Background: Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA; gadoxetic acid disodium, Primovist, Bayer Healthcare, Berlin, Germany) is a gadolinium based contrast agent with hepatocyte specific properties. In patients scanned for hepatic metastasis using Gd-EOB-DTPA, it is important to differentiate hepatic metastasis with cysts and hemangiomas, which are the two most common benign lesions seen in the liver. Yet, in some cases it is difficult to differentiate these lesions. Purpose: The purpose of this study was to retrospectively investigate the usefulness of combining Fluid-attenuated inversion recovery (FLAIR) with Gd-EOB-DTPA enhanced MRI. Material and Methods: Gd-EOB-DTPA enhanced MRIs of 47 patients (19 male, 27 female) with a mean age of 68 years (range 32 - 85 years old) with a total of 121 lesions (68 cysts, 37 metastasis, 16 hemangiomas) were included in the study. T1WI, T2WI, heavy T2WI, dynamic contrast enhanced MRI, and FLAIR images of these lesions were evaluated. The patients were randomly divided into two groups (Groups A and B), and two independent radiologists were asked to give a diagnosis for each lesion. The radiologists were allowed to view FLAIR images for only Group B. Diagnostic performance regarding the differentiation of cysts, hemangiomas and metastases was assessed. MRI examinations were scanned using a 1.5 Tesla system (Echlon Vega, Hitachi,) with an 8 channel multiple array coil (RAPID body coil). Results: An statistically significant improvement (p < 0.05) of the specificity for cysts was seen from 71.9% (Group A) to 90.9% (Group B) for Reader 1, and 75.0% (Group A) to 93.3% (Group B) for Reader 2. No statistical differences were seen between the two groups for sensitivity and specificity of hemangiomas. Although no statistical difference was seen between the two groups, an improvement (77.8 in Group A to 97.2 in Group B for Reader 1, and 85.7 in Group A to 100 in Group B for Reader 2) was seen for the sensitivity of metastasis with the addition of FLAIR. Conclusion: An improvement of diagnostic accuracy, especially for cysts, was seen with the addition of FLAIR to Gd-EOB-DTPA enhanced MRI.
Hepatobiliary-specific contrast agents are a type of contrast agents used in magnetic resonance imaging (MRI). These agents are taken up by hepatocytes and excreted into the bile ducts. For these properties, a dynamic study as well as hepatobiliary phase images with good lesion to liver contrast can be obtained. There are two hepatobiliary specific contrast agents available; Gadolinium- ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA; Primovist, Bayer Healthcare) and gadobenate dimeglumine (Gd-BOPTA; MultiHance, Bracco). In Japan, only Gd-EOB-DTPA is available.
Gd-EOB-DTPA enhanced magnetic resonance imaging (MRI) has become an important tool for the imaging of the liver, and has been reported to have a good sensitivity and specificity for the diagnosis of hepatic lesions [
Fluid-attenuated inversion recovery (FLAIR) is an inversion recovery technique with a long inversion time (usually set to 2000 ms) which suppresses fluids. FLAIR has been used to suppress cerebrospinal fluid in brain MRI which facilitates lesion identification. Also, FLAIR can suppress the signal of cysts in liver MRI, and has been previously reported to be useful in differentiating cysts and hemangiomas in conventional MRI studies without contrast enhancement [
In this study, we retrospectively investigate the usefulness of FLAIR combined with Gd-EOB-DTPA enhanced MRI for the differentiation of metastasis, cysts and hemangiomas.
This retrospective study was approved by the ethics committee of our hospital. This study is in accordance with the principles of the Declaration of Helsinki.
We retrospectively reviewed records of 102 patients who were scanned for liver lesions by Gd-EOB-DTPA enhanced MRI between January and December 2010. Patients who received a dynamic contrast enhanced computed tomography (CT) study and/or abdominal ultrasound (US) within 1 month from the MRI who also underwent follow up MRI and/or CT and/or US 6 months after the initial MRI were included in the study. Patients who were diagnosed with metastasis, cysts, and hemangiomas were identified and included in the study.
Patients with no follow up studies after 6 months from the initial MRI study, and lesions that could not be proven by correlative studies were excluded (36 patients). Also, this study focused on the differentiation of metastases, cysts and hemangiomas, therefore patients with hepatocellular carcinoma (HCC) were excluded from the study (20 patients).
A total of 46 patients (19 male, 27 female) with a mean age of 68 years (range 32 - 85 years old) were included in the study.
The diagnostic criteria for the lesions were as follows:
For cysts 1) Imaging characteristics compatible with cysts (Echo-free lesion with distal enhancement) at US, and/or (Low attenuating area with no enhancement) at contrast-enhanced CT, and/or (High intensity area seen at T2WI and Heavy T2WI, and hypointensity or iso-intensity compared to the liver parenchyma on FLAIR with no enhancement in post-contrast images) at Gd-EOB- DTPA enhanced MRI (
For hemangiomas 1) Imaging characteristics compatible with hemangiomas (Well defined homogeneous hyperechoic appearance) at US, and/or (Low attenuating lesion with peripheral nodular enhancement at the early phase, persistent enhancement with subsequent fill in at delayed phase) at contrast enhanced CT, and/or (High intensity area at T2WI, Heavy T2WI, and FLAIR with peripheral nodular enhancement at the early phase, persistent enhancement with subsequent fill in at delayed phase) at Gd-EOB-DTPA enhanced MRI (
For metastasis 1) Imaging characteristics compatible with metastasis (Hypoechoic lesion) at US, and/or (Low attenuating mass with peripheral enhancement) at CT, and/or (High intensity on T2WI and FLAIR, Iso-intensity or high intensity compared to liver parenchyma on Heavy T2WI and peripheral enhancement on post-contrast images) at Gd-EOB-DTPA-enhanced MRI (
For patients with multiple lesions, five typical lesions were selected per patient for data analysis and electronic markers were placed on the lesions that were selected for evaluation. A total of 121 lesions (68 cysts, 37 metastases, 16 hemangiomas) were included in the study. For all of the lesions, the maximum diameter of the lesion measured on the hepatobiliary phase (
Group A | Group B | |
---|---|---|
Patient | 23 | 23 |
Age | 62 (45 - 80 y.o.) | 68 (32 - 85 y.o.) |
Cysts | 37 | 31 |
Metastasis | 14 | 23 |
Hemangiomas | 9 | 7 |
was 7 mm for cysts, 16 mm for metastasis, and 11 mm for hemangiomas (
Lesions were identified and selected by one radiologist with 9 years of experience in general radiology (M.H.).
MRI examinations were scanned using a 1.5 Tesla system (Echelon Vega, Hitachi, Tokyo, Japan) with a 8 channel multiple array coil (RAPID body coil).
All patients were scanned with the standard protocol for Gd-EOB-DTPA enhanced MRI at our institute. The sequences included in the protocol were as follows: Dual Echo T1WI, repetition time (TR)/echo time (TE), 2.3/4.6; flip angle, 80˚; field of view (FOV), 370 mm; matrix 224 × 208; 22 slices; slice thickness, 7 mm; gap, 0.7, Breath-hold fat saturated 3D T1-weighted gradient recall echo
Lesions | Number of lesions | Average size (mm) | Median size (mm) | Maximum Size (mm) | Minimum Size (mm) |
---|---|---|---|---|---|
Cysts | 68 | 7 | 6 | 24 | 3 |
Metastasis | 37 | 16 | 12 | 52 | 4 |
Hemangiomas | 16 | 11 | 8 | 39 | 4 |
(GRE), TR/TE, 4.3/1.8; flip angle, 12˚; FOV, 370 mm; matrix, 256,256; 64 slices; slice thickness, 6 mm; gap, −3 mm, respiratory-triggered T2-weighted fast spin echo (FSE), TR/TE, 3000/100; FOV, 370 mm; matrix 256 × 220; 22 slices; slice thickness, 7 mm; gap, 0.7 mm, breath-hold single shot-FSE, TR/TE, 13,000/100; FOV, 370 mm; matrix 224 × 200; 22 slices; slice thickness, 7 mm; gap, 0.7 mm; breath-hold FLAIR, TR/TE, 3000/100; inversion time (TI), 2200 ms, FOV, 370 mm; matrix 224 × 200; 22 slices; slice thickness, 7 mm; gap, 0.7 mm; scan time 20 sec. respiratory-triggered echo planner imaging-diffusion-weighted imaging, TR/TE, 3000/52; b = 500; FOV, 370 mm; matrix 128 × 96; 22slices; slice thickness, 7 mm; gap, 0.7 mm. The arterial phase, portal phase, late phase, and hepatobiliary phase was scanned 25 seconds, 60 seconds, 120 seconds and 15 minutes after injection of Gd-EOB-DTPA respectively with a fat saturated 3D-T1 weighted GRE sequence (
The intravenous bolus injection of Gd-EOB-DTPA administered was 0.025 mmol/kg (0.1 mL/kg bodyweight).
