Color Doppler Flow Imaging of Hepatic Focal Nodular Hyperplasia Masatoshi Kudo, MD, Shusuke Tomita, MD, Kazushi Minowa, RT, Hitoshi Tochio, RT, Keiko Shimada, RT, Jun Mimura, MD, Yoshihiro Okabe, MD, Hiroshi Kashida, MD, Masahiro Hirasa, MD, Akio Todo, MD
Focal nodular hyperplasia (FNH) is a rare benign hy~ pervascular lesion 1 that is a tumor-like condition but is not a true neoplasm, It is sometimes found incidentally, but occasionally symptoms are noted when it is large in size. Although its vascular architecture is character~ istic,u FNH is difficult to demonstrate by noninvasive modalities, such as computed tomography (CT), magnetic resonance (MR) imaging, and abdominal sonography, and sometimes even by angiography." 4 Recently, Doppler sonography,u especially color Doppler imaging, was introduced as a new diagnostic technique capable of characterizing hepatic tumors noninvasively.7-10 However, to our knowledge the appearance of FNH on color Doppler imaging has not been reported previously. We report the findings in one such patient.
CASE REPORT This 50 year old man was referred to our hospital for further evaluation of a hepatic nodule that was detected incidentally during abdominal sonography. The results of blood tests showed normal liver function, and the physical examination findings were normal. A plain sonogram (Fig. lA) revealed a single homogeneous hypoechoic nodule 3.0 em in diameter Received January 13, 1992, from the Division of Gastroenterology, Department of Medidne (M. K ~ S.T., J.M., Y.O .• H.K.. M.H., A.T. ), and Section of Abdominal Ultrasound (K.M., H.T., K.S.), Kobe City General Hospital, Kobe, japan. Reviied manuscript accepted for publication April29, 1992. Address correspondence and reprint requests to M. Kudo,. MD, Division of Gastroenterology, Department of Medidne, Kobe City General Hospital, 4-6, Minatojima-Nakamachi, Chuo-ku, Kobe 650, Japan.
with a clear margin at the subcapsular region in the anteroin~ ferior area of the right lobe of the liver. CT showed a hypodense mass. A CT scan obtained with contrast enhance· ment demonstrated it to be a high-attenuation mass. The focal defect was demonstrated on radiocolloid liver scan. On MR imaging, the lesion was found to be homogeneously hypointense, with an irregular margin on Tl -weighted sequences (spin-echo, 600/15 TR/TE) and inhomogeneously hyperintense on T2-weighted sequences (spin-echo, 2000/ 70) obtained with a superconducting imager operated at 1.5 T (Magnetom, Siemens, Erlangen, Germany). The early ar· terial phase of hepatic angiography revealed a tortuous dilated artery entering the central part of the lesion, but a spokewheel appearance was not present. The capillary phase of angiography revealed the nodule to be hypervascular, with a faint stain. Sonographic angiography4 showed that the arterial supply arose from the center of the nodule 1 to 2 seconds after the infusion of C02 microbubbles (early arterial phase) (Fig. lB, C). The dilated artery observed at the center of the nodule branched toward the periphery, mainly in two directions; toward the transducer and away from it (Fig. 1B, C). The arterial supply gradually radiated to the periphery during the next few seconds. A hypervascular stain was observed 10 seconds after the infusion of col microbubbles (capillary phase) (Fig. 1D), which is diagnostic of FNH. 4 Color Doppler imaging with a Toshiba SSA 270A (Toshiba, Tokyo, Japan) using a 3.75 MHz transducer dearly demonstrated a dilated color flow signal at the center of the nodule together with two branches: one signal approached the transducer while the other signal went in the opposite direction within the lesion (Fig. 2). corresponding exactly to the findings of sonographic angiography. Both signals showed pulsatile ar· terial waveforms on a pulsed Doppler spectral analysis (Figs. 3, 4). Percutaneous liver biopsy under sonographic guidance confirmed the diagnosis of FNH. The hepatocytes were normal, and the bile duct proliferation and connective tissue, which is considered to be fibrous septa radiating to the
© 1992 by the American Institute of Ultrasound in Medicine • J Ultrasound Med 11:553-557, 1992 • 0278-4297/92/$3.50
554
J Ultrasound Med 11:553- 557, 1992
COLOR DOPPLER IMAGING OF FNH
A
B
c
D
Figure 1 A, An intercostal scan of a plain sonogram shows a 3.0 em hypoechoic nodule in the subcapsular region of the right lobe of the liver (arrows). A hyperechoic spot is barely seen at the center of the lesion (a"ow). B, Sonographic angiography shows the dilated artery in the central zone with two branches (arrows) 1 s after the intra-arterial infusion of C02 microbubbles. C, Sonographic angiography 2 s after the infusion shows a gradual centrifugal filling originating in the central zone. D, Sonographic angiography 10 s after the inlu§ion shows hypervascular staining.
