Peripheral Inflammation and White Matter Changes in Breast Cancer: A Fixel-Based Diffusion MRI Study
Poster No:
193
Submission Type:
Abstract Submission
Authors:
Rob Colaes1, Gwen Schroyen1, Ahmed Radwan1, Rebeca Alejandra Gavrila Laic1, Sigrid Hatse1, Ann Smeets1, Karen Caeyenberghs2, Stefan Sunaert1, Sabine Deprez1
Institutions:
1KU Leuven, Leuven, Vlaams-Brabant, 2Deakin University, Burwood, Victoria
First Author:
Co-Author(s):
Introduction:
Chemotherapy-induced cognitive impairment's pathophysiology remains unclear. Besides direct neurotoxicity, chemotherapy may trigger peripheral pro-inflammatory responses leading to neuroinflammation and neuronal injury. In this longitudinal study, we assessed changes in pro-inflammatory markers and fixel-based diffusion MRI measures before and after chemotherapy in patients with breast cancer.
Methods:
This longitudinal study included 32 patients receiving chemotherapy for breast cancer (C+), 35 chemotherapy-naïve patients (C-) and 46 healthy women (HC) age- and education matched. Participants were assessed at diagnosis (T0), three months- (T1) and 1-year post-chemotherapy (T2), or at matched intervals. Data collection included multi-shell diffusion-weighted images (voxel=2x2x2mm, TE/TR=85/6400ms, FA=90°, FOV=112x112x66, b=0/200/500/1200/2400/4000, directions=11/20/20/30/61/61, multiband=3), and serum neuroinflammatory markers VILIP-1, MCP-1, sTREM-1, sTREM-2, BDNF, VEG-F, IL-6, IL-18, TNF-ɑ, sRAGE, CX3CL1 and NfL were derived. Image preprocessing was performed using an MRtrix3-based pipeline (Tournier et al., 2019). Multi-tissue constrained spherical deconvolution was used to construct fiber oriented distributions (FOD). A population-based FOD template was constructed, and subject-specific FODs were segmented to estimate fixels and their fiber density (Smith et al., 2013) (Raffelt et al., 2012). Fiber density (FD), fiber cross-section (log-FC), and a combined measure (FDC) were calculated. Linear mixed-effects models were fitted to compare group-differences in each marker over time with HC and T0 as references, including age at T0 as a covariate. Significance was assessed at FDR corrected p<0.05. Group differences in fixel measures were assessed at baseline, T1-T0, and T2-T0 (Genc et al., 2018). Statistical inference was performed using connectivity-based fixel enhancement (Raffelt et al., 2015), with age and intracranial volume as covariates (Smith et al., 2019). Significance was assessed at a FWER corrected p<0.05. Individual linear regression models explored associations between changes in serum markers and fixel measures in regions with significant decreases, reflecting reduced white matter integrity. Significance was assessed at uncorrected p<0.05.
Results:
At T1, C+ patients exhibited significant changes in NfL, BDNF, IL-6, sTREM-1, IL-18, TNF-α, sRAGE, and CX3CL1. At T2, significant changes were observed in NfL, sTREM-1, and CX3CL1 in C+ patients, while C- patients showed significant changes in BDNF, sTREM-1, and CX3CL1. Interaction effects were observed in log-FC in the right superior thalamic radiation and left middle longitudinal fasciculus, but within-group analysis showed no significant changes. In C+ patients, significant decreases at T1 were seen in FD (Nfixels=21, Figure 1A) and FDC (Nfixels=321, Figure 1B) in the left inferior longitudinal fasciculus (ILF), and at T2 in log-FC (Nfixels=68, Figure 1C) in the superior genu of the prefrontal corpus callosum (pfCC). A significant increase in log-FC (Nfixels=36) was observed at T2 in the left ILF. In C- patients, a significant decrease at T2 was found in log-FC (Nfixels=154, Figure 1D) in the posterior genu of the pfCC, and a significant increase in log-FC (Nfixels=64) in the left temporal cingulum. Regression models revealed that decreases between T1-T0 in IL-6, sTREM-1, CX3CL1, and sRAGE were associated with decreases between T2-T0 in log-FC within the pfCC.
Conclusions:
This longitudinal study explored peripheral inflammation as a mechanism in chemotherapy-induced white matter damage. After chemotherapy, C+ patients showed alterations in inflammatory markers and reduced white matter integrity in the left ILF and pfCC. Short-term inflammatory changes were linked to long-term microstructural alterations, suggesting that peripheral inflammation may contribute to chemotherapy-induced white matter damage.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 1
Modeling and Analysis Methods:
Diffusion MRI Modeling and Analysis 2
Keywords:
Blood
Cognition
MRI
Neurological
Toxins
Treatment
White Matter
WHITE MATTER IMAGING - DTI, HARDI, DSI, ETC
Other - Cancer
1|2Indicates the priority used for review
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Were any human subjects research approved by the relevant Institutional Review Board or ethics panel? NOTE: Any human subjects studies without IRB approval will be automatically rejected.
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Provide references using APA citation style.
Raffelt, D. A. (2015). Connectivity-based fixel enhancement: Whole-brain statistical analysis of diffusion MRI measures in the presence of crossing fibres. NeuroImage, 117, 40–55.
Raffelt, D. (2012). Apparent Fibre Density: a novel measure for the analysis of diffusion-weighted magnetic resonance images. NeuroImage, 59(4), 3976–3994.
Smith, R. (2019). On the regression of intracranial volume in Fixel-Based Analysis.
Smith, R. (2013). SIFT: Spherical-deconvolution informed filtering of tractograms. NeuroImage, 67, 298–312.
Tournier, J.-D. (2019). MRtrix3: A fast, flexible and open software framework for medical image processing and visualisation. NeuroImage, 202(116137), 116137.