Introduction: Children with acute lymphoblastic leukemia (ALL) require neurotoxic treatment during critical periods of brain development. Multispectral magnetic resonance imaging (MRI) offers opportunities to characterize the impact of chemotherapy on the developing brain, but this has been constrained by concerns regarding feasibility of obtaining quality MRIs from these critically ill children at a young age. Our goal is to demonstrate a framework for improving the feasibility of non-sedated, multispectral MRI in newly diagnosed ALL patients. Methods: Participants were enrolled from August 2023 through February 2026, and included newly diagnosed ALL patients and controls recruited from the community ages 3-10 years old. Participants completed non-sedated, non-enhanced-contrasted MRI on a 3T scanner, including anatomical T1-weighted and QALAS sequences for quantitative mapping, diffusion weighted MRI (DWI), MR Spectroscopy (MRS), and resting-state functional MRI (rs-fMRI). A sequence was considered complete if data quality was sufficient for successful image processing. Mixed-effects logistic regression models were used determine if group and study visit were associated with MRI success rates across sequences. Results: The sample included 17 ALL patients and 30 controls, who contributed to 38 and 75 observations, respectively. Of 113 attempted scans, 105 had ≥1 sequence completed (93%). Across assessments, ALL patients were less likely to complete a scan (31 of 38 attempts; raw rate: 82%) relative to controls (73 of 75; raw rate: 96%; model-estimated difference=-14.1%, 95%CI=-27.1%; -1.1%, p=0.033). Baseline success rate was 65% (11 of 17) for ALL patients and 93% (28 of 30) for controls (model-estimated difference=-26.8%, 95%CI=-52.7%; -0.9%, p=0.42); however, nearly all T1w scans in ALL patients were successful at follow-up visits (20 of 21; 95%), with no significant differences between groups (model-estimated difference at follow-up 1=-2.1%, 95%CI=-11.7%; 7.6%; model-estimated difference at follow-up 2=-8.3%, 95%CI=-26.3%; 9.6%). A similar pattern was observed for DWI, MRS and rs-fMRI sequences with relatively high completion rates at follow-up assessments. Discussion: Non-sedated multispectral MRI is feasible in young children with newly diagnosed ALL, particularly with repeated visits and structured behavioral preparation. These results highlight opportunities to capture the scope and depth of neurodevelopmental changes concurrent with ALL treatment.

The authors have declared no competing interest.

This work was funded by the National Cancer Institute.

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