To identify all sites within the brain where signal increases are seen on unenhanced T1-weighted images after a large number (35 or more) of linear GBCA administrations.PACS was searched for patients having >=35 GBCA enhanced examinations including a brain MRI before any GBCA administration and after the last GBCA administration. The period of search from 1/1/1999 to 3/30/2015 corresponded to use of gadopentetate dimeglumine, gadodiamide and most recently gadobenate dimeglumine as the primary GBCA for brain MRI. GBCA dose was 0.1mmol/kg body weight for scanning at 1.5 or 3T. For each patient, unenhanced T1-weighted images at baseline (prior to any GBCA), after 6, 12, 24 and the final GBCA administrations were reviewed by 3 radiologists (independently and blinided to all patient information) for areas of increased signal. Regions noted by all 3 radiologists to have increased signal intensity on unenhanced T1-weighted images were considered positive.16 patients were identified with 35 to 88 (mean=47) GBCA administrations. The ratio of male:female was 9:7 with an age range of 18 to 60 years. Primary indications for MRI included primary brain tumor (n=13), brain lymphoma (n=2), brain metastasis (n=1). The percent of patients showing elevated T1 signal on unenhanced images at baseline, after 6, 12, 24 and all GBCA injections is shown in Table 1. Elevated signal intensity on unenhanced T1-weighted images was found by all 3 radiologists after all GBCA administration (35 or more in every subject), in dentate nucleus (100%), globus pallidus (100%), cerebral peduncles (100%), substantial nigra (88%), red nucleus (88%), and colliculi (81%).Typical subjects showed as Fig1 and Fig2. The other dominant brain structures as thalamus also showed significant signal intensity elevation at posterior thalamus (positive rate from 0 after 6 GBCA administration to 94% at the final GBCA administration), and among these cases, whole thalamus became bright in 4 cases (25%). In the area of basil ganglia, internal capsule and caudate nucleus showed positively separately in 8 cases (50%) and 5 cases (33%) after final administration of GBCA. Other positive finding showed in rare cases, 2 (13%) cases in pons, 1 case(6%) in posterior part of brain stem(including posterior inferior part of pons and posterior medulla oblangata), 2 (13%) cases in anterior commissure, 1 case(6%) in pituitary gland, 1 case(6%) in mammillary body, and 1 case(6%) in putamen. Brain structures results showed as Table 1. None of the patients had any clinical sequelae attributed to the elevated brain signals on unenhanced T1-weighted images.Recent demonstration of increased signal in the dentate nucleus and globus pallidus following 6 to 12 linear GBCA administrations by Kanda et al [1-2] and confirmed by others [3-8]raises the possibility of residual gadolinium lingering in the brain. This has been confirmed by autopsy studies identifying gadolinium in these locations in amounts corresponding directly to the number of linear GBCA administrations [9-11]. These data in patients with a much larger number (>=35) of linear GBCA administrations demonstrate additional regions of the brain which eventually have elevated signal on T1-weighted images. Although some of these changes may reflect aging or treatments these patients received, it raises the possibility that trace amounts of GBCA or dissociated Gd3+ can accumulate in additional locations beyond dentate nucleus and globus pallidus. Since these findings are not associated with any known adverse effects in spite of hundreds of millions of linear GBCA administrations worldwide, there does not appear to be any clinical significance.