Effect on Body Movement and Mental Skills in Patients Who Received Gadolinium-based Contrast Media for Magnetic Resonance Examination Multiple Times Within 5 Years

Inclusion Criteria:

• Participant must be neurologically normal, defined as free of unstable neurologicand psychiatric disease as confirmed by a normal neurologic examination at screening

• Participant (GBCA-exposed or controls) agrees to undergo unenhanced magneticresonance imaging (UE-MRI) of the brain at enrollment and at the end of theobservation period (5 years)

• Participants should have at least 1 of the following indications: a) Medium to highrisk for breast cancer or dense breasts undergoing breast cancer screening with MRI,b) Elevated prostate-specific antigen (PSA) and under active diagnostic surveillancefor prostate cancer, c) Chronic liver disease (eg, liver cirrhosis limited to Childclass A, post-hepatitis chronic hepatopathy, or primary sclerosing cholangitis) forsurveillance of hepatocellular carcinoma development, d) Low-grade colorectal canceror neuroendocrine tumor undergoing screening for liver metastases or e) Branch-ductintraductal papillary mucinous neoplasm (IPMN) of the pancreas (maximum size ≤2 cm)undergoing imaging surveillance.

In addition, for participants in the GBCA Arms only:

• Each participant should be likely to undergo ≥5 GBCA-enhanced MR examinations withthe same GBCA at least annually throughout the 5-year study duration

• Prospective participants with up to 3 well documented GBCA administrations prior tostudy screening are acceptable, provided that the imaging was performed with thesame GBCA as the one to be prospectively used in the study. If the GBCA used cannotbe identified, he/she cannot be enrolled.

For the Control Arm:

• Participants who never had and are not likely to receive any GBCA injection duringthe course of the study

• Each control participant must be willing to undergo UE-MRI of the brain at baselineand at Year 5. In Years 1 to 4, the control participants will undergo theirclinically indicated UE-MRIs, computed tomography (CT), ultrasound, or X-rayprocedures

Exclusion Criteria:

• As evidenced by history or determined in the neurologic exam at screening,concurrent neurological and/or psychiatric disease (or treatments) that couldinfluence the results of the study's motor and cognitive tests (e.g. Cerebrovasculardisease, Multiple sclerosis, Neurodegenerative disease, Malignant disease other thanlisted in indications, Carcinoid tumors, Epilepsy, Prior neurosurgery, Psychoticdisorders or any prior psychotic episode not otherwise specified - any documentedprior history of chronic schizophrenia, Remittent or current medically confirmedmajor depressive disorder or bipolar disorder, History of long-term major depressionor bipolar affective disorder with an active episode in the past 2 to 5 years,Neurodevelopmental disorders (eg, trisomy 21), Uncontrolled severe migraine,Uncontrolled or controlled anxiety or depression within 6 months before enrollment,Screening scores of ≤24 on the MMSE and/or ≥11 on the Hospital Anxiety andDepression Scale (HADS)).

• Prior, planned, or ongoing chemotherapy or brain irradiation

• Use of concomitant medication(s) affecting neuro-cognitive or motor function

• Substance or alcohol abuse as determined by the investigator

• Alcoholic cirrhosis

• Renal disease, defined as estimated glomerular filtration rate (eGFR) < 60mL/min/1.73 m2

• History of environmental/occupational/other exposure to one or more chemicals thatmay affect cognitive and/or motor function, including, but not limited to, heavymetals (arsenic [As], cadmium [Cd], lead [Pb], manganese [Mn], and mercury [Hg]),pesticides, solvents, or carbon monoxide.

• Clinical indications requiring >1 contrast enhanced magnetic resonance imaging (CE-MRI) every 6 months

• Pregnant or nursing (lactating) women

• Presence of any metal-containing joint implants/prostheses

In addition, for participants in either of the GBCA Arms only:

• Receipt of a GBCA or generic prior to study entry other than the specific GBCA to beadministered during the course of the study.

For participants in the Control Arm only:

• Participants with any previous exposure to a GBCA.

• Participants with any contraindication to UE-MRI examinations.