Longitudinal assessment of chemotherapy-induced brain connectivity changes in cerebral white matter and its correlation with cognitive functioning using the GQI

Vincent Chin-Hung Chen; Wei Chuang; Yuan-Hsiung Tsai; Roger S McIntyre; Jun-Cheng Weng

doi:10.3389/fneur.2024.1332984

Longitudinal assessment of chemotherapy-induced brain connectivity changes in cerebral white matter and its correlation with cognitive functioning using the GQI

Front Neurol. 2024 Feb 7:15:1332984. doi: 10.3389/fneur.2024.1332984. eCollection 2024.

Authors

Vincent Chin-Hung Chen^{1

2}, Wei Chuang³, Yuan-Hsiung Tsai^{1

4}, Roger S McIntyre^{5

6

7}, Jun-Cheng Weng^{2

3}

Affiliations

¹ School of Medicine, Chang Gung University, Taoyuan, Taiwan.
² Department of Psychiatry, Chang Gung Memorial Hospital, Chiayi, Taiwan.
³ Department of Medical Imaging and Radiological Sciences, and Department of Artificial Intelligence, Chang Gung University, Taoyuan, Taiwan.
⁴ Department of Diagnostic Radiology, Chang Gung Memorial Hospital, Chiayi, Taiwan.
⁵ Mood Disorder Psychopharmacology Unit, University Health Network, Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
⁶ Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
⁷ Departments of Psychiatry and Pharmacology, University of Toronto, Toronto, ON, Canada.

Abstract

Objective: Breast cancer was the most prevalent type of cancer and had the highest incidence rate among women worldwide. The wide use of adjuvant chemotherapy might have a detrimental effect on the human brain and result in chemotherapy-related cognitive impairment (CICI) among breast cancer patients. Furthermore, prior to chemotherapy, patients reported cancer-related cognitive impairment (CRCI), which might be due to physiological factors or mood symptoms. The present longitudinal study aimed to investigate microstructural and macroscale white matter alterations by generalized q-sampling imaging (GQI).

Methods: The participants were categorized into a pre-chemotherapy group (BB) if they were diagnosed with primary breast cancer and an age-matched noncancer control group (HC). Some participants returned for follow-up assessment. In the present follow up study, 28 matched pairs of BB/BBF (follow up after chemotherapy) individuals and 28 matched pairs of HC/HCF (follow up) individuals were included. We then used GQI and graph theoretical analysis (GTA) to detect microstructural alterations in the whole brain. In addition, we evaluated the relationship between longitudinal changes in GQI indices and neuropsychological tests as well as psychiatric comorbidity.

Findings: The results showed that disruption of white matter integrity occurred in the default mode network (DMN) of patients after chemotherapy, such as in the corpus callosum (CC) and middle frontal gyrus (MFG). Furthermore, weaker connections between brain regions and lower segregation ability were observed in the post-chemotherapy group. Significant correlations were observed between neuropsychological tests and white matter tracts of the CC, MFG, posterior limb of the internal capsule (PLIC) and superior longitudinal fasciculus (SLF).

Conclusion: The results provided evidence of white matter alterations in breast cancer patients, and they may serve as potential imaging markers of cognitive changes. In the future, the study may be beneficial to create and evaluate strategies designed to maintain or improve cognitive function in breast cancer patients undergoing chemotherapy.

Keywords: breast cancer; chemotherapy; cognitive function; generalized q-sampling imaging (GQI); longitudinal study.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by research grants MOST107-2221-E-182-054-MY3 and NSTC112-2221-E-182-013-MY3 from the National Science and Technology Council, Taipei, Taiwan, respectively. This study was also supported by grants NMRPD1H0101~3 from Chang Gung University, Taoyuan, Taiwan and CORPG6G0101~3 and CORPG6G0121~3 from Chang Gung Memorial Hospital, Chiayi, Taiwan. The funders of the study had no role in the study design, data collection, data analysis, data interpretation, or writing of the report.