Detection of hepatic tumor perfusion following transcatheter arterial chemoembolization with dynamic susceptibility contrast-enhanced echoplanar imaging

TECHNICAL NOTE

DETECTION OF HEPATIC TUMOR PERFUSION FOLLOWING TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION WITH DYNAMIC SUSCEPTIBILITY CONTRAST-ENHANCED ECHOPLANAR IMAGING JIMMY H. M. CHAN, MSc, EDMUND Y. K. TSUI, FRCR, SAU HAR LUK, FRCR, MING KEUNG YUEN, FRCR, YU KEUNG CHEUNG, FRCR, AND KENNETH P. C. WONG,

The aim of the study was to evaluate the usefulness of the magnetic resonance (MR) perfusion maps in the detection of liver tumor perfusion following transcatheter arterial chemoembolization (TACE). MR dynamic susceptibility contrast-enhanced imaging was performed in 12 patients with 10 confirmed hepatocellular carcinoma and 2 confirmed hepatic metastasis using single-shot echoplanar pulse sequence. Time-intensity curves for all hepatic tumors showed a transient signal drop and the hepatic blood volume (HBV) maps were reconstructed. On the HBV maps, most tumors (80%) demonstrated hyperperfusion before TACE and hypoperfusion following TACE. The site and the degree of residual hyperperfusion within the tumor on the HBV maps correlated well with the areas of hypervascularity on the angiograms. In conclusion, the MR perfusion maps can be a promising technique for detecting the perfusion of the residual tumor tissue following TACE.  Elsevier Science Inc., 1999 KEY WORDS:

MR perfusion; Liver perfusion; Hepatic tumor; Chemoembolization; Hepatic blood volume

From the Department of Diagnostic Radiology, Tuen Mun Hospital, Hong Kong, People’s Republic of China (J.H.M.C., E.Y.K.T., S.H.L., M.K.Y., Y.K.C., K.P.C.W.). Address correspondence to: Mr. Jimmy H. M. Chan, Department of Diagnostic Radiology, Tuen Mun Hospital, Tsing Chung Koon Road, Tuen Mun, N.T., Hong Kong, P.R.C. Fax: (852) 24632551. Received March 12, 1999; accepted April 5, 1999. CLINICAL IMAGING 1999;23:190–194  Elsevier Science Inc., 1999. All rights reserved. 655 Avenue of the Americas, New York, NY 10010

BSc

INTRODUCTION Dynamic susceptibility contrast-enhanced magnetic resonance imaging (DSC-MRI) has recently been used in neuroimaging for the early detection and characterization of cerebral infarction and brain neoplasm (1–5). When a bolus of MR contrast agent passes through the intravascular system, it creates local magnetic susceptibility (T2*) effects which cause a transient signal drop. The degree of the signal drop during the first pass (i.e., perfusion phase) bolus of the contrast agent in the intravascular space is directly proportional to the concentration of contrast agent in the blood and the blood volume. A graph of transient signal drop versus time can be used to compute hemodynamic blood volume map which reflects the microvascularity (capillary level) of the tissue. To our knowledge, there has been only one report of its use in the abdominal region. This paper focused on the quantitative analysis of time-intensity curves as well as the enhancement patterns (6). We report our experience with DSC-MRI to acquire and reconstruct hepatic blood volume (HBV) maps of the livers in patients suffering from either hepatic metastasis or hepatocellular carcinoma. The objective of our study was to evaluate the usefulness of the HBV maps in detecting liver tumor perfusion following transcatheter arterial chemoembolization (TACE). MATERIALS AND METHODS Twelve patients (5 men and 7 women, mean age 58.5 years old) who had a history of liver tumor detected 0899-7071/99/$–see front matter PII S0899-7071(99)00119-9

