Brain Iron and Neurotransmitter Analysis for PFAS-Linked Psychosis Risk by 3D UTE MRI and 1H-MRS
Poster No:
2632
Submission Type:
Abstract Submission
Authors:
Zhen Jiang1, Xin Shen2, Lisa Brown3, Liz Lee4, Humberto Monsivais1, Zoe Kourtzi4, Jason Cannon1, Daniel Foti3, Alexandra Lipka1,5,6, Uzay Emir1,7
Institutions:
1School of Health Science, College of Health and Human Sciences, Purdue University, West Lafayette, IN, 2Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, 3Department of Psychological Sciences, Purdue University, West Lafayette, IN, 4University of Cambridge, Cambridge, United Kingdom, 5College of Engineering, Purdue University, West Lafayette, IN, 6High Field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria, 7Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN
First Author:
Zhen Jiang
School of Health Science, College of Health and Human Sciences, Purdue University
West Lafayette, IN
School of Health Science, College of Health and Human Sciences, Purdue University
West Lafayette, IN
Co-Author(s):
Humberto Monsivais, Dr
School of Health Science, College of Health and Human Sciences, Purdue University
West Lafayette, IN
School of Health Science, College of Health and Human Sciences, Purdue University
West Lafayette, IN
Jason Cannon
School of Health Science, College of Health and Human Sciences, Purdue University
West Lafayette, IN
School of Health Science, College of Health and Human Sciences, Purdue University
West Lafayette, IN
Alexandra Lipka
School of Health Science, College of Health and Human Sciences, Purdue University|College of Engineering, Purdue University|High Field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna
West Lafayette, IN|West Lafayette, IN|Vienna, Austria
School of Health Science, College of Health and Human Sciences, Purdue University|College of Engineering, Purdue University|High Field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna
West Lafayette, IN|West Lafayette, IN|Vienna, Austria
Uzay Emir
School of Health Science, College of Health and Human Sciences, Purdue University|Weldon School of Biomedical Engineering, Purdue University
West Lafayette, IN|West Lafayette, IN
School of Health Science, College of Health and Human Sciences, Purdue University|Weldon School of Biomedical Engineering, Purdue University
West Lafayette, IN|West Lafayette, IN
Introduction:
Perturbations in excitatory and inhibitory neurotransmitters have been studied in disorders with psychotic features (Nakahara et al. 2022). The potential association between brain iron concentration and neurotransmitters (Unger et al. 2009) provides an opportunity to investigate the connection between PFAS exposure and risk for psychosis. This study postulates the developmental PFAS exposure as a potential environmental risk factor, that may trigger the presence of psychotic symptoms. To test this hypothesis, we analyzed potential correlations between brain iron concentration and Glutamate (Glu) levels, GABA levels, Glu/GABA ratio. 3D high-resolution UTE MRI was used for brain iron mapping. Metabolite levels of brain neurotransmitters in individuals were measured using 1H-MRS.
Methods:
The study population included 15 individuals aged 19 to 30, classified into healthy and psychotic groups (undisclosed). All the subjects were scanned using a whole-body 3T MRI system (Siemens Healthineers, Erlangen, Germany) with a vendor-supplied 20-channel receiver head coil. A 3D high-resolution rosette UTE sequence was used for all scans, detailed in (Shen et al. 2023). Image reconstruction was performed in MATLAB (MathWorks, USA) with ESPIRiT calibration and non-uniform fast Fourier transform in BART (Berkeley Advanced Reconstruction Toolbox). All images were co-registered to a standard template (MNI-152), in addition to brain tissue extraction via BET (Smith 2002) and bias field correction via AFNI and SPM12. The brain iron map was calculated by the fitting model from (Shen et al. 2023): C_iron=-1/0.1078∙log((1157-S_iron)/404.4). Where C_iron represents the iron concentration in the unit of mM, S_iron is signal intensity in the processed brain image. The Brainnetome masks were then applied to compute the iron concentration in regions of interest (ROIs). The 1H-MRS data was measured by semi-adiabatic localization using an adiabatic selective refocusing (semi-LASER) sequence (TE = 32 ms; TR = 3.5 s; 32 averages; Deelchand et al. 2015) and variable power RF pulses with optimized relaxation delays (VAPOR), water suppression, and outer volume saturation. Unsuppressed water spectra acquired from the same volume of interest were used to remove residual eddy current effects and to reconstruct the phased array spectra with MRspa. Two voxels of interest were manually centered in the posterior cingulate (8 mL) and the hippocampus (3.36 mL) based on the individual's T1-weighted image. Absolute and relative concentrations of GABA and Glu were acquired. A total of 246 ROIs underwent equal variances t-test to evaluate the differences of iron concentration between the two groups. Correlation analyses were then conducted between ROI iron concentration (p-value ≤ 0.05) and Glu, GABA, Glu/GABA ratio in corresponding subregions of the brain.
Results:
Significant differences in iron concentration without multiple comparisons were observed between the two groups (Table 1). Specifically, the iron concentration in PhG_L_6_6 showed a significant positive correlation with Glu levels (r = 0.54, p-value = 0.0377), as illustrated in Figure 1.
Conclusions:
Our results highlight significant iron concentration differences between individuals at high risk for psychosis and individuals without psychotic risk, suggesting iron as a potential psychosis biomarker. The positive correlation between iron concentration and Glu levels suggests neurodegenerative processes (Ward et al. 2014) may occur with elevated glutamate in PhG. Furthermore, UTE MRI demonstrated clinical potential in psychotic disorders. Future studies will include additional individuals, multiple comparisons. Multivariate analysis will be performed to mitigate unrelated factors (e.g. age, gender). Further investigation into the relationship between PFAS and risk for psychosis will include gathering individuals' PFAS concentrations from blood samples and correlating them with brain iron concentration, GABA, Glu, Glu/GABA ratio.
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia)
Novel Imaging Acquisition Methods:
Imaging Methods Other 2
Physiology, Metabolism and Neurotransmission :
Physiology, Metabolism and Neurotransmission Other 1
Keywords:
GABA
Glutamate
MR SPECTROSCOPY
MRI
Neurotransmitter
Psychiatric
Other - Brain Iron Map
1|2Indicates the priority used for review
Provide references using author date format
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