Assessment of Novel MRI Quantification Free Breathing Technique in Evaluation of Liver Lesions

The primary objective of this study is to develop and validate simultaneous free-breathing 4D fat and water quantification and quantitative dynamic contrast enhanced perfusion in the liver. Secondary aims include developing and validating free breathing quantification of relaxation parameters T1 and T2, and developing and validating a minimal breath-hold (< 8 s) high quality diffusion exam using highly accelerated steady state diffusion imaging sequences. Investigators aim to scan 100 subjects receiving liver biopsies as a part of their standard care and another 70 subjects with known benign lesions. The study is greater than minimal risk.

Study Overview

• Status: Completed
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Procedure: liver biopsy; Device: free-breathing MRI

Detailed Description

The investigators hypothesize that a quantitative and near free-breathing MRI approach with Hepatocellular carcinoma (HCC) patients will lead to improved tissue characterization, resulting in fewer ambiguous readings and thus fewer biopsies. As each component of the proposed methodology has been experimentally validated in the investigators preliminary work, the next appropriate step would be to evaluate the clinical feasibility of the exam. The investigators goal is to test the ability of quantitative MRI techniques to provide high quality images of the liver and to differentiate liver lesions from one another in a time frame shorter than a current clinical exam.

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• No contraindications to getting contrast enhanced MRI examinations.
• GFR ≥ 40.

Exclusion Criteria:

• Patients with ferromagnetic or otherwise non-MRI compatible aneurysm clips.
• The presence of an implanted pacemaker or implanted defibrillator device
• Patients with contraindications for MRI due to embedded foreign metallic objects. Bullets, shrapnel, metalwork fragments, or other metallic material adds unnecessary risk to the patient.
• Pregnancy. Regular clinical practice already excludes pregnant patients from gadolinium contrast due to unknown effects on the fetus. The current clinical practice will be applied - patients will be verbally screened and asked if they think they could be pregnant. If the answer is yes, then the patient will be excluded from the study. If the patient is uncertain about the pregnancy status, she will be given an option to undergo a pregnancy test or not participate in the study altogether. Patients who self report that they are not pregnant will be allowed to participate in the study. This procedure is based on current department policy guidelines.
• Implanted medical device not described above that is not MRI-compatible;
• Known history of claustrophobia;
• Known history of allergic reaction to Magnetic Resonance contrast material;
• Late stage renal failure with estimated glomerular filtration rate (eGFR) of less than 30 mL/min/1.73 m2 based on patient's serum creatinine due to the significantly increased risk of nephrogenic systemic fibrosis (NSF). ('Past' 3 months timeframe will be used to calculate the eGRF).
• Minors will be excluded.
• Prisoners and members of other vulnerable populations will be excluded from this study. The subject selection population will not regularly include prisoners and other vulnerable population members as these populations will not provide any additional unique information to or uniquely benefit from the study. Non-english speaking population will be excluded from the study due to lack of sufficient resources to pay for translator and interpreter services.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HCC or metastatic Liver Lesions; Patients with HCC or metastatic liver lesions who are refered to the abdominal imaging and biopsy clinic will have a liver biopsy performed. 3-5 days after a clinical MRI indicating a cancerous lesion, patients will return for the free-breathing MRI and a liver biopsy. These images will be compared to the clinical MRI and to images of the benign lesions.	Procedure: liver biopsy; patients with HCC or metastatic lesions will have a liver biopsy performed after the experimental MRI. This biopsy will be examined to confirm the imaging results; Device: free-breathing MRI; All patients will be asked to come in for an MRI scan using techniques developed which minimize the time a patient has to hold their breath to image the liver to <8 seconds and validate quantifiable techniques which improve liver image quality; Other Names: experimental MRI
Active Comparator: Benign Liver Lesion; Patients with benign liver lesions will be referred to the study team. 3-5 days after a clinical MRI an experimental, free-breathing MRI will be performed on these patients. The results will be compared to their clinical MRI images and to images of HCC or metastatic lesions	Device: free-breathing MRI; All patients will be asked to come in for an MRI scan using techniques developed which minimize the time a patient has to hold their breath to image the liver to <8 seconds and validate quantifiable techniques which improve liver image quality; Other Names: experimental MRI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Arterial Fraction	Dynamic Contrast Enhanced MRI data were used to calculate three quantitative perfusion properties using a dual input, single tissue compartment model of gadolinium based contrast agents in the liver in HCC, metastatic, and benign lesions. One of these quantitative perfusion properties is Mean Arterial fraction, which is the proportion of blood flow derived from hepatic artery.	1 day, At time of Research MRI
Distribution Volume (DV)	Dynamic Contrast Enhanced MRI data were used to calculate three quantitative perfusion properties using a dual input, single tissue compartment model of gadolinium based contrast agents in the liver in HCC, metastatic, and benign lesions. One of these quantitative perfusion properties is DV. DV corresponds to the volume of extracellular, extravascular space in a tissue which is a measure of the tissue cellularity	1 day, At time of Research MRI
Mean Transit Time (MTT)	Dynamic Contrast Enhanced MRI data were used to calculate three quantitative perfusion properties using a dual input, single tissue compartment model of gadolinium based contrast agents in the liver in HCC, metastatic, and benign lesions. One of these quantitative perfusion properties is MTT. MTT corresponds to the average time, in seconds, that red blood cells spend within a determinate volume of capillary circulation	1 day, At time of Research MRI

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Free Breathing Quantification of Relaxation Parameters	Quantified and validated relaxation parameters when creating T1 (spin-lattice) and T2 (spin-spin) weighted images	Up to 1 year
Minimal Breathhold Time	The minimum time (in seconds) a patient must hold their breath to produce quality liver images during an MRI. Developing and validating a minimal breath-hold (< 8 s) high quality diffusion exam using highly accelerated steady state diffusion imaging sequences.	1 year

Collaborators and Investigators

• Sponsor: Case Comprehensive Cancer Center
• Investigators: Principal Investigator: Vikas Gulani, MD, Case Comprehensive Cancer Center

Publications and helpful links

General Publications

• Pahwa S, Liu H, Chen Y, Dastmalchian S, O'Connor G, Lu Z, Badve C, Yu A, Wright K, Chalian H, Rao S, Fu C, Vallines I, Griswold M, Seiberlich N, Zeng M, Gulani V. Quantitative perfusion imaging of neoplastic liver lesions: A multi-institution study. Sci Rep. 2018 Mar 21;8(1):4990. doi: 10.1038/s41598-018-20726-1.

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Actual): December 3, 2019
• Study Completion (Actual): December 3, 2019

Study Registration Dates

• First Submitted: March 20, 2014
• First Submitted That Met QC Criteria: March 24, 2014
• First Posted (Estimate): March 26, 2014

Study Record Updates

• Last Update Posted (Actual): June 30, 2022
• Last Update Submitted That Met QC Criteria: June 29, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Hepatocellular Carcinoma; HCC; Hepatoma; Liver Cancer, Adult; Liver Cell Carcinoma; Liver Cell Carcinoma, Adult
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: CASE3213

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No