A commercially available picture archiving and reporting system (Rapideye Core, Toshiba, Tochigi, Japan) was used to evaluate the images.
One radiologist with 23 years of experience in abdominal radiology (T.G.), and one radiologist with 8 years of experience in general radiology (N.M.) evaluated the images and gave a diagnosis for each lesion that was marked for evaluation. The radiologists were informed that the study only included cysts, hemangiomas, and metastasis and were blinded of the clinical information as well as CT and ultrasound images.
To avoid recall bias, the patients were randomly divided into two groups Group A, and Group B. For Group A, the radiologists were allowed to evaluate the dynamic study combined with T2WI and heavy T2WI images, and for Group B, the dynamic study combined with T2WI, heavy T2WI and FLAIR images for the diagnosis for each lesion.
Statistical analysis was performed using a commercially available software package SPSS Statistics and EXCEL.
The difference in size of the types of lesions was compared using analysis of variance (ANOVA).
FOV [mm] | RFOV | matrix | Recon matrix | slices | [mm] | TE [ms] | TR [ms] | TI [ms] | FA | NSA | |||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
freq | phase | ||||||||||||
T2WI | Axial | 370 | 80 | 256 | 230 | 512 | 22 | 7 | 100 | 1650 | 90 | 2 | |
Heavy T2WI | Axial | 370 | 80 | 224 | 200 | 512 | 22 | 7 | 100 | 6506 | 90 | 1 | |
FLAIR | Axial | 370 | 80 | 224 | 200 | 512 | 22 | 7 | 100 | 9799 | 2200 | 90 | 1 |
THRIVE | Axial | 370 | 80 | 224 | 156 | 512 | 54 | 4 | 2.3 | 4.5 | 15 | 1 | |
THRIVE | Coronal | 380 | 80 | 208 | 145 | 512 | 54 | 4 | 2.3 | 4.5 | 15 | 1 | |
DWI | Axial | 370 | 80 | 128 | 90 | 256 | 22 | 7 | 56 | 2000 | 90 | 6 |
Sensitivity, specificity, positive predictive value, negative predictive values were calculated for cysts, metastasis, and hemagiomas for both Groups A and B. Mantel Haenszel procedure was used to evaluate the effect of FLAIR for the diagnosis of the lesion between Group A and B.
For each test a two-tailed P value of 0.05 was considered to indicate a statistically significant difference.
Diagnosis (
Reader 1 correctly diagnosed 28/37 cysts in Group A, compared to 28/31 in Group B. 8 cysts were diagnosed as hemangiomas, and 1 cyst was diagnosed as a metastasis in Group A. 3 cysts were diagnosed as hemangiomas in Group B. Reader 2 correctly diagnosed 30/37 cysts in Group A, compared to 29/31 in Group B.6 cysts were diagnosed as hemangiomas and 1 cyst was diagnosed as a metastasis in Group A. 2 cysts were diagnosed as hemangiomas in Group B.
Reader 1 correctly diagnosed 6/9 hemangiomas in Group A, compared to 4/7 in Group B. 3 hemangiomas were diagnosed as metastasis in Group A, and 3 hemangiomas were diagnosed as metastases in Group B. Reader 2 correctly diagnosed 7/9 hemangiomas in Group A, compared to 5/7 in Group B. 1 hemangiomas were diagnosed as cyst and 1 as a metastasis in Group A. 2 hemangiomas were diagnosed as cysts in Group B.
Reader 1 correctly diagnosed 14/14 metastases in Group A, compared to 22/23 in Group B. 1 metastasis was diagnosed as hemangioma in Group B. Reader 2 correctly diagnosed 12/14 metastasis in Group A, compared to 22/23 in Group B. 1 metastasis was diagnosed as cyst and 1 metastasis was diagnosed as a hemangioma in Group A. 1 metastasis was diagnosed as hemangioma in Group B.
Reader 1 | |||||||
---|---|---|---|---|---|---|---|
Lesion | |||||||
Cyst | Hemangioma | Metastasis | |||||
Group A | Group B | Group A | Group B | Group A | Group B | ||
Diagnosis | Cyst | 28 | 28 | 0 | 0 | 0 | 0 |
Hemangioma | 8 | 3 | 6 | 4 | 0 | 1 | |
Metastasis | 1 | 0 | 3 | 3 | 14 | 22 |
Reader 2 | |||||||
---|---|---|---|---|---|---|---|
Lesion | |||||||
Cyst | Hemangioma | Metastasis | |||||
Group A | Group B | Group A | Group B | Group A | Group B | ||
Diagnosis | Cyst | 30 | 29 | 1 | 2 | 1 | 0 |
Hemangioma | 6 | 2 | 7 | 5 | 1 | 1 | |
Metastasis | 1 | 0 | 1 | 0 | 12 | 22 |
The sensitivity for cysts was 100% for both Group A and Group B for Reader 1 and 93.8% for Group A and 93.5% for Group B for Reader 2. The specificity for cysts increased from 71.9% (Group A) to 90.9% (Group B) for Reader 1, and 75.0% (Group A) to 93.3% (Group B) for Reader 2. A statistical difference was seen in the diagnosis of cysts between Group A and Group B.
The sensitivity and specificity for hemangiomas were 42.9 and 93.5 for Group A, 50 and 94.3 for Group B respectively for Reader 1. For Reader 2, the sensitivity and specificity were 50.0 and 95.7 for Group A, 62.5 and 96.2 for Group B respectively. No statistical difference was seen.
The sensitivity and specificity for metastasis were 77.8 and 100 for Group A, 88 and 97.2 for Group B respectively for Reader 1. For Reader 2, the sensitivity and specificity were 85.7 and 95.7 for Group A, 100 and 97.4 for Group B respectively. Although no statistical difference was seen between the two groups, an improvement was seen for the sensitivity of metastasis with the addition of FLAIR.
The liver is the second most common site of metastasis after regional lymph nodes, making it the most common malignancy found in the liver. Therefore, it is important to differentiate cysts and cavernous hemangiomas, the two most common benign lesions found in the liver, with metastases. CT, US, and MRI has been mainly used to detect and differentiate these lesions.
