Detection
of Hepatic Metastases Using Duplex/Color Doppler Sonography
EDWARD LEEN, M.B., CH.B.,* JACQUELINE A. GOLDBERG, M.D.,t JOHN ROBERTSON, PH.D.,4 G. ROY SUTHERLAND, F.R.C.R.,* DAVID M. HEMINGWAY, F.R.C.S.,t TIMOTHY G. COOKE, M.D.,t and COLIN S. MCARDLE, M.D.t
Current imaging modalities are unable to detect small liver metastases because of limited resolution and contrast differentiation. The association between liver metastases and altered liver blood flow has been demonstrated by dynamic scintigraphy, but the clinical feasibility of this test has been questioned. In this study a novel approach to detecting liver metastases was assessed by measurement of liver blood flow using a duplex/color Doppler System. Hepatic arterial and portal venous blood flows were measured in 16 controls, 50 patients with gastrointestinal cancer, and 6 patients with breast cancer. The ratio of hepatic arterial to total liver blood flow (Doppler perfusion index, DPI) and the ratio of hepatic arterial: portal venous blood flow (Doppler flow ratio, DFR) were calculated. The DPI and DFR values of controls and patients with overt liver metastases were clearly separated (p < 0.0001). The results suggest that duplex/color Doppler ultrasound measurement of hepatic perfusion changes may be of value in the detection of liver metastases.
OLORECTAL CARCINOMA IS the second commonest malignancy in the United States, with an estimated 150,000 new cases in 1989.' Data from natural history studies suggest that up to 40% or 60,000 patients eventually develop hepatic metastases.1 Conventional imaging techniques such as computed tomography (CT), ultrasound (US), magnetic resonance imaging (MRI), and scintigraphy are capable of diagnosing overt hepatic metastases, although they are unable to detect small metastases. This is because they are based on tissuetumor contrast and there is a threshold size below which they are unable to discriminate between normal and abnormal tissues. Ideally liver metastases should be diagnosed at an early stage, but conventional imaging techniques continue to be limited by the above factors. It is known that the presence of even small hepatic C
Supported by the Cancer Research Campaign, United Kingdom. Address reprint requests to Jacqueline A. Goldberg, University Department of Surgery, Royal Infirmary, Alexandra Parade, Glasgow G3 1 2ER, United Kingdom. Accepted for publication January 24, 1991.
599
From the Departments of Radiology* and Surgery,t Royal Infirmary, Alexandra Parade, and the West of Scotland Health Boards, Department of Clinical Physics and Bioengineering,f Glasgow, Scotland
metastases may lead to subtle changes in liver blood flow, and it is possible that by monitoring these hemodynamic changes, earlier detection of liver metastases may be feasible. Previous studies have shown that dynamic scintigraphy may be a useful method of detecting the subtle changes in liver blood flow associated with hepatic metastases. Using this technique, a significant increase in the ratio of hepatic arterial to total liver blood flow was demonstrated in a group of patients with overt hepatic metastases by Parkin and his colleagues.2 These workers went on to suggest that the changes in perfusion associated with the presence of tumor could be of value clinically to detect early hepatic metastases.3 Dynamic scintigraphy provides an indirect representation of liver blood flow. Unfortunately the data are difficult to interpret, and the reproducibility of the technique has been questioned. It therefore has not been incorporated into routine clinical practice.6 Recent technical improvements in duplex/color Doppler systems (e.g., increased sensitivity), however, have made it possible to measure blood flow directly. The accuracy of duplex Doppler measurement of blood flow has been demonstrated in studies of animals and patients. i81n contrast to dynamic scintigraphy, duplex/color Doppler US is a more direct method of volume flow measurement, and is therefore likely to be more accurate. It also has the advantage of being noninvasive, independent of hepatic function, and more readily standardized. The aim ofthis study was to evaluate the use of duplex/ color Doppler ultrasound in the detection of hepatic metastases by measuring changes in hepatic perfusion.
