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Peritumoral Brain Regions in Gliomas and Meningiomas: Investigation with Isotropic Diffusion-weighted MR Imaging and Diffusion-Tensor MR Imaging¹

¹ From the Department of Radiology, Duke University Medical Center, Box 3808, Durham, NC 27710 (J.M.P., P. McGraw, A.C.G., D.D.); and Department of Radiology, Drexel University School of Medicine, Philadelphia, Pa (P. Mhatre). Received June 18, 2003; revision requested August 27; final revision received January 12, 2004; accepted February 24. Address correspondence to J.M.P.

	ABSTRACT

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
PURPOSE: To retrospectively measure the diffusion-weighted (DW) imaging characteristics of peritumoral hyperintense white matter (WM) and peritumoral normal-appearing WM, as seen on T2-weighted magnetic resonance (MR) images of infiltrative high-grade gliomas and meningiomas.

MATERIALS AND METHODS: Seventeen patients with biopsy-proved glioma and nine patients with imaging findings consistent with meningioma and an adjacent hyperintense region on T2-weighted MR images were examined with DW and diffusion-tensor MR imaging. Apparent diffusion coefficients (ADCs) were measured on maps generated from isotropic DW images of enhancing tumor, hyperintense regions adjacent to enhancing tumor, normal-appearing WM adjacent to hyperintense regions, and analogous locations in the contralateral WM corresponding to these areas. Fractional anisotropy (FA) was measured in similar locations on maps generated from diffusion-tensor imaging data. Changes in ADC and FA in each type of tissue were compared across tumor types by using a two-sample t test. P < .05 indicated statistical significance.

RESULTS: Mean ADCs in peritumoral hyperintense regions were 1.309 x 10^–3 mm²/sec (mean percentage of 181% of normal WM) for gliomas and 1.427 x 10^–3 mm²/sec (192% of normal value) for meningiomas (no significant difference). Mean ADCs in peritumoral normal-appearing WM were 0.723 x 10^–3 mm²/sec (106% of normal value) for gliomas and 0.743 x 10^–3 mm²/sec (102% of normal value) for meningiomas (no significant difference). Mean FA values in peritumoral hyperintense regions were 0.178 (43% of normal WM value) for gliomas and 0.224 (65% of normal value) for meningiomas (P = .05). Mean FA values for peritumoral normal-appearing WM were 0.375 (83% of normal value) for gliomas and 0.404 (100% of normal value) for meningiomas (P = .01).

CONCLUSION: The difference in FA decreases in peritumoral normal-appearing WM between gliomas and meningiomas was significant, and the difference in FA decreases in peritumoral hyperintense regions between these tumors approached but did not reach significance. These findings may indicate a role for diffusion MR imaging in the detection of tumoral infiltration that is not visible on conventional MR images.

© RSNA, 2004

Index terms: Brain, diffusion, 10.91 • Brain neoplasms, diagnosis, 10.363, 10.366, 10.38 • Brain neoplasms, MR, 10.121411, 10.121416, 10.12143, 10.12144 • Magnetic resonance (MR), diffusion study, 10.12144

	INTRODUCTION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
Conventional (ie, spin-echo) magnetic resonance (MR) imaging of brain neoplasms has a number of limitations, including difficulties in demarcating the exact margins of infiltrative tumors, delineating the exact margins of vasogenic edema, and monitoring early changes after tumor therapy. Diffusion-weighted MR imaging is one potential means of assessing the responses of tumors and of adjacent areas of vasogenic edema to treatment (1). Diffusion-tensor MR imaging is a recently developed form of diffusion-weighted imaging that enables the assessment of water directionality by allowing one to obtain an approximation of the complex diffusional motion of water in living systems (termed the full diffusion tensor) and indirect information about the integrity of white matter (WM) structures.

The use of diffusion-weighted imaging to better characterize enhancing tumors and vasogenic edema has been explored, but the results obtained by using isotropic (ie, three-direction) diffusion-weighted imaging techniques have been conflicting (2–4). Only a few studies of diffusion-tensor imaging of peritumoral hyperintense regions seen on T2-weighted MR images have been performed (5–7). In one study (6), the authors found that mean diffusivity values in regions of vasogenic edema adjacent to high-grade gliomas differed significantly from those in regions of vasogenic edema adjacent to metastases, but fractional anisotropy (FA) values did not. FA is one measurement of the tendency for water molecules to predominantly diffuse in any one direction rather than equally diffuse in all directions. Mean diffusivity is a measure of the magnitude of diffusion that is equal to one-third of the trace of the diffusion tensor. Therefore, the mean diffusivity is mathematically equivalent to the apparent diffusion coefficient (ADC).

High-grade glial neoplasms are intraaxial infiltrating tumors without discrete boundaries at histologic analysis that usually have increased ADCs. A combination of infiltrative tumor and vasogenic edema, as is seen in high-grade glial neoplasms, is expected to produce greater disruption of the WM tracts and lower anisotropy measurements than areas consisting solely of vasogenic edema, as are seen surrounding noninfiltrative meningiomas. In one recent study (6), the investigators observed significant decreases in FA values in hyperintense regions adjacent to intraaxial metastases on T2-weighted MR images, but the decreases in mean FA values in these regions did not differ significantly from those in hyperintense regions adjacent to gliomas.

Because intraaxial metastases might cause tumoral infiltration that is not detected on conventional MR images, we sought to compare FA values in hyperintense regions adjacent to meningiomas with those in hyperintense regions adjacent to gliomas. Our hypothesis was that ADC and FA values in hyperintense regions near gliomas would differ from those in hyperintense regions near meningiomas, but both values in both tumor types would differ significantly from those in the normal WM of the contralateral hemisphere.

Tumoral infiltration into regions adjacent to hyperintense regions near gliomas is well recognized (8,9) and is expected to cause decreased anisotropy values and increased ADCs relative to those in the normal WM. No tumor would be expected to be present outside the region of hyperintense signal on T2-weighted MR images near (typically) noninvasive meningiomas, and anisotropy and ADC values would be expected to be normal. In view of these expected findings, the purpose of our study was to retrospectively measure the diffusion-weighted imaging characteristics of peritumoral hyperintense WM and peritumoral normal-appearing WM, as seen on T2-weighted MR images of infiