A total of fifty-five (55) patients with liver cirrhosis will be enrolled in this study to produce and validate dedicated Ga-PSMA-PET/MRI acquisition protocols.

The specific hypotheses include:

• Ga-PSMA PET/MRI may allow robust and reproducible noninvasive in vivo quantitation of hepatic macro and microhemodynamics in cirrhotic patients
• Dedicated simultaneously acquired DWI sequences might quantitate liver fibrosis and improve hemodynamic quantitation.
• Ga-PSMA PET/MRI may allow noninvasive and reproducible quantitation of portal venous hypertension and predict its evolution, as well as response to treatments
• Ga-PSMA PET/MRI may improve noninvasive and reproducible qualitative and quantitative assessment of liver function, structure, nodules and predict evolution of cirrhosis

[68Ga]Ga-PSMA-11(Ga-PSMA) is a novel radiotracer approved by the FDA in late 2020 to investigate prostate cancer in men. This compound targets the prostate-specific membrane antigen, which unlike the name suggests, has been detected in other anatomical regions, mainly associated with neoangiogenesis. The high affinity of PSMA toward neoangiogenesis can play several roles in imaging liver cirrhosis. In particular, it may highlight neovasculature and help distinguish microhemodynamic changes caused by shunting from those caused by increased vascular permeability associated to neoangiogenesis. Thus, Ga-PSMA may improve the interpretation of MRp maps, of DWI data (which is also influenced by microperfusion) and might add more confidence on Li-Rad classifications.

For each candidate patient subject, the study staff will first contact the treating clinician to inquire as to their willingness to allow investigators to approach the subject to participate in this study. The clinician will initially introduce the study to the patient and will obtain the patient's permission to be contacted by the study staff. One of the investigators or other study staff will then approach the subjects in accordance with PHRC policy. At the time of initial discussions about potentially participating in this study, the investigators will make it clear to potential subjects that the study scan is performed at the Charlestown Navy Yard to allow them to decide if travel associated with participation is too inconvenient. Subjects will be informed that a decision to participate or not in the PET/MRI protocol will not affect their care within MGH or any other Mass General Brigham facility. Informed consent will be obtained from the subjects by licensed physician principal investigator, licensed physician co-investigator, or licensed nurse practitioners listed as co-investigators with backup from a licensed physician investigator listed on study staff.

PET/MRI images will be acquired using the Biograph mMR combined 3 Tesla PET/MRI scanner. The image quality on these 3 Tesla devices will be very high, typical, or better than any other standard clinical MRI system. Subjects will be asked to lie still for the duration of the study. The investigators expect the entire imaging session to last about 80 minutes and not to exceed 120 minutes.

The investigators will be comparing:

1. Different sequences, acquisition protocols and reconstruction modeling in term of image quality, reduction of artifacts, improved signal and contrast to noise ratios, reproducibility of the quantitative features.
2. PSMA-PET/MRI quantitative and qualitative features, including hybrid biomarkers obtained incorporating PSMA uptake with MRp and/or 4D-MRI and/or DWI extracted parameters, with clinical data that provide insights into liver function and liver hemodynamics
3. PSMA-PET/MRI qualitative and quantitative features (for example vascular permeability or median velocity), including hybrid biomarkers, with clinical data to explore possibility of assessing liver function, quantify fibrosis, facilitate Li-Rad classification, measure hemodynamics in cirrhotic patients including those treated/ to be treated for portal hypertension.
4. Comparison of fused Ga-PSMA PET/MRI images with stand-alone MRI images and stand-alone PET images obtained in the same scan in terms of qualitative and quantitative imaging features, for example confidence in characterization of band-like fibrosis or differentiation of mild from moderate degree of fibrosis.
5. The investigators will also follow up patients to ascertain if Ga-PSMA PET/MRI result might have impacted on clinical management.

Descriptive statistics will be used to compare the performance (detection rates, sensitivity, and specificity) of PET/MRI and MRI alone. When calculating sensitivity and specificity for each imaging modality, the gold standard will be considered whole-liver pathology for patients who undergo liver transplant; or biopsy/surgical pathology results in patients that do not undergo liver transplantation but are directed to biopsy; or finally imaging follow-up in patients who undergo follow-up only. No biopsy or image follow-up will be ever ordered for the sake of this study. They will be ordered only for standard clinical care. Means and standard deviations or median and (IQR) will be reported for continuous variables according to the variable distributions. Categorical variables will be reported as counts and proportions, and 95% Confidence Intervals will be included when applicable. A p-value <0.05 will be considered statistically significant. For the primary endpoint analysis, confusion matrices will be constructed comparing PET/MRI to PET alone ant to MRI alone. Each lesion described by the readers of the imaging modalities will then be classified accordingly into true positive, false positive, true negative or false negative. Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value will then be computed using the adequate proportions as estimates. Additional parameters that will be evaluated include region of interest location, size, apparent diffusion coefficient value, and standardized uptake value, and quantitative MRp metrics.

Inclusion Criteria:

• Liver cirrhosis as diagnosed by imaging and/or clinical data, including pathology

Exclusion Criteria:

• Any contraindication to PET, as in attached screening form
• Any contraindication to MRI, as in attached screening form
• Any contraindication to gadolinium-based contrast agent, including allergy to gadolinium, as in attached screening forms.
• Pregnancy
• Breast feeding.
• Cumulative radiation exposure for research studies during the prior 12 months, combined with the exposure from this study, > 50 mSv
• Inability to fit in the scanner: weight > 300 lbs or BMI > 33

Fifty-five subjects will be recruited. All subjects recruited for the study will be able to withdraw from the study at any time.

Healthy Volunteers: The investigators will not be recruiting or enrolling healthy volunteers in this study. Patients with liver cirrhosis: Fifty-five (55)