CT is a widely available method with the ability to scan wide areas of the body in short scan times. Therefore, it is possible to evaluate the liver as well as other
Reader 1 | Cyst | Hemangioma | Metastasis | |||
---|---|---|---|---|---|---|
Group A | Group B | Group A | Group B | Group A | Group B | |
Sensitivity | 100 | 100 | 42.9 | 50.0 | 77.8 | 88.0 |
Specificity | 71.9 | 90.9 | 93.5 | 94.3 | 100 | 97.2 |
PPV | 75.7 | 90.3 | 66.7 | 57.1 | 100 | 95.7 |
NPV | 100 | 100 | 84.3 | 92.6 | 91.3 | 92.1 |
Reader 2 | Cyst | Hemangioma | Metastasis | |||
---|---|---|---|---|---|---|
Group A | Group B | Group A | Group B | Group A | Group B | |
Sensitivity | 93.8 | 93.5 | 50.0 | 62.5 | 85.7 | 100 |
Specificity | 75.0 | 93.3 | 95.7 | 96.2 | 95.7 | 97.4 |
PPV | 81.1 | 93.5 | 77.8 | 71.4 | 85.7 | 95.7 |
NPV | 91.3 | 93.3 | 86.3 | 94.4 | 95.7 | 100 |
Statistical difference between Group A and Group B (p < 0.05) | |
---|---|
Cyst | 0.0290 |
Hemangioma | 0.3892 |
Metastasis | 0.6035 |
Overall | 0.0569 |
metastasis and primary site of the malignancy. By adding dynamic contrast enhancement, the vascularity of the tumor can be depicted, and is useful for the differentiation of liver lesions. Yet, CT scans involve radiation exposure, and has been reported to have a lower sensitivity and specificity compared to MRI [
Conventional B-mode abdominal ultrasound is a widely available method with no exposure to radiation, and is considered one of the first choice techniques for liver imaging. Also, with the introduction of microbubble enhanced ultrasound, overall diagnostic accuracy has increased [
Conventional MRI using T2WI and Heavy T2WI has been described in previous reports for the differentiation of hepatic lesions with a sensitivity and specificity of for hemangiomas and cysts [
Gd-EOB-DTPA is a liver specific contrast agent. Uptake of the contrast media into heptatocytes enhances the liver parenchyma, and lesions without hepatocytes remain unenhanced in the hepatobilliary phase. Therefore, an excellent lesion to liver contrast is obtained. With the introduction of Gd-EOB-DTPA, sensitivity and specificity of liver lesions has increase compared to conventional MRI [
The use of FLAIR has previously been reported to be useful for the differentiation between cysts and hemangiomas in unenhanced MRI [
In this study, although the size of cysts were statistically smaller than metastases and hemangiomas, the diagnostic performance that was obtained was sensitivity 100%, specificity 97%, which was comparable to or slightly better than the results of the previous study by Sasaki et al. which was conducted with MRI without contrast enhancement (sensitivity 89.5%, specificity 97.5) [
The differentiation of hemangiomas and metastasis is sometimes difficult [
Three cysts were interpreted as hemangiomas for Reader 1 and two cysts were interpreted as hemangiomas for Reader 2. The signal of these cysts was not suppressed on FLAIR images. These cysts could have been filled with protein rich such as ciliated foregut cysts, or could have contained hemorrhagic content [
There are several limitations to this study. The number of lesions that were included in the study was relatively small (n = 121), and the number of hemangiomas were small (n = 16) compared to the other lesions. A larger number of lesions could have shown statistical differences for sensitivity and specificity of hemangiomas and metastases between the two groups. Hepatic lesions with lower incidences compared to cysts, hemangiomas, and metastasis such as focal nodular hyperplasia, hepatobiliary carcinoma, cholangiocarcinomas were not included in this study. However, our study focused on the differentiation of metastasis from benign lesions with high incidences, which are seen in daily practice. Pathological proof for the lesions could not be obtained for most of the lesions, because most of the lesions included in our studies were benign. Yet, we believe adequate correlative studies and follow up was obtained for the lesions included in the study.
In conclusion, an improvement of diagnostic accuracy for cysts was seen with the addition of FLAIR to Gd-EOB-DTPA enhanced MRI. This improvement decreased the cases of small metastasis diagnosed as cysts. However, a minimal improvement was seen for the differentiation between small hemangiomas and metastases.
Hasegawa, M., Sugiyama, M., Murata, N., Nagamoto, M. and Gomi, T. (2017) FLAIR in Gd-EOB- DTPA Enhanced MRI: Does It Make a Difference? Open Journal of Radiology, 7, 130-142. https://doi.org/10.4236/ojrad.2017.72015