Diffusion-weighted MR Imaging of Intracerebral Masses: Comparison with Conventional MR Imaging and Histologic Findings

Tadeusz W. Stadnik; Cristo Chaskis; Alex Michotte; Wael M. Shabana; Katrijn van Rompaey; Robert Luypaert; Lubos Budinsky; Vladimir Jellus; Michel Osteaux

Abstract

BACKGROUND AND PURPOSE: The purposes of this study were to find the role of diffusion-weighted MR imaging in characterizing intracerebral masses and to find a correlation, if any, between the different parameters of diffusion-weighted imaging and histologic analysis of tumors. The usefulness of diffusion-weighted imaging and apparent diffusion coefficient (ADC) maps in tumor delineation was evaluated. Contrast with white matter and ADC values for tumor components with available histology were also evaluated.

METHODS: Twenty patients with clinical and routine MR imaging/CT evidence of intracerebral neoplasm were examined with routine MR imaging and echo-planar diffusion-weighted imaging. The routine MR imaging included at least the axial T2-weighted fast spin-echo and axial T1-weighted spin-echo sequences before and after contrast enhancement. The diffusion-weighted imaging included an echo-planar spin-echo sequence with three b values (0, 300, and 1200 s/mm²), sensitizing gradient in the z direction, and calculated ADC maps. The visual comparison of routine MR images with diffusion-weighted images for tumor delineation was performed as was the statistical analysis of quantitative diffusion-weighted imaging parameters with histologic evaluation.

RESULTS: For tumors, the diffusion-weighted images and ADC maps of gliomas were less useful than the T2-weighted spin-echo and contrast-enhanced T1-weighted spin-echo images in definition of tumor boundaries. Additionally, in six cases of gliomas, neither T2-wighted spin-echo nor diffusion-weighted images were able to show a boundary between tumor and edema, which was present on contrast-enhanced T1-weighted and/or perfusion echo-planar images. The ADC values of solid gliomas, metastases, and meningioma were in the same range. In two cases of lymphomas, there was a good contrast with white matter, with strongly reduced ADC values. For infection, the highest contrast on diffusion-weighted images and lowest ADC values were observed in association with inflammatory granuloma and abscess.

CONCLUSION: Contrary to the findings of previous studies, we found no clear advantage of diffusion-weighted echo-planar imaging in the evaluation of tumor extension. The contrast between gliomas, metastases, meningioma, and white matter was generally lower on diffusion-weighted images and ADC maps compared with conventional MR imaging. Unlike gliomas, the two cases of lymphomas showed hyperintense signal on diffusion-weighted images whereas the case of cerebral abscess showed the highest contrast on diffusion-weighted images with very low ADC values. Further study is required to find out whether this may be useful in the differentiation of gliomas and metastasis from lymphoma and abscess.

The high sensitivity and specificity of echo-planar diffusion-weighted imaging in the diagnosis of acute cerebral infarction is widely accepted (1). The reduced diffusion typical of acute stroke is thought to be related to the cytotoxic edema and shrinking of the extracellular space (2, 3). We can hypothesize that diffusion-weighted imaging may enable us to differentiate various tumor components and to distinguish tumoral invasion from normal tissue or edema. This distinction, if possible, would be very important for planning surgical resection, biopsies, and radiation therapy.

Diffusion-weighted MR imaging has been used by some to evaluate intra-axial tumors. Brunberg et al (4) reported that the apparent diffusion coefficient (ADC) values and index of diffusion anisotropy (index of diffusion anisotropy = ADC maximum − ADC minimum/ADC mean) distinguished normal white matter areas from necrosis and cyst formation, edema, and solid enhancing tumor. Tien et al (5) found that areas of enhancing tumor were relatively hyperintense on diffusion-weighted images and that it was possible to distinguish areas of predominantly unenhanced tumor from areas of predominantly peritumoral edema when the abnormality was located in white matter and aligned in the direction of the diffusion-weighted gradient. Krabbe et al (6) reported that ADC values in contrast-enhancing areas within cerebral metastases were statistically significantly higher than the ADC values in contrast-enhancing areas in cases of high grade gliomas.

The purposes of our study were as follows: 1) to compare the capability of conventional MR imaging and diffusion-weighted imaging to delineate components of brain tumor; 2) to evaluate diffusion-weighted images and ADC maps of contrast-enhancing components of tumors; 3) to calculate contrast and ADC values for tumor components confirmed by histology; 4) to find a correlation, if any, between different parameters of diffusion-weighted imaging and histologic analysis of tumors.