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by computed tomography (CT) or ultrasonography (US) were referred to our MRI center for MR imaging of the liver. Of the 12 patients, 10 had hepatocellular carcinoma, 1 had liver metastasis from carcinoma of the breast and 1 had metastatic adenocarcinoma of unknown origin. All lesions were histopathologically confirmed by fine needle biopsy prior to MR imaging. From the CT images, the size of the liver tumors were measured, and ranged from 3–10 cm (mean 5.6 cm) in diameter. Three patients had small satellite lesions in addition to the main hepatic tumors and one patient had a tumor thrombus in the main portal vein. MR perfusion imaging was performed 6 hours pre TACE and 24 hours post TACE. Post-TACE angiograms and HBV maps were reviewed by two radiologists who were not involved in performing TACE. All patients were studied using a 1.5-T superconducting whole-body imager with a 23 mT/m maximum gradient strength gradient system (Signa Horizon, Echo-speed, Software version 5.6, General Electric Medical Systems, Milwaukee, WI, USA) and a linearly polarized body coil. Before MR perfusion imaging, spin echo T1-weighted [TR 500 ms, TE 8 ms] and fat-suppressed fast spin echo T2-weighted [TR 2500 ms, TE 102 ms, ETL 16] axial images were acquired. The MR perfusion imaging was performed by the single-shot spin echo version of echo planar (SE-EPI) pulse sequence with the following scan parameters: TR, 2000 ms; TE, 80 ms, number of phases, 50; matrix, 128 3 128; field of view, 40 3 40 cm; slice thickness, 10 mm; inter-slice gap, 2 mm; number of excitation, 1; receiver bandwidth, 6 133 kHz. Flow compensation and phase correct techniques were used to reduce flow artifacts as well as geometric distortion. Using the T2-weighted axial image as the localizer image, 6 to 10 slices, depending on the tumor size, in axial plane were acquired. If there were multiple and peripheral tumors, only the largest tumor would be assessed. The acquisition time was 1 minute 20 seconds. In order to enable the patient to hold his breath, for every 20-second interval, the acquisition was paused for 2 seconds to allow the patient to take a new breath hold and the acquisition immediately re-started. Finally, post-contrast T1weighted spin echo axial images were acquired [TR 700 ms, TE 20 ms] with flow compensation. The acquisition was started 10 seconds before the bolus injection of 20 ml of gadopentetate dimeglumine GD-DTPA (Magnevist, Berlex Laboratories, Wayne, NJ, USA). The injections were performed by an MR compatible power injector system (Spectris, Medrad, USA) using 20-gauge angiographic catheters and the injection rate was 5 ml per second. After acquisition,

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all the base images were transferred to the Advantage Windows workstation (software version 2.0, General Electric Medical Systems) for post-processing and the HBV maps were reconstructed via commercially available software called Functool (General Electric Medical Systems). RESULTS All patients tolerated the examinations well and there were no adverse reactions. Breath-hold was impossible in three patients due to poor general condition and the quality of the MR perfusion images were degraded by respiratory motion artifacts. Prior to TACE, the liver tumors were well demonstrated and appeared hypointense on T1-weighted spin echo images and mildly hyperintense on fat-suppressed T2-weighted fast spin echo images. All lesions displayed heterogeneous and rim enhancement on the T1-weighted post-contrast spin echo images. The HBV maps were successfully reconstructed in all examinations. All tumors demonstrated hyperfusion on the HBV maps except in areas of necrosis. In all cases, the kidneys and the spleens appeared extremely hyperperfused on the HBV maps. The HBV maps and angiograms performed 24 hours following TACE were reviewed and analyzed. All liver tumors remained hypointense on T1-weighted spin echo images and mildly hyperintense on fatsuppressed T2-weighted fast spin echo images. All liver tumors had mild and diffuse enhancement on the T1-weighted post-contrast spin echo images. Most tumors (80%) demonstrated moderately to markedly decrease in perfusion and vascularity on HBV maps and angiograms respectively. The site and the degree of residual hyperperfusion within the tumor on the HBV maps correlated well with the areas of hypervascularity on the angiograms. A patient who had treatment of TACE for liver metastasis is shown in Figure 1A and 1B. The GDDTPA-enhanced images showed heterogeneous enhancement of the lesion (Fig. 1A). The HBV map displayed marked hypoperfusion except at the periphery of the tumor where it was hyperperfused (Fig. 1B). Subsequent biopsies confirmed non-viable tissue in the hypoperfused area and tumor cells in the periphery. The difference in appearance of hepatocellular carcinoma on HBV maps before and after TACE are clearly displayed in Figures 2A–2D. The tumor showed hyperperfusion on the HBV map before TACE (Figure 2A) and the signal versus time curve for the region of interest (ROI 1) drawn at the center of the tumor demonstrated a huge transient fall in signal intensity (Figure 2B). Marked decrease

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FIGURE 1. Images of a 50-year-old woman with liver metastases and has recently undergone TACE. (A) T1weighted (700/20) post-contrast axial image of the liver. The Gadolinium-enhanced image showed heterogeneous enhancement in the tumor. (B) Hepatic blood volume (HBV) map of the liver. The HBV map displayed marked hypoperfusion except the periphery of the tumor. The magnitude of perfusion is indicated by the gray scale: white stands for maximal perfusion and black stands for minimal or no perfusion.

in perfusion was noted in the tumor 24 hours following TACE (Figure 2C) and the signal versus time curve for the region of interest (ROI 2) failed to show a transient fall in signal intensity (Figure 2D). DISCUSSION MR perfusion imaging acquires dynamic images rapidly during a bolus injection of paramagnetic con-