600
LEEN AND OTHERS
Methods Seventy-two individuals were studied: 16 control subjects (age range, 23-75 years), 45 patients with colorectal carcinoma, 2 with gastric cancer, 2 with carcinoid, 1 with esophageal carcinoma, and 6 with breast cancer (age range, 33-75 years). Twenty-six of the patients with colorectal carcinoma, both of the carcinoids, and one of the breast cancer patients had overt hepatic metastases. Plain and enhanced (100 mL Ultravist 370) CT examinations of the liver were performed in all patients (General Electric CT 9800 scanner) to estimate the percentage hepatic replacement by tumor. Scanning of 10or 15-mm slice thicknesses in an adjacent slice sequence was undertaken from the dome of the right hemidiaphragm to below the right lobe of liver. The cross-sectional area of the liver, and the metastatic lesions within the liver, were measured in each slice using the in-built computer software by mapping the perimetry of the regions of interest with the "tracker ball." The percentage hepatic replacement was calculated as the sum of the cross-sectional areas of all metastases from all slices, divided by the sum of the cross-sectional areas of all the slices. A Diasonics Spectra scanner (Diasonics Sonotron Ltd., Bedford, UK) consisting of duplex and color Doppler facilities was used to evaluate hepatic perfusion. In the Doppler mode, ultrasound waves were emitted and received by a single 3.5 MHz annular probe at a frequency of 3 MHz with a repetition frequency of 3.7 kHz. It is possible to steer the Doppler beam to any location, and the angle between the axis of the Doppler beam and that of the vessel examined can be measured from the monitor with this system. An angle within the range of 500 to 680 was used for velocity measurement. Spectral analysis to measure the "time-averaged velocity" was performed using fast Fourier transformation, and the Doppler shift signal was displayed on the monitor. The system is equipped with software to compute the time-averaged velocity (time average of the weighted mean of the velocities) from the velocity spectrum automatically after placement of the calipers at the start and end of one or more cardiac cycles. The cross-sectional area of the vessel was measured by mapping the perimetry of the vessel lumen manually with the "tracker ball." After 12 hours of fasting, all the subjects were examined in the supine position with the 3.5-MHz annular probe. A transverse scan of the epigastrium was made to locate the common hepatic artery in its longitudinal axis. The Doppler cursor was placed over the lumen of the common hepatic artery segment as near to the origin as possible, at the point where it first became horizontally straight. The Doppler sample volume and Doppler beam angle were adjusted and the time-averaged velocity were calculated over four cardiac cycles. The cross-sectional area
Ann. Surg. * November 1991
of the artery was measured at the same point by mapping the perimeter of the lumen at right angles to the vessel. The time-averaged cross-sectional area was calculated by taking the mean of areas measured separately over four different cardiac cycles. The same parameters were obtained for the portal vein in a similar manner. Measurements were taken from as near to the origin of the vessel as possible. All measurements were done under respiratory suspension in expiration to allow optimal visualization of the portal vein and to enable a more acute angle to be achieved for Doppler purposes. Each measurement was performed repeatedly until satisfactory spectral patterns were obtained. We have demonstrated that this technique yields consistent and reproducible results.9 We found that the color Doppler facility enabled quicker and more accurate identification of the vessels, easier recognition of variations in arterial anatomy, and more precise correction of the angle between vessel and Doppler beam. Blood flow within the vessels was calculated as the product of the time-averaged velocity of blood within the lumen and the time-averaged cross-sectional area of the vessel. Absolute values of liver blood flow were obtained by using a correction constant (0.82) derived from an in vitro model in which the flow measured by duplex Doppler was correlated with a calibrated flow meter (r = 0.96; p
of Hepatic Metastases Using Duplex/Color Doppler Sonography
EDWARD LEEN, M.B., CH.B.,* JACQUELINE A. GOLDBERG, M.D.,t JOHN ROBERTSON, PH.D.,4 G. ROY SUTHERLAND, F.R.C.R.,* DAVID M. HEMINGWAY, F.R.C.S.,t TIMOTHY G. COOKE, M.D.,t and COLIN S. MCARDLE, M.D.t
Current imaging modalities are unable to detect small liver metastases because of limited resolution and contrast differentiation. The association between liver metastases and altered liver blood flow has been demonstrated by dynamic scintigraphy, but the clinical feasibility of this test has been questioned. In this study a novel approach to detecting liver metastases was assessed by measurement of liver blood flow using a duplex/color Doppler System. Hepatic arterial and portal venous blood flows were measured in 16 controls, 50 patients with gastrointestinal cancer, and 6 patients with breast cancer. The ratio of hepatic arterial to total liver blood flow (Doppler perfusion index, DPI) and the ratio of hepatic arterial: portal venous blood flow (Doppler flow ratio, DFR) were calculated. The DPI and DFR values of controls and patients with overt liver metastases were clearly separated (p < 0.0001). The results suggest that duplex/color Doppler ultrasound measurement of hepatic perfusion changes may be of value in the detection of liver metastases.
OLORECTAL CARCINOMA IS the second commonest malignancy in the United States, with an estimated 150,000 new cases in 1989.' Data from natural history studies suggest that up to 40% or 60,000 patients eventually develop hepatic metastases.1 Conventional imaging techniques such as computed tomography (CT), ultrasound (US), magnetic resonance imaging (MRI), and scintigraphy are capable of diagnosing overt hepatic metastases, although they are unable to detect small metastases. This is because they are based on tissuetumor contrast and there is a threshold size below which they are unable to discriminate between normal and abnormal tissues. Ideally liver metastases should be diagnosed at an early stage, but conventional imaging techniques continue to be limited by the above factors. It is known that the presence of even small hepatic C
Supported by the Cancer Research Campaign, United Kingdom. Address reprint requests to Jacqueline A. Goldberg, University Department of Surgery, Royal Infirmary, Alexandra Parade, Glasgow G3 1 2ER, United Kingdom. Accepted for publication January 24, 1991.