Methods

Between August 1996 and February 1998, 20 patients with clinical and routine MR imaging/CT evidence of cerebral masses were examined with routine MR imaging and echo-planar diffusion-weighted imaging on a Siemens Vision 1.5-T imager (Siemens, Erlangen, Germany) (Table 1). The routine MR imaging included an axial T2-weighted fast spin-echo sequence (6000/90 [TR/TE]; signals acquired, one or two; section thickness, 6 mm; echo train length, 23; matrix, 192 × 256 or 230 × 512; field of view, 184 × 205 or 230 × 230 mm) and an axial T1-weighted spin-echo sequence (600/14; signals acquired, two or three; section thickness, 6 mm; matrix, 220 × 256; field of view, 230 × 230 mm) before and after injection of contrast material.

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TABLE 1:

Summary of histologic diagnoses

Between August 1996 and February 1997, the diffusion-weighted imaging included an axial echo-planar spin-echo sequence (800/123; signals acquired, 10; section thickness, 6 mm; matrix, 128 × 200; field of view, 280 × 280 mm; three b values of 0, 300, and 1200 s/mm²; sensitising gradient in the z direction in all cases and occasionally in the x and y directions). δ (duration) and G (amplitude) of the pulsed gradients were 26 ms and 0, 11, and 22 mT/m, respectively. Δ (distance between the leading edges of the two pulsed gradients) was 59.7 ms.

Since February 1997, the previous sequence was implemented with tensor, Eigen values, and anisotropy calculations (800/123; signals acquired, five; section thickness, 6 mm; matrix, 128 × 200; field of view, 280 × 280 mm; three b values of 0, 300, and 1200 s/mm²; sensitising gradients in the z, x, y, zx, zy, and xy directions).

Comparison of Mass Delineation between Conventional MR Imaging and Diffusion-weighted Imaging

Neither contrast-enhanced images nor T2-weighted images can reliably define tumor boundaries. Therefore, the observers were asked to report only if apparent tumor boundaries available on contrast-enhanced T1-weighted spin-echo and fast T2-weighted spin-echo images were better, equally, or less well delineated on diffusion-weighted images and ADC maps. All images were interpreted by two experienced neuroradiologists (T.W.S., W.M.S.). When disagreement arose, a third neuroradiologist (M.O.) adjudicated.

Previous reports (5) suggest that areas of contrast-enhancing tumor were markedly hyperintense on diffusion-weighted images. Therefore, the observers were asked also to report whether enhancing tumor areas were hyper-, iso-, or hypointense on diffusion-weighted images and ADC maps with respect to the underlying white matter.

It is well known that differentiation between tumor invasion and edema is frequently impossible using conventional MR imaging. In such cases (presence of peritumoral or diffuse hyperintensity on T2-weighted spin-echo images without contrast material uptake on T1-weighted spin-echo images) the observers were also asked to report presence or not on diffusion-weighted images and ADC maps of signal intensity variations that may suggest the presence of tumoral invasion (ie, areas with signal intensity similar to that of the histologically proven tumoral components).

Comparison of Quantitative Diffusion-weighted Imaging Parameters with Histologic Evaluation

For nine patients, the biopsy was performed using a stereotactic frame. For 11 patients, the neurosurgeon was asked to perform the biopsies in predefined areas of tumor. The histologic analysis of the biopsies included the evaluation of cellularity, vascularity, endothelial abnormalities, malignity using 4-digit notification (eg, 0 = no, 1 = low, 2 = medium, 3 = high), and volume of extracellular space using 3-digit notification (eg, 1 = small, 2 = medium, 3 = large).

The following diffusion-weighted imaging parameters were calculated for stereotactic biopsy targets or for surgical biopsy areas. Contrast between target/white matter on contrast-enhanced T1-weighted spin-echo and diffusion-weighted images was defined as (signal intensity of target − signal intensity of white matter)/signal intensity of noise. Signal intensity of noise is signal intensity of the region of interest measured outside the skull of the patient. Contrast between target/white matter on ADC maps was defined as (signal intensity of target − signal intensity of white matter)/((signal intensity of target + signal intensity of white matter)/2). ADC values for target and white matter were obtained in the z, x, and y directions and, when available, ADC values of trace and Eigen values were also obtained. ADC values were expressed in 10⁻⁹ m²/s. The regions of interest for the calculation of ADC values for white matter were chosen in the areas of low anisotropy (eg, in frontal or occipital lobes).

The lattice index maps are also available for eight patients (four glioblastomas, one astrocytoma, one granuloma, one meningioma, and one abscess). The lattice index was calculated using a modification of the technique described by Pierpaoli and Basser (7) and provides a scalar measure for the degree of intervoxel anisotropy coherence (ie, the similarity in the anisotropy characteristics of adjacent voxels).

