Early white matter injuries associated with dopamine transporter dysfunction in patients with acute CO intoxication: A diffusion kurtosis imaging and Tc-99m TRODAT-1 SPECT study
Patients with CO intoxication were demonstrated to exhibit white matter (WM) injuries, changes in substantia nigra, dopamine transporter dysfunctions of striatum and Parkinsonism symptoms. We aimed to investigate the relationship between WM injuries of dopaminergic pathways and dopamine transporter dysfunctions of the striatum in patients with acute CO intoxication using both diffusion kurtosis imaging (DKI) and single photon-emission computed tomography (SPECT).
Materials and methods
Seventeen patients with acute CO intoxication and 19 age- and gender-matched healthy subjects were enrolled. DKI data were acquired from all participants and Tc-99m-TRODAT-1 SPECT scan was performed on each patient. DKI datasets were fitted to obtain axial, radial and mean diffusivity, fractional anisotropy, axial, radial and mean kurtosis for voxel-based comparison. In addition, the TRODAT-1 binding ratio of the striatum was calculated using the occipital cortices as a reference. In significant regions, correlational analysis was performed to understand the relationship between DKI indices and TRODAT-1 binding ratio.
The results showed that DKI indices were significantly altered in multiple WM regions broadly involving the basal ganglia-thalamocortical circuit and nigrostriatal pathway. The correlation analysis further revealed significant correlations between DKI indices and the TRODAT-1 binding ratio in the nigrostriatal pathway (absolute correlation coefficients ranged from 0.5992 to 0.6950, p<0.05), suggesting that CO-induced early WM injuries were associated with dopamine transporter dysfunctions of striatum.
We concluded that DKI and Tc-99m-TRODAT-1 SPECT scans were helpful in early detection of global WM injuries associated with dysfunctions of dopamine transporter in patients with acute CO intoxication.
• Voxel-based diffusion kurtosis imaging analysis was helpful in globally detecting early white matter injuries in patients with acute CO intoxication.
• CO-induced early white matter injuries were broadly located in basal ganglia-thalamocortical circuit and nigrostriatal pathway.
• Early white matter injuries in dopaminergic pathways were significantly correlated with dopamine transporter dysfunctions of the striatum.
KeywordsDiffusion magnetic resonance imaging Carbon monoxide Dopamine transporter
Anterior corona radiata
Brain extraction tool
Diffusion kurtosis estimator
Diffusion kurtosis imaging
Diffusion tensor imaging
FMRIB software library
Genu of corpus callosum
Hyperbaric oxygen therapy
Inferior longitudinal fasciculus
Middle cerebellar peduncle
Posterior corona radiata
Posterior limb of internal capsule
Splenium of corpus callosum
Superior corona radiata
Superior longitudinal fasciculus
Single photon emission computed tomography
- SPM 8
Statistical Parametric Mapping version 8
Duration of coma
Time after onset
This study received funding by Dr. Ping-Hong Lai and Dr. Ming-Chung Chou from Ministry of Science and Technology (MOST) of Taiwan (106-2314-B-075B-002 -MY3 and 101-2314-B-037-047-MY2) and Dr. Jie‐Yuan Li from Veterans General Hospitals and University System of Taiwan Joint Research Program (VGHUST100‐G3‐2‐3).
Compliance with ethical standards
The scientific guarantor of this publication is Dr. Jie-Yuan Li.
Conflict of interest
The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article.
Statistics and biometry
No complex statistical methods were necessary for this paper.
Written informed consent was obtained from all subjects (patients) in this study.
Institutional Review Board approval was obtained.
• Case-control study
• Performed at one institution
- 4.Chiew AL, Buckley NA (2014) Carbon monoxide poisoning in the 21st century. Crit Care (2014) 18:221Google Scholar
- 11.Tsai PH, Chou MC, Chiang SW et al (2017) Early white matter injuries in patients with acute carbon monoxide intoxication A tract-specific diffusion kurtosis imaging study and STROBE compliant article. Medicine (Baltimore) 96Google Scholar
- 12.Kinoshita T, Sugihara S, Matsusue E, Fujii S, Ametani M, Ogawa T (2005) Pallidoreticular damage in acute carbon monoxide poisoning: Diffusion-weighted MR imaging findings. AJNR Am J Neuroradiol 26:1845–1848Google Scholar
- 15.Huang WS, Lin SZ, Lin JC, Wey SP, Ting G, Liu RS (2001) Evaluation of early-stage Parkinson's disease with Tc-99m-TRODAT-1 imaging. J Nucl Med 42:1303–1308Google Scholar
- 20.Beppu T, Fujiwara S, Nishimoto H et al (2012) Fractional anisotropy in the centrum semiovale as a quantitative indicator of cerebral white matter damage in the subacute phase in patients with carbon monoxide poisoning: correlation with the concentration of myelin basic protein in cerebrospinal fluid. J Neurol 259:1698–1705CrossRefGoogle Scholar