599
From the Departments of Radiology* and Surgery,t Royal Infirmary, Alexandra Parade, and the West of Scotland Health Boards, Department of Clinical Physics and Bioengineering,f Glasgow, Scotland
metastases may lead to subtle changes in liver blood flow, and it is possible that by monitoring these hemodynamic changes, earlier detection of liver metastases may be feasible. Previous studies have shown that dynamic scintigraphy may be a useful method of detecting the subtle changes in liver blood flow associated with hepatic metastases. Using this technique, a significant increase in the ratio of hepatic arterial to total liver blood flow was demonstrated in a group of patients with overt hepatic metastases by Parkin and his colleagues.2 These workers went on to suggest that the changes in perfusion associated with the presence of tumor could be of value clinically to detect early hepatic metastases.3 Dynamic scintigraphy provides an indirect representation of liver blood flow. Unfortunately the data are difficult to interpret, and the reproducibility of the technique has been questioned. It therefore has not been incorporated into routine clinical practice.6 Recent technical improvements in duplex/color Doppler systems (e.g., increased sensitivity), however, have made it possible to measure blood flow directly. The accuracy of duplex Doppler measurement of blood flow has been demonstrated in studies of animals and patients. i81n contrast to dynamic scintigraphy, duplex/color Doppler US is a more direct method of volume flow measurement, and is therefore likely to be more accurate. It also has the advantage of being noninvasive, independent of hepatic function, and more readily standardized. The aim ofthis study was to evaluate the use of duplex/ color Doppler ultrasound in the detection of hepatic metastases by measuring changes in hepatic perfusion.
600
LEEN AND OTHERS
Methods Seventy-two individuals were studied: 16 control subjects (age range, 23-75 years), 45 patients with colorectal carcinoma, 2 with gastric cancer, 2 with carcinoid, 1 with esophageal carcinoma, and 6 with breast cancer (age range, 33-75 years). Twenty-six of the patients with colorectal carcinoma, both of the carcinoids, and one of the breast cancer patients had overt hepatic metastases. Plain and enhanced (100 mL Ultravist 370) CT examinations of the liver were performed in all patients (General Electric CT 9800 scanner) to estimate the percentage hepatic replacement by tumor. Scanning of 10or 15-mm slice thicknesses in an adjacent slice sequence was undertaken from the dome of the right hemidiaphragm to below the right lobe of liver. The cross-sectional area of the liver, and the metastatic lesions within the liver, were measured in each slice using the in-built computer software by mapping the perimetry of the regions of interest with the "tracker ball." The percentage hepatic replacement was calculated as the sum of the cross-sectional areas of all metastases from all slices, divided by the sum of the cross-sectional areas of all the slices. A Diasonics Spectra scanner (Diasonics Sonotron Ltd., Bedford, UK) consisting of duplex and color Doppler facilities was used to evaluate hepatic perfusion. In the Doppler mode, ultrasound waves were emitted and received by a single 3.5 MHz annular probe at a frequency of 3 MHz with a repetition frequency of 3.7 kHz. It is possible to steer the Doppler beam to any location, and the angle between the axis of the Doppler beam and that of the vessel examined can be measured from the monitor with this system. An angle within the range of 500 to 680 was used for velocity measurement. Spectral analysis to measure the "time-averaged velocity" was performed using fast Fourier transformation, and the Doppler shift signal was displayed on the monitor. The system is equipped with software to compute the time-averaged velocity (time average of the weighted mean of the velocities) from the velocity spectrum automatically after placement of the calipers at the start and end of one or more cardiac cycles. The cross-sectional area of the vessel was measured by mapping the perimetry of the vessel lumen manually with the "tracker ball." After 12 hours of fasting, all the subjects were examined in the supine position with the 3.5-MHz annular probe. A transverse scan of the epigastrium was made to locate the common hepatic artery in its longitudinal axis. The Doppler cursor was placed over the lumen of the common hepatic artery segment as near to the origin as possible, at the point where it first became horizontally straight. The Doppler sample volume and Doppler beam angle were adjusted and the time-averaged velocity were calculated over four cardiac cycles. The cross-sectional area
Ann. Surg. * November 1991
of the artery was measured at the same point by mapping the perimeter of the lumen at right angles to the vessel. The time-averaged cross-sectional area was calculated by taking the mean of areas measured separately over four different cardiac cycles. The same parameters were obtained for the portal vein in a similar manner. Measurements were taken from as near to the origin of the vessel as possible. All measurements were done under respiratory suspension in expiration to allow optimal visualization of the portal vein and to enable a more acute angle to be achieved for Doppler purposes. Each measurement was performed repeatedly until satisfactory spectral patterns were obtained. We have demonstrated that this technique yields consistent and reproducible results.9 We found that the color Doppler facility enabled quicker and more accurate identification of the vessels, easier recognition of variations in arterial anatomy, and more precise correction of the angle between vessel and Doppler beam. Blood flow within the vessels was calculated as the product of the time-averaged velocity of blood within the lumen and the time-averaged cross-sectional area of the vessel. Absolute values of liver blood flow were obtained by using a correction constant (0.82) derived from an in vitro model in which the flow measured by duplex Doppler was correlated with a calibrated flow meter (r = 0.96; p