Pearson statistical analysis was used to correlate the histologic evaluation with the imaging parameters. P < .05 was considered to indicate a statistically significant correlation, and P = .05 to .10 was considered to be marginally significant.

Results

Twenty patients (six glioblastomas, four astrocytomas, one pilocytic astrocytoma, two lymphomas, two metastasis, two metastases, two meninigiomas, one infarct, one granuloma, and one abscess) were available for evaluation (Table 1). A comparison of mass delineation between conventional MR imaging and diffusion-weighted imaging is shown in Table 2.

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TABLE 2:

Comparison of fast T2-weighted spin-echo and contrast-enhanced T1-weighted spin-echo with diffusion-weighted echo-planar imaging and ADC maps in delineation of cerebral tumor boundaries (n = 17)*

Glial Tumors

In all cases of glioblastoma (six cases) and astrocytomas (four cases) the diffusion-weighted images were judged to be inferior to the T2-weighted spin-echo and contrast-enhanced T1-weighted spin-echo images in mass delineation. The solid components were frequently heterogeneous and difficult to differentiate from white matter (Fig 1).

fig 1.

Images from the case of a 34-year-old man with a large grade II astrocytoma in the inferior frontal and parietal area. Differentiation between edema and tumor is unclear on all sequences.

A, Fast T2-weighted spin-echo image.

B, Contrast-enhanced T1-weighted spin-echo image. The stereotactic biopsy was performed in the area of faint contrast material uptake (arrow).

C, Diffusion-weighted echo-planar image acquired with x sensitizing gradient.

D, Diffusion-weighted echo-planar image acquired with y sensitizing gradient.

E, Diffusion-weighted echo-planar image acquired with z sensitizing gradient.

F, Tensor ADC map.

G, Lattice index map. The red/yellow areas represent high/medium anisotropy, and the blue/dark blue areas represent lower anisotropy

The calculated ADC maps did a little better than did the diffusion-weighted images. The delineation was judged to be equivalent to that on the T2-weighted spin-echo and/or contrast-enhanced T1-weighted spin-echo images in two of six cases of gliobastomas and in two of four cases of astrocytoma. For the remaining cases of gliomas, the diffusion-weighted images and ADC maps were judged to be inferior to the T2-weighted spin-echo and contrast-enhanced T1-weighted spin-echo images (Fig 2).

fig 2.

Images from the case of a 52-year-old man with a large glioblastoma.

A, Invasion of corpus callosum and of occipitotemporal white matter is recognized on fast T2-weighted spin-echo image.

B, Invasion of corpus callosum and of occipitotemporal white matter is recognized on contrast-enhanced T1-weighted spin-echo image.

C, Invasion of subinsular white matter is clearly recognized only on the perfusion-weighted echo-planar image (arrow).

D, On the diffusion-weighted image, only cystic components of tumor are clearly shown. There is no clear difference between contrast-enhancing tumor (arrowhead) and edema (arrow).

E, On the ADC map, only cystic components of tumor are clearly shown. There is no clear difference between contrast-enhancing tumor (arrowhead) and edema (arrow).

F, Histologic examination (hematoxylin and eosin; original magnification, ×250) shows a medium sized extracellular space and moderate cellularity

Lymphomas

The delineation of lymphomas on diffusion-weighted images was equivalent to that on the T2-weighted spin-echo and/or contrast-enhanced T1-weighted spin-echo imaging in both cases (Fig 3) but was inferior on ADC maps.

fig 2.

fig 3. Images from the case of a 72-year-old woman with a cerebral lymphoma. A, Fast T2-weighted spin-echo image shows lesion to be moderately hyperintense. B, T1-weighted spin-echo image shows strong enhancement of lesion after the administration of contrast material. C, Diffusion-weighted image shows the lymphoma also to be hyperintense. D, ADC values are in the range of 0.55 to 0.6, similar to the values described in association with acute infarction. E, Histologic examination (hematoxylin and eosin; original magnification, ×250) shows high cellularity and small extracellular space, which was significantly associated with reduced ADC values

Meningioma

The delineation of meningioma on diffusion-weighted images and ADC maps was inferior to that on T2-weighted spin-echo and contrast-enhanced T1-weighted spin-echo images.

Metastases

The delineation of metastases on the diffusion-weighted images was inferior to that on the contrast-enhanced T1-weighted spin-echo images in two cases and equivalent to that on the T2-weighted MR images in one case.