Purpose To explore the extent of signal hyperintensity in the brain on unenhanced T1-weighted magnetic resonance (MR) images with increasing gadolinium-based contrast agent (GBCA) doses in patients who received 35 or more linear GBCA administrations. Materials and Methods In this institutional review board-approved HIPAA-compliant retrospective study, picture archiving and communication systems of two tertiary referral hospitals were searched to identify patients who received 35 or more linear GBCA administrations. Unenhanced T1-weighted images of the brain in patients after six, 12, and 24 GBCA administrations and after the final GBCA administration were independently reviewed by three radiologists to identify sites where T1 signal intensity was increasing. Areas identified by all three observers as increasing in T1 signal intensity when compared with baseline images were further analyzed with a quantitative region of interest analysis measuring the rate of signal increase per injection and the total change after 24 linear GBCA administrations relative to reference tissues that did not show T1 shortening. Results Qualitative analysis of 13 patients with 39-59 linear GBCA administrations showed visually detectable T1 shortening in the dentate nucleus (n = 13), globus pallidus (n = 13), substantia nigra (n = 13), posterior thalamus (n = 12), red nucleus (n = 10), colliculi (n = 10), superior cerebellar peduncle (n = 7), caudate nucleus (n = 4), whole thalamus (n = 3), and putamen (n = 2). Quantitative analysis enable confirmation of signal intensity increases on unenhanced T1-weighted images relative to reference tissues in the dentate nucleus (0.53% signal intensity increase per injection, P < .001), globus pallidus (0.23% increase, P = .009), posterior thalamus (0.26% increase, P < .001), substantia nigra (0.25% increase, P = .01), red nucleus (0.25% increase, P = .01), cerebellar peduncle (0.19% increase, P = .001), and colliculi (0.21% increase, P = .02). Conclusion Increased signal intensity on unenhanced T1-weighted images was seen in the posterior thalamus, substantia nigra, red nucleus, cerebellar peduncle, colliculi, dentate nucleus, and globus pallidus. © RSNA, 2016.