This study is being done to help doctors improve how they treat liver tumors that cannot be removed by surgery or treated with standard ablation techniques. The researchers want to find out the best amount of radiation that needs to be delivered to completely destroy (or ablate) parts of the liver that have cancer.

Currently, doctors use Yttrium-90 (Y90) radiation segmentectomy, a treatment that delivers tiny radioactive beads into the blood vessels feeding the liver tumor. These beads give off radiation that helps kill the cancer cells from the inside, right where the tumor is located. This approach allows doctors to target the tumor very precisely, while keeping the rest of the liver as healthy as possible. However, the exact dose needed to fully ablate a tumor without damaging healthy liver tissue is not well established.

To answer this, the study team will use specialized imaging before and after treatment to evaluate how the radiation is distributed in the liver and how the liver responds over time. These include PET/CT or PET/MRI scans, which are standard medical imaging tests that are not considered experimental. During these scans, a small amount of a safe radioactive substance is injected into their vein. This helps show where the Y90 beads are in their liver.

In a PET/CT scan, two types of imaging are performed during the same session. The PET scan detects signals from the radioactive substance and shows how your liver is functioning at a molecular level. The CT scan, which uses x-rays to create detailed cross-sectional images of the body, provides a precise anatomical map that helps localize these functional signals. Together, they give a clear picture of both the structure and activity within the liver.

PET/MRI works similarly but uses magnetic fields and radio waves instead of x-rays. It combines the functional information from the PET scan with the highly detailed soft-tissue images from MRI, which can be especially useful in evaluating the liver. Both imaging techniques are done during a single visit, with the PET component typically performed at the same time as the CT or MRI, depending on which machine is used. They will also have a liver MRI with dual contrast (Eovist and extracellular gadolinium), another standard imaging procedure. MRI uses magnets and radio waves to take detailed pictures of your liver. Eovist is a special dye injected into their vein during the scan that helps highlight liver tissue and shows how well different parts of their liver are functioning. Extracellular gadolinium is a more general contrast agent that enhances blood vessels and tissues, providing complementary information. This helps the doctors confirm whether the tumor area was completely treated.

The goal is to determine the safest and most effective dose of radiation to fully treat cancer while preserving healthy liver tissue. This information may help doctors treat future patients more precisely and safely.

Yttrium-90 and the imaging methods used in this study, including PET/CT, PET/MRI, and dual contrast MRI, are FDA-approved.

Inclusion Criteria:

• Diagnosis of hepatocellular carcinoma (HCC), cholangiocarcinoma, or liver-dominant metastatic disease not amenable to surgical resection or ablation.
• Age ≥18 years.
• Tumor size ≤5 cm requiring treatment of ≤2 Couinaud segments.
• Child-Pugh class A or B liver function
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Adequate organ and bone marrow function as defined below:
• Leukocytes (WBC) ≥ 3,000/mcL
• Absolute neutrophil count (ANC) ≥ 1,500/mcL
• Hemoglobin ≥ 9 g/dL
• Platelets ≥ 50,000/mcL
• Total bilirubin ≤ 3.0 mg/dL
• AST ≤ 100 U/L, ALT ≤ 120 U/L
• Creatinine ≤ 2.0 mg/dL or estimated GFR ≥ 40 mL/min/1.73 m²
• Ability to undergo imaging and laboratory evaluations required by the study.
• Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

• Extrahepatic metastases.
• Pregnant or breastfeeding individuals.
• Tumors requiring treatment of more than two Couinaud segments.
• Known hypersensitivity to gadolinium-based contrast agents.
• Contraindications to MRI (e.g., incompatible pacemakers, claustrophobia unresponsive to sedation).
• Coagulopathy or clinical instability precluding angiographic intervention.
• Prisoners or individuals under legal custody.
• Adults unable to consent.
• Individuals under 18 years of age.