Hepatocellular Carcinoma
Conditions
Keywords
Hepatocellular Carcinoma, Hepatoma, Liver Cancer, Adult, Liver Cell Carcinoma, Liver Cell Carcinoma, Adult, HCC
Brief summary
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.
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.
Interventions
PROCEDUREliver 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
DEVICEfree-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
Sponsors
Case Comprehensive Cancer Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Arterial Fraction | 1 day, At time of Research MRI | 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. |
| Distribution Volume (DV) | 1 day, At time of Research MRI | 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 |
| Mean Transit Time (MTT) | 1 day, At time of Research MRI | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Free Breathing Quantification of Relaxation Parameters | Up to 1 year | Quantified and validated relaxation parameters when creating T1 (spin-lattice) and T2 (spin-spin) weighted images |
| Minimal Breathhold Time | 1 year | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dynamic Contrast Enhanced MRI 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.
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
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 | 34 |
| Free-Breathing Quantification of Relaxation Parameters 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
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 | 18 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | lesion impacted by previous treatment | 1 | 1 |
| Overall Study | Malignant lesions not HCC nor Metastatic | 1 | 1 |
| Overall Study | No Confirmed Diagnosis | 0 | 3 |
| Overall Study | No Visible Lesion or Pathological Finding | 4 | 0 |
| Overall Study | Omitted for Severe Image Artifacts or Patient Non-compliance | 11 | 12 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Dynamic Contrast Enhanced MRI | Free-Breathing Quantification of Relaxation Parameters | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 16 Participants | 5 Participants | 21 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants | 13 Participants | 31 Participants |
| Lesion type Benign | 3 Participants | 2 Participants | 5 Participants |
| Lesion type HCC | 10 Participants | 9 Participants | 19 Participants |
| Lesion type Metastatic Cancer | 16 Participants | 3 Participants | 19 Participants |
| Lesion type No confirmed diagnosis, other malignant, or no visible lesion/path | 5 Participants | 4 Participants | 9 Participants |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment United States | 34 participants | 18 participants | 52 participants |
| Sex: Female, Male Female | 12 Participants | 5 Participants | 17 Participants |
| Sex: Female, Male Male | 22 Participants | 13 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 34 | 0 / 18 |
| other Total, other adverse events | 0 / 34 | 0 / 18 |
| serious Total, serious adverse events | 1 / 34 | 0 / 18 |
Outcome results
Primary
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.
Time frame: 1 day, At time of Research MRI
Population: Evaluable participants (those who completed study with applicable lesions). Note - There were only sufficient number of participants to statistically compare HCC and Metastatic lesion groups due to the low number of benign lesions. No data are available for the Free-breathing Quantification of Relaxation Parameters for reasons listed in participant flow section - primarily relating to image blurring and artifacts.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dynamic Contrast Enhanced MRI - HCC Lesions | Arterial Fraction | 79.8 percentage of arterial fraction | Standard Deviation 12.9 |
| Dynamic Contrast Enhanced MRI - Metastatic Lesions | Arterial Fraction | 72.2 percentage of arterial fraction | Standard Deviation 20.4 |
| Dynamic Contrast Enhanced MRI - Benign Lesions | Arterial Fraction | 73.6 percentage of arterial fraction | Standard Deviation 15.9 |
p-value: 0.211t-test, 2 sided
Primary
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
Time frame: 1 day, At time of Research MRI
Population: Evaluable participants (those who completed study with applicable lesions). Note - There were only sufficient number of participants to statistically compare HCC and Metastatic lesion groups due to the low number of benign lesions. No data are available for the Free-breathing Quantification of Relaxation Parameters for reasons listed in participant flow section - primarily relating to image blurring and artifacts.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dynamic Contrast Enhanced MRI - HCC Lesions | Distribution Volume (DV) | 29.9 percentage of DV | Standard Deviation 13 |
| Dynamic Contrast Enhanced MRI - Metastatic Lesions | Distribution Volume (DV) | 53.8 percentage of DV | Standard Deviation 19.3 |
| Dynamic Contrast Enhanced MRI - Benign Lesions | Distribution Volume (DV) | 61.8 percentage of DV | Standard Deviation 20.9 |
p-value: <0.01t-test, 2 sided
Primary
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
Time frame: 1 day, At time of Research MRI
Population: Evaluable participants (those who completed study with applicable lesions). Note - There were only sufficient number of participants to statistically compare HCC and Metastatic lesion groups due to the low number of benign lesions. No data are available for the Free-breathing Quantification of Relaxation Parameters for reasons listed in participant flow section - primarily relating to image blurring and artifacts.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dynamic Contrast Enhanced MRI - HCC Lesions | Mean Transit Time (MTT) | 12.0 seconds | Standard Deviation 3.1 |
| Dynamic Contrast Enhanced MRI - Metastatic Lesions | Mean Transit Time (MTT) | 44.6 seconds | Standard Deviation 25.7 |
| Dynamic Contrast Enhanced MRI - Benign Lesions | Mean Transit Time (MTT) | 5.8 seconds | Standard Deviation 2 |
p-value: <0.01t-test, 2 sided
Secondary
Free Breathing Quantification of Relaxation Parameters
Quantified and validated relaxation parameters when creating T1 (spin-lattice) and T2 (spin-spin) weighted images
Time frame: Up to 1 year
Population: Quality of images were poor and could not be used for analysis
Secondary
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.
Time frame: 1 year
Population: Although the study team worked on the development of this technology as part of an NIH grant, this technology was not utilized as a part of this study so no data were collected.