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trast agent. The contrast agent enters the intravascular space during the perfusion phase and causes a drop in signal intensity. At the end of first pass or perfusion phase, the contrast agent distributes rapidly into the extracellular compartment and the signal intensity rises. As the HBV maps are generated from the signal intensity drop during the perfusion phase, the maps show differences in perfusion only. The transient signal drop is due to the shortening of T2 relaxation time of the tissue. The magnitude of signal drop is directly proportional to the change in T2 relaxation rate, D(1/T2). Let the parameter DR 5 D(1/T2). According to the exponential law of T2 decay, and the signal intensity Si(t) of the ith pixel at time t is given by Si(t) 5 Si(0) e2DRi(t)TE and therefore, DRi(t) 5 2ln(Si(t)/Si(0))/TE where Si(0) is the initial (t 5 0) signal intensity of the ith pixel and DRi(t) is the change in T2 relaxation rate of the ith pixel at time t. The time integral of DRi(t) is then carried out pixel by pixel across a user-specified time interval (t1, t2) on the signal-time curve and these data can be used to generate blood volume map. Although MR perfusion imaging has been intensively used in cerebral region to acquire cerebral blood volume (CBV) maps, the results in our study showed that the same technique could be applied in the abdominal region to acquire hepatic blood volume (HBV) maps. On CBV maps, most malignant tumors are hyperperfused resulting from microvessel angiogenesis [7]. Similarly, on HBV maps, malignant tumors such as liver metastasis and hepatocellular carcinoma are hyperperfused. The transient signal drop of the tumor is due to magnetic susceptibility produced by dense contrast agent accumulation within the intravascular space of the tumor. As the perfusion map is generated in accordance with the transient signal drop during perfusion phase, the differences between pre-TACE maps and post-TACE maps are due to perfusion. This can be further demonstrated by the signal-time curves by drawing ROIs at the tumor site on the images acquired before and after TACE. Normal liver has variations in perfusion which are displayed on the HBV maps. It is wellknown that the liver has dual blood supplies from arterial and portal venous systems. In the perfusion phase (first pass), liver tissue that is supplied by the portal venous system may show low signal intensity on the HBV map because it does not yet contain contrast agent. The standard method in evaluating the effectiveness of TACE is arteriography, which aims to detect the perfusion of residual tumor tissue. However, arteriography is an invasive technique and the procedure of arteriography, especially selective or superselective arteriography, is complicated and

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FIGURE 2. Images of a 60-year-old man with hepatocellular carcinoma. (A) The HBV map of the liver before TACE displayed marked hyperperfusion in the tumor. White stands for maximal perfusion and black stands for minimal or no perfusion. (B) A signal–time curve was obtained by drawing ROI at the tumor site on the MR perfusion images acquired before TACE. (C) The HBV map of the liver after TACE displayed marked decrease in perfusion in the tumor. White stands for maximal perfusion and black stands for minimal or no perfusion. (D) A signal–time curve was obtained by drawing ROI at the tumor site on the MR perfusion images acquired after TACE.

tedious. On the other hand, MR perfusion imaging is a simple and noninvasive technique, with an acquisition time of as short as two minutes. There are some weak points in this MR imaging technique. In order to minimize the geometric distortion inherent from the single-shot EPI pulse sequence,

a low matrix size (128 3 128) had to be used, resulting in poor spatial resolution. Liver tumors of less than 2 cm in size were undetected on the HBV maps. As the maximum number of images per scan (e.g., 512) was limited by the hardware of the MR system, the maximum number of slices to be acquired

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was limited. If the tumor was too large or if there were multiple peripheral tumors, there would be insufficient tumor coverage. The acquisition time was relatively too long for all patients to perform breath holding. If the patient failed to hold his breath, the respiratory motion artifacts could render the HBV maps non-diagnosable. For those weak patients who could not hold their breaths, the abdominal movement could be significantly reduced by fastening a pillow upon the patient’s abdomen with a strap. In conclusion, our preliminary results indicate that dynamic susceptibility contrast-enhanced magnetic resonance imaging may prove to be a promising technique for the assessment of the effectiveness of TACE by detecting the perfusion of the residual tumor tissue. Further prospective studies with repeated angiography and MR perfusion imaging performed 6–12 weeks post TACE to evaluate tumor hypovascularity and tumor hypoperfusion would be valuable.

We thank Professor Wilfred C. G. Peh of the Department of Diagnostic Radiology, The University of Hong Kong, for his valuable suggestions and comments.

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