Figure 2 A dilated flow signal that enters the central zone of the nodule (a"owheads) and that branches into two blood flow signals (a"ows) is demonstrated on color Doppler flow imaging.
J Ultrasound Med 11:553- 557, 1992
KUDO ET AL 555
Figure 3 The blood flow signal of the branch that approaches the transducer appears as a pulsatile wave form on the pulsed Doppler spectral analysis, suggesting it is an artery.
periphery from the central scar, were observed. During a 2 year follow-up, the nodule remained stable and has not enlarged.
DISCUSSION The peculiar arterial vasculature of FNH demonstrates a feeding artery that enters the central zone, branches peripherally, and supplies the lesion centrifugallyP The study revealed that the branches originate from the central fibrous zone. 2 Although sonography, CT, and MR imaging provide no findings specific to the diagnosis of FNH, FNH can be confirmed angiographically if the distinctive arteriographic centrifugal filling pattern, the so-called spokewheel sign, can be demonstrated.1 •4 However, although this finding is detected angiographically in 57 to 90% of the cases with extensive FNH, 1·4 it becomes more difficult to detect this pattern angiographically in small areas of FNH, espe24 cially when the diameter is less than 3 cm. 1• • Sonographic angiography with the intra-arterial infusion of C02 microbubbles is an imaging technique 4 that combines sonography and angiography. This new
technique permits the accurate evaluation of tumor hemodynamics. Sonographic angiography demonstrates the arterial vascular pattern of FNH as an early central hypervascular supply with centrifugal filling to the periphery and uniform staining at the capillary phase. This finding is highly specific for FNH (sensitivity, 100%; specificity, 100%) and has not been observed in any other benign or malignant tumor. 4 ·u Because the images that are obtained with sonographic angiog· raphy are tomographic images, exactly the same as color Doppler imaging, sonographic angiography can be assumed to be a gold standard in analyzing the origin of the color flow signals. Color Doppler flow imaging, which was originally developed for viewing the heart and large blood ves· sels, provides information on blood flow, including a pulsed Doppler spectral analysis, and provides an image of the tumor on a single sonogram. Thus, it is possible to obtain simultaneously information previously available only with two separate examinations, sonography and angiography. Taylor and colleaguess suggested that Doppler sonography is a useful clinical method for the noninvasive tissue characterization of hepatic tumors, and they predicted that the application
556
COLOR DOPPLER IMAGING OF FNH
JUltrasound Med 11:553-557, 1992
Figure 4 The blood flow signal of the other branch leading in the opposite direction also demonstrates a pulsatile wave form.
of color Doppler devices would greatly facilitate the recognition of tumor-specific flow signals. Recently, attempts to characterize tissue noninvasively with color Doppler flow imaging have been reported by a number of investigators?- 10 They concluded that this technique could be used in the differential diagnosis of hepatic tumors but had only limited value when compared to angiography. However, rapid tmprovement in the devices will soon permit the accurate detection of slower and finer blood flows. To our knowledge, no other report has been published on the characterization of FNH by color Doppler flow imaging. In the present case, centrifugal arterial flow signals originating from the central zone were dearly demonstrated. These signals corresponded ex· actly to the arterial branches seen on sonographic angiography, the most sensitive technique for identi· fying the arteria] vasculature in FNH. 4 ' 11 Besides this case, we observed two other patients with FNH who had undergone surgery who were evaluated by color Doppler flow imaging. In one, with a hepatic nodule 2.5 em in diameter, centrifugal pulsatile flow signals originating from the central zone were also detected by color Doppler flow imaging. Signals corresponding to the centrifugal branches were seen on sonographic
angiography as well. However, no color flow signals were detected in the other patient with FNH and a lesion only 1.0 em in diameter. In our institution, 239 patients with 269 hepatic nodules (184 hepatocellular carcinomas, 36 metastatic liver cancers, 43 hemangiomas, three FNHs, one adenomatous hyperplasia, and three abscesses) have been studied so far by color Doppler imaging using the same equipment. Overall detection rate of color flow signal within the nodule was 65.1% (175/269), and no tumors other than two FNH cases showed the same patterncentrifugal pulsatile flow signals originating from the central zone--on color Doppler imaging. This obser· vation illustrates that color Doppler flow imaging may be useful in distinguishing FNH from malignant vascular tumors when its peculiar arterial vascular pattern is demonstrated. However, further studies are required to confirm the sensitivity and specificity of this finding for the diagnosis of FNH, as only small numbers of FNH were included in this study. Since color Doppler devices are rapidly being improved, we anticipate that the noninvasive characterization of hepatic tumors, including FNH, with color Doppler imaging will be achieved in the near future.
J Ultrasound Med 11:553-557, 1992
REFERENCES 1. Rogers JV, Mack LA, Freeny PC, et al: Hepatic focal nodular hyperplasia: Angiography, CT, sonography, and scintigraphy. AJR 137:983, 1981 2. Fechner RE, Roehm JOF Jr: Angiographic and pathologic correlations of hepatic focal nodular hyperplasia. Am J Surg Pathol1:217, 1977 3. Wanless IR, Mawdsley C, Adams R: On the pathogenesis of focal nodular hyperplasia of the liver. Hepatology 5:1194, 1985 4. Kudo M, Tomita 5, Tochio H, et al: Hepatic focal nodular hyperplasia: Specific findings at dynamic contrast-enhanced US with carbon dioxide microbubbles. Radiology 179:377, 1991 5. Taylor KJW, Ramos I, Morse 55, et al: Focal liver masses: Differential diagnosis with pulsed Doppler US. Radiology 164:643, 1987
KUDO ET AL
557
6. Yasuhara K, Kimura K, Ohto M, et al: Pulsed Doppler in the diagnosis of small liver tumors. Br J Radio) 61:898, 1988 7. Shimamoto K, Sakuma 5, Ishigaki T, et al: Intratumoral blood flow: Evaluation with color Doppler echography. Radiology 165:683, 1987 8. Tanaka 5, Kitamra T, Fujita M, et al: Color Doppler flow imaging of liver tumors. AJR 154:509, 1990 9. Ralls PW, Johnson MB, Lee KP, et al: Color Doppler sonography in hepatocellular carcinoma. Am J Physiol Imaging 6:57, 1991 10. Tanaka S, Kitamra T, Fujita M, et al: Small hepatocellular carcinoma: Differentiation from adenomatous hyperplas· tic nodule with color Doppler flow imaging. Radiology 182:161, 1992 11. Kudo M, Tomita S, Tochio H, et al: Sonography with intraarterial infusion of carbon dioxide microbubbles (sonographic angiography): Value in differential diagnosis of hepatic tumors. AJR 158:65, 1992
Focal nodular hyperplasia (FNH) is a rare benign hy~ pervascular lesion 1 that is a tumor-like condition but is not a true neoplasm, It is sometimes found incidentally, but occasionally symptoms are noted when it is large in size. Although its vascular architecture is character~ istic,u FNH is difficult to demonstrate by noninvasive modalities, such as computed tomography (CT), magnetic resonance (MR) imaging, and abdominal sonography, and sometimes even by angiography." 4 Recently, Doppler sonography,u especially color Doppler imaging, was introduced as a new diagnostic technique capable of characterizing hepatic tumors noninvasively.7-10 However, to our knowledge the appearance of FNH on color Doppler imaging has not been reported previously. We report the findings in one such patient.
CASE REPORT This 50 year old man was referred to our hospital for further evaluation of a hepatic nodule that was detected incidentally during abdominal sonography. The results of blood tests showed normal liver function, and the physical examination findings were normal. A plain sonogram (Fig. lA) revealed a single homogeneous hypoechoic nodule 3.0 em in diameter Received January 13, 1992, from the Division of Gastroenterology, Department of Medidne (M. K ~ S.T., J.M., Y.O .• H.K.. M.H., A.T. ), and Section of Abdominal Ultrasound (K.M., H.T., K.S.), Kobe City General Hospital, Kobe, japan. Reviied manuscript accepted for publication April29, 1992. Address correspondence and reprint requests to M. Kudo,. MD, Division of Gastroenterology, Department of Medidne, Kobe City General Hospital, 4-6, Minatojima-Nakamachi, Chuo-ku, Kobe 650, Japan.
with a clear margin at the subcapsular region in the anteroin~ ferior area of the right lobe of the liver. CT showed a hypodense mass. A CT scan obtained with contrast enhance· ment demonstrated it to be a high-attenuation mass. The focal defect was demonstrated on radiocolloid liver scan. On MR imaging, the lesion was found to be homogeneously hypointense, with an irregular margin on Tl -weighted sequences (spin-echo, 600/15 TR/TE) and inhomogeneously hyperintense on T2-weighted sequences (spin-echo, 2000/ 70) obtained with a superconducting imager operated at 1.5 T (Magnetom, Siemens, Erlangen, Germany). The early ar· terial phase of hepatic angiography revealed a tortuous dilated artery entering the central part of the lesion, but a spokewheel appearance was not present. The capillary phase of angiography revealed the nodule to be hypervascular, with a faint stain. Sonographic angiography4 showed that the arterial supply arose from the center of the nodule 1 to 2 seconds after the infusion of C02 microbubbles (early arterial phase) (Fig. lB, C). The dilated artery observed at the center of the nodule branched toward the periphery, mainly in two directions; toward the transducer and away from it (Fig. 1B, C). The arterial supply gradually radiated to the periphery during the next few seconds. A hypervascular stain was observed 10 seconds after the infusion of col microbubbles (capillary phase) (Fig. 1D), which is diagnostic of FNH. 4 Color Doppler imaging with a Toshiba SSA 270A (Toshiba, Tokyo, Japan) using a 3.75 MHz transducer dearly demonstrated a dilated color flow signal at the center of the nodule together with two branches: one signal approached the transducer while the other signal went in the opposite direction within the lesion (Fig. 2). corresponding exactly to the findings of sonographic angiography. Both signals showed pulsatile ar· terial waveforms on a pulsed Doppler spectral analysis (Figs. 3, 4). Percutaneous liver biopsy under sonographic guidance confirmed the diagnosis of FNH. The hepatocytes were normal, and the bile duct proliferation and connective tissue, which is considered to be fibrous septa radiating to the
© 1992 by the American Institute of Ultrasound in Medicine • J Ultrasound Med 11:553-557, 1992 • 0278-4297/92/$3.50
554
J Ultrasound Med 11:553- 557, 1992
COLOR DOPPLER IMAGING OF FNH
A
B
c
D
Figure 1 A, An intercostal scan of a plain sonogram shows a 3.0 em hypoechoic nodule in the subcapsular region of the right lobe of the liver (arrows). A hyperechoic spot is barely seen at the center of the lesion (a"ow). B, Sonographic angiography shows the dilated artery in the central zone with two branches (arrows) 1 s after the intra-arterial infusion of C02 microbubbles. C, Sonographic angiography 2 s after the infusion shows a gradual centrifugal filling originating in the central zone. D, Sonographic angiography 10 s after the inlu§ion shows hypervascular staining.
Figure 2 A dilated flow signal that enters the central zone of the nodule (a"owheads) and that branches into two blood flow signals (a"ows) is demonstrated on color Doppler flow imaging.
J Ultrasound Med 11:553- 557, 1992
KUDO ET AL 555
Figure 3 The blood flow signal of the branch that approaches the transducer appears as a pulsatile wave form on the pulsed Doppler spectral analysis, suggesting it is an artery.
periphery from the central scar, were observed. During a 2 year follow-up, the nodule remained stable and has not enlarged.
DISCUSSION The peculiar arterial vasculature of FNH demonstrates a feeding artery that enters the central zone, branches peripherally, and supplies the lesion centrifugallyP The study revealed that the branches originate from the central fibrous zone. 2 Although sonography, CT, and MR imaging provide no findings specific to the diagnosis of FNH, FNH can be confirmed angiographically if the distinctive arteriographic centrifugal filling pattern, the so-called spokewheel sign, can be demonstrated.1 •4 However, although this finding is detected angiographically in 57 to 90% of the cases with extensive FNH, 1·4 it becomes more difficult to detect this pattern angiographically in small areas of FNH, espe24 cially when the diameter is less than 3 cm. 1• • Sonographic angiography with the intra-arterial infusion of C02 microbubbles is an imaging technique 4 that combines sonography and angiography. This new
technique permits the accurate evaluation of tumor hemodynamics. Sonographic angiography demonstrates the arterial vascular pattern of FNH as an early central hypervascular supply with centrifugal filling to the periphery and uniform staining at the capillary phase. This finding is highly specific for FNH (sensitivity, 100%; specificity, 100%) and has not been observed in any other benign or malignant tumor. 4 ·u Because the images that are obtained with sonographic angiog· raphy are tomographic images, exactly the same as color Doppler imaging, sonographic angiography can be assumed to be a gold standard in analyzing the origin of the color flow signals. Color Doppler flow imaging, which was originally developed for viewing the heart and large blood ves· sels, provides information on blood flow, including a pulsed Doppler spectral analysis, and provides an image of the tumor on a single sonogram. Thus, it is possible to obtain simultaneously information previously available only with two separate examinations, sonography and angiography. Taylor and colleaguess suggested that Doppler sonography is a useful clinical method for the noninvasive tissue characterization of hepatic tumors, and they predicted that the application
556
COLOR DOPPLER IMAGING OF FNH
JUltrasound Med 11:553-557, 1992
Figure 4 The blood flow signal of the other branch leading in the opposite direction also demonstrates a pulsatile wave form.
of color Doppler devices would greatly facilitate the recognition of tumor-specific flow signals. Recently, attempts to characterize tissue noninvasively with color Doppler flow imaging have been reported by a number of investigators?- 10 They concluded that this technique could be used in the differential diagnosis of hepatic tumors but had only limited value when compared to angiography. However, rapid tmprovement in the devices will soon permit the accurate detection of slower and finer blood flows. To our knowledge, no other report has been published on the characterization of FNH by color Doppler flow imaging. In the present case, centrifugal arterial flow signals originating from the central zone were dearly demonstrated. These signals corresponded ex· actly to the arterial branches seen on sonographic angiography, the most sensitive technique for identi· fying the arteria] vasculature in FNH. 4 ' 11 Besides this case, we observed two other patients with FNH who had undergone surgery who were evaluated by color Doppler flow imaging. In one, with a hepatic nodule 2.5 em in diameter, centrifugal pulsatile flow signals originating from the central zone were also detected by color Doppler flow imaging. Signals corresponding to the centrifugal branches were seen on sonographic
angiography as well. However, no color flow signals were detected in the other patient with FNH and a lesion only 1.0 em in diameter. In our institution, 239 patients with 269 hepatic nodules (184 hepatocellular carcinomas, 36 metastatic liver cancers, 43 hemangiomas, three FNHs, one adenomatous hyperplasia, and three abscesses) have been studied so far by color Doppler imaging using the same equipment. Overall detection rate of color flow signal within the nodule was 65.1% (175/269), and no tumors other than two FNH cases showed the same patterncentrifugal pulsatile flow signals originating from the central zone--on color Doppler imaging. This obser· vation illustrates that color Doppler flow imaging may be useful in distinguishing FNH from malignant vascular tumors when its peculiar arterial vascular pattern is demonstrated. However, further studies are required to confirm the sensitivity and specificity of this finding for the diagnosis of FNH, as only small numbers of FNH were included in this study. Since color Doppler devices are rapidly being improved, we anticipate that the noninvasive characterization of hepatic tumors, including FNH, with color Doppler imaging will be achieved in the near future.
J Ultrasound Med 11:553-557, 1992
REFERENCES 1. Rogers JV, Mack LA, Freeny PC, et al: Hepatic focal nodular hyperplasia: Angiography, CT, sonography, and scintigraphy. AJR 137:983, 1981 2. Fechner RE, Roehm JOF Jr: Angiographic and pathologic correlations of hepatic focal nodular hyperplasia. Am J Surg Pathol1:217, 1977 3. Wanless IR, Mawdsley C, Adams R: On the pathogenesis of focal nodular hyperplasia of the liver. Hepatology 5:1194, 1985 4. Kudo M, Tomita 5, Tochio H, et al: Hepatic focal nodular hyperplasia: Specific findings at dynamic contrast-enhanced US with carbon dioxide microbubbles. Radiology 179:377, 1991 5. Taylor KJW, Ramos I, Morse 55, et al: Focal liver masses: Differential diagnosis with pulsed Doppler US. Radiology 164:643, 1987
KUDO ET AL
557
6. Yasuhara K, Kimura K, Ohto M, et al: Pulsed Doppler in the diagnosis of small liver tumors. Br J Radio) 61:898, 1988 7. Shimamoto K, Sakuma 5, Ishigaki T, et al: Intratumoral blood flow: Evaluation with color Doppler echography. Radiology 165:683, 1987 8. Tanaka 5, Kitamra T, Fujita M, et al: Color Doppler flow imaging of liver tumors. AJR 154:509, 1990 9. Ralls PW, Johnson MB, Lee KP, et al: Color Doppler sonography in hepatocellular carcinoma. Am J Physiol Imaging 6:57, 1991 10. Tanaka S, Kitamra T, Fujita M, et al: Small hepatocellular carcinoma: Differentiation from adenomatous hyperplas· tic nodule with color Doppler flow imaging. Radiology 182:161, 1992 11. Kudo M, Tomita S, Tochio H, et al: Sonography with intraarterial infusion of carbon dioxide microbubbles (sonographic angiography): Value in differential diagnosis of hepatic tumors. AJR 158:65, 1992
