30 ± 0.62 61.41 ± 0.71 Central gray matter Control 11.98 ± 0.38 .0014 11.39 ± 0.22 .0045 11.13 ± 0.24 NS SCD 10.51 ± 0.24 10.60 ± 0.16 10.64 ± 0.18 Cortical gray matter Control 55.54 ± 1.14 .0021 52.89 ± 0.67 .0195 51.71 ± 0.72 NS SCD 51.29 ± 0.72 50.95 ± 0.48 50.80 ± 0.54 CSF Control 4.18 ± 0.61 .0067 5.56 ± 0.36 NS 6.18 ± 0.38 NS SCD 6.17 ± 0.38 6.27 ± 0.26 6.31 ± 0.29 Note.—NS indicates not significant. Data are mean ± standard error.
- TABLE 4:
Age-related change in brain volume in 83 patients with SCD and 43 control subjects
Effect Estimate* Standard Error P Value† Total brain volume Intercept for controls 99.34 3.36 <.0001 Intercept for SCD 89.93 2.12 <.0001 Age × controls −0.21 0.32 NS Age × SCD patients 0.51 0.21 .0162 White matter Intercept for controls 25.74 2.00 <.0001 Intercept for SCD 23.06 1.27 <.0001 Age × controls 0.18 0.19 NS Age × SCD patients 0.44 0.13 .0007 Gray matter Intercept for controls 70.95 2.59 <.0001 Intercept for SCD 60.81 1.63 <.0001 Age × controls −0.69 0.24 .0050 Age × SCD patients 0.05 0.16 NS Central gray matter Intercept for controls 12.64 0.66 <.0001 Intercept for SCD 10.41 0.42 <.0001 Age × controls −0.13 0.06 .0360 Age × SCD patients 0.02 0.04 NS Cortical gray matter Intercept for controls 58.49 1.98 <.0001 Intercept for SCD 51.66 1.25 <.0001 Age × controls −0.59 0.19 .0019 Age × SCD patients −0.07 0.12 NS CSF Intercept for controls 2.65 1.05 .0130 Intercept for SCD 6.05 0.66 <.0001 Age × controls 0.31 0.10 .0024 Age × SCD patients 0.02 0.07 NS * Estimates of fitted model between groups.
† The P value for the “Intercept for controls” and the “Intercept for SCD” tests whether the respective intercept is significantly different from zero. The P value for “Age × controls” and “Age × SCD patients” tests whether there is a significant effect of age in controls and patients, respectively, by testing whether the slope is significantly different from zero slope.
- TABLE 5:
Least-squares means of brain volumes as a function of genotype in 70 patients with hemoglobin SS, 20 control subjects with hemoglobin AS, and 23 control subjects with hemoglobin AA
Volume and Genotype 5.0 Years Old 9.5 Years Old 11.5 Years Old Total brain Means ± SE AA 98.79 ± 2.50 97.51 ± 1.57 96.95 ± 1.66 AS 97.37 ± 3.28 97.12 ± 1.70 97.01 ± 1.87 SS 92.18 ± 1.34 94.59 ± 0.89 95.66 ± 1.00 P Value AA vs SS 0.0217 NS NS AS vs SS NS NS NS AA vs AS NS NS NS White matter Means ± SE AA 25.61 ± 1.47 26.53 ± 0.92 26.94 ± 0.98 AS 27.90 ± 1.93 28.48 ± 0.99 28.73 ± 1.10 SS 25.00 ± 0.79 26.96 ± 0.53 27.83 ± 0.59 P Value AA vs SS NS NS NS AS vs SS NS NS NS AA vs AS NS NS NS Gray matter Means ± SE AA 68.95 ± 1.95 65.55 ± 1.19 64.03 ± 1.26 AS 65.52 ± 2.49 62.95 ± 1.29 61.82 ± 1.40 SS 60.70 ± 1.02 61.17 ± 0.68 61.37 ± 0.77 P Value AA vs SS 0.0002 0.0018 NS AS vs SS NS NS NS AA vs AS NS NS NS Central gray matter Means ± SE AA 11.99 ± 0.49 11.37 ± 0.31 11.09 ± 0.32 AS 11.94 ± 0.64 11.41 ± 0.33 11.17 ± 0.37 SS 10.48 ± 0.26 10.61 ± 0.18 10.66 ± 0.20 P Value AA vs SS 0.0078 0.0340 NS AS vs SS 0.0374 0.0343 NS AA vs AS NS NS NS Cortical gray matter Means ± SE AA 56.96 ± 1.45 54.18 ± 0.91 52.94 ± 0.96 AS 53.80 ± 1.90 51.40 ± 0.98 50.33 ± 1.08 SS 51.07 ± 0.78 50.86 ± 0.52 50.77 ± 0.58 P Value AA vs SS 0.0005 0.0019 NS AS vs SS NS NS NS AA vs AS NS 0.0397 NS CSF Means ± SE AA 4.22 ± 0.77 5.44 ± 0.48 5.98 ± 0.51 AS 3.95 ± 1.00 5.70 ± 0.52 6.47 ± 0.58 SS 6.48 ± 0.41 6.46 ± 0.28 6.45 ± 0.31 P Value AA vs SS 0.0111 NS NS AS vs SS 0.0221 NS NS AA vs AS NS NS NS Note.—NS indicates not significant; SE, standard error.
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