Abstract
IntroductionDiffusion tensor imaging (DTI) assumes a single pool of anisotropically diffusing water to calculate fractional anisotropy (FA) and is commonly used to ascertain white matter (WM) deficits in schizophrenia. At higher b-values, diffusion-signal decay becomes bi-exponential, suggesting the presence of two, unrestricted and restricted, water pools. Theoretical work suggests that semi-permeable cellular membrane rather than the presence of two physical compartments is the cause. The permeability–diffusivity (PD) parameters measured from bi-exponential modeling may offer advantages, over traditional DTI-FA, in identifying WM deficits in schizophrenia.MethodsImaging was performed in N = 26/26 patients/controls (age = 20–61 years, average age = 40.5 ± 12.6). Imaging consisted of fifteen b-shells: b = 250–3800 s/mm2 with 30 directions/shell, covering seven slices of mid-sagittal corpus callosum (CC) at 1.7 × 1.7 × 4.6 mm. 64-direction DTI was also collected. Permeability–diffusivity-index (PDI), the ratio of restricted to unrestricted apparent diffusion coefficients, and the fraction of unrestricted compartment (Mu) were calculated for CC and cingulate gray matter (GM). FA values for CC were calculated using tract-based-spatial-statistics.ResultsPatients had significantly reduced PDI in CC (p ≅ 10− 4) and cingulate GM (p = 0.002), while differences in CC FA were modest (p ≅ .03). There was no group-related difference in Mu. Additional theoretical-modeling analysis suggested that reduced PDI in patients may be caused by reduced cross-membrane water molecule exchanges.ConclusionPDI measurements for cerebral WM and GM yielded more robust patient–control differences than DTI-FA. Theoretical work offers an explanation that patient–control PDI differences should implicate abnormal active membrane permeability. This would implicate abnormal activities in ion-channels that use water as substrate for ion exchange, in cerebral tissues of schizophrenia patients.
Highlights
Diffusion tensor imaging (DTI) assumes a single pool of anisotropically diffusing water to calculate fractional anisotropy (FA) and is commonly used to ascertain white matter (WM) deficits in schizophrenia
The PD-modeling can be applied to gray matter (GM), where diffusion decay is bi-exponential (Clark et al, 2002). We explored this by fitting PD-model to data collected from the cingulate cortex overlaying the corpus callosum, and examined the group-differences in GM-based Permeability– diffusivity-index (PDI) between schizophrenia and healthy control
The effect sizes on group difference of PDI at the genu (Cohen's d = 1.14) was about twice that of the FA at the genu (d = 0.52), suggesting that PDI and FA both identified white matter abnormalities in schizophrenia while PDI more than doubled the effect size in differentiating the two groups
Summary
Diffusion tensor imaging (DTI) assumes a single pool of anisotropically diffusing water to calculate fractional anisotropy (FA) and is commonly used to ascertain white matter (WM) deficits in schizophrenia. Theoretical work offers an explanation that patient–control PDI differences should implicate abnormal active membrane permeability This would implicate abnormal activities in ion-channels that use water as substrate for ion exchange, in cerebral tissues of schizophrenia patients. DTI uses a single diffusion weighting b-value and the 3D, multivariate Gaussian model to quantify diffusion behavior of water (Basser and Pierpaoli, 1996) It assumes a single pool of anisotropically diffusing water and uses a mono-exponential function to describe the signal decay due to diffusion weighting.
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