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Technical Innovation |
1 Russell H. Morgan Department of Radiology and Radiological Sciences, Johns
Hopkins Hospital, 600 N. Wolfe St., Rm. 100, Baltimore, MD 21287.
2 Department of Pathology, Johns Hopkins Hospital, Baltimore, MD 21287.
Received February 7, 2003;
accepted after revision March 14, 2003.
Address correspondence to I. R. Kamel
(ikamel{at}jhmi.edu).
Introduction
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Chemoembolization Technique
An 18-gauge, single-wall needle was used to access the right common femoral
artery using the Seldinger technique. A 5-French vascular sheath was placed
into the right common femoral artery over a 0.035-inch Glidewire (Terumo
Medical, Somerset, NJ). Under fluoroscopic guidance, a 5-French glide
Simmons-1 catheter (Cordis, Miami, FL) was advanced into the aortic arch,
formed, and then used to select the celiac axis. Over the guidewire, the
catheter was advanced into the desired hepatic artery branch, depending on the
tumor location. A 7.5-mL solution containing 100 mg of cisplatin (Platinol,
Bristol-Myers Squibb, Princeton, NJ), 50 mg of doxorubicin (Adriamycin,
Pharmacia-Upjohn, Kalamazoo, MI), and 10 mg of mitomycin C (Mutamycin C,
Bedford Laboratories, Bedford, OH) in a 1:1 mixture with 7.5 mL of ethiodol,
followed by infusion of 150-250 µm of polyvinyl alcohol particles (Ivalon,
Interventional Therapeutic, Fremont, CA), was administered until stasis was
achieved.
MRI Technique
Patients were scanned using a 1.5-T MRI scanner (CV/i, General Electric
Medical Systems, Milwaukee, WI), and a phased array torso coil. Imaging
protocol consisted of T2-weighted fast spin-echo images (matrix size, 256
x 256; slice thickness, 8 mm; interslice gap, 2 mm; TR/TE, 5000/100;
receive bandwidth, 32 kHz), breath-hold diffusion-weighted echoplanar images
(matrix, 128 x 128; slice thickness, 8 mm; interslice gap, 2 mm; b
value, 500; TR range/TE, 5000-6500/110; receive bandwidth, 64 kHz), and
breath-hold unenhanced and contrast-enhanced (0.1 mmol/kg IV gadodiamide
[Omniscan, Nycomed Amersham, Princeton, NJ]) T1-weighted three-dimensional
fat-suppressed spoiled gradient-echo (matrix, 192 x 160; slice
thickness, 4-6 mm; TE, 1.2; receive bandwidth, 64 kHz; flip angle, 15°)
images in the arterial (20 sec) and portal venous (60 sec) phases.
Image Analysis
MRI processing and apparent diffusion coefficient maps were generated using
a commercially available Advantage Windows workstation (General Electric
Medical Systems). Image evaluation was by consensus of two experienced MRI
radiologists, who were unaware of the findings at pathology. All target
lesions 2 cm or larger were evaluated, because smaller lesions may not be
detected on diffusion-weighted imaging. Parameters evaluated included tumor
signal intensity on T1-, T2-, and diffusion-weighted sequences. The percentage
of estimated tumor necrosis was reported on the basis of the degree of
enhancement on portal venous phase images. Apparent diffusion coefficient maps
were generated from the diffusion-weighted images, and values were recorded by
placing a region of interest over the entire area of the treated mass, as seen
on the axial image with the maximum lesion size. Correlation coefficients were
calculated to compare the percentage of necrosis at pathology with both the
degree of enhancement on gadolinium-enhanced MRI and the apparent diffusion
coefficient values.
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A change in tumor size on cross-sectional imaging has been widely accepted as a guide to clinical decision-making. However, tumor size does not substantially decrease 1-2 months after chemoembolization, when the decision to evaluate for possible repeated treatment is made. Therefore, the traditional assessment of tumor dimension is not useful in assessing response to therapy. In addition, conventional CT and MRI are limited in their ability to provide data to quantify tumor necrosis, which is essential in determining prognosis.
Diffusion-weighted imaging can provide an insight about water composition within a tumor and the degree of tumor viability. Viable tumor cells have intact membranes that restrict water diffusion, whereas necrotic tumors have increased water diffusion due to cell membrane disruption. Namimoto et al. [5] reported that the apparent diffusion coefficients of malignant masses were significantly lower than those of benign masses. Chan et al. [6] used apparent diffusion coefficients to differentiate hepatic abscesses from cystic or necrotic tumors. More recently, Taouli et al. [7] reported that diffusion-weighted imaging could be useful in differentiating benign from malignant hepatic masses. In another study of an animal model of hepatocellular carcinoma, diffusion-weighted imaging clearly distinguished the regions of tumor necrosis from viable tumor [8]. However, the use of apparent diffusion coefficients to distinguish necrotic from viable regions in patients with hepatocellular carcinoma has not been described to our knowledge.
The use of diffusion-weighted sequences in the abdomen is challenging. To reduce motion artifacts, we obtained breath-hold images with a matrix size of 128 x 128. This parameter results in a significantly lower resolution than regular breath-hold T1-weighted images with a matrix size of 512 x 160. Therefore, a region of interest may be defined with reasonable accuracy on apparent diffusion coefficient maps of only large (> 2 cm) lesions that can be readily detected. Diffusion-weighted images may not be suitable for evaluating lesions near the dome of the liver because of magnetic susceptibility effects related to air in the lungs. This is true for all echoplanar sequences and can potentially be reduced if a nonechoplanar sequence is implemented.
Limitations of this study include the small sample size, long duration
between MRI and surgery (
98 days), and selection bias because we included
only patients who had pathologic confirmation of the degree of tumor necrosis.
However, it is difficult to obtain pathologic confirmation in patients who
undergo chemoembolization because most of these patients do not undergo
surgery. In addition, biopsy is rarely performed and may result in sampling
error. The role of diffusion-weighted imaging has been documented in animal
model and our study shows its potential in humans. However, it is unlikely
that diffusion-weighted images will be the sole predictor of tumor viability
after chemoembolization. More likely, a model that also includes other
variables such as T2 signal intensity changes, the degree and pattern of
gadolinium enhancement, and iodized oil distribution on CT will produce a more
powerful predictor of tumor necrosis than individual imaging variables. MRI is
typically performed 4 weeks after therapy, the usual follow-up period, to
decide if an additional cycle is necessary. However, the optimum timing of
imaging to detect tumor necrosis has not been identified.
In conclusion, diffusion-weighted imaging can be used to predict the degree of tumor necrosis of large hepatocellular carcinoma after transarterial chemoembolization and to guide patient management. However, further refinement of the sequence could help in its usefulness for small lesions, particularly near the diaphragm, or in patients who are unable to breath-hold.
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