Cerebral Microvascular Reactivity and Neurocognition in Childhood Cancer Survivors

Abstract

PURPOSE: To determine the differences in cerebral microvascular reactivity (CVR) and neurocognition between childhood cancer survivors (CCS) and matched controls (CON). METHODS: Seven cancer survivors and seven matched [age, sex, and body mass index (BMI)]; healthy cancer-free controls were enrolled in the study. Each participant completed neurocognitive testing (i.e., IQ screening, memory, attention/executive, and fine motor) and a self-report survey of executive/self-regulation skills. A computer-controlled gas-blending device was used to evaluate baseline and manipulate end-tidal carbon dioxide (PetCO2). To alter brain blood flow, a PetCO2 gas challenge consisting of two square wave increases of 10 mmHg above baseline PetCO2 and a ramp protocol that decreased PetCO2 to 32 mmHg and then increased linearly to 50 mmHg over 7 mins was utilized. PetO2 was maintained at 100 mmHg. Each participant underwent brain imaging using a 3T MRI for structural and functional (BOLD) imaging. CVR (%BOLD signal change/mmHg CO2) was computed by using the robust linear least squares fit to the correlation between the two time courses. RESULTS: By design, CCS and CON were similar in age (27.1±1.1 vs. 26.0±0.8 y) and BMI (25.2±1.2 vs. 25.2±0.7 kg/m2) (all p>0.05). Baseline Pet CO2 (37.0±1.1 vs. 38.0±0.9 mmHg, p=0.34) was not significantly different between the two groups. Whole brain gray matter CVR was also not significantly different in CCS vs. CON groups for the full sequence (0.36±0.01 vs. 0.35±0.02 %BOLD/mmHg), squares waves only (0.37±0.02 vs. 0.36±0.02 %BOLD/mmHg) and ramp only (0.35±0.01 vs. 0.34±0.01 %BOLD/mmHg) (all p>0.05). The CVR variability (dCVR) was increased and model fit (R2) was significantly decreased in CCS compared with CON (p=0.004 and p=0.01, respectively) in the full sequence, but not in the square or ramp waveforms independently. No significant between-group differences were observed in neurocognitive testing. CONCLUSIONS: The data from this study suggest that childhood cancer survivors may have long-term treatment effects on microcirculation of the brain that affect CVR stability. Although this decline in brain microcirculation did not result in neurocognitive deficits, the long-term consequences of this decline in brain microvascular function have yet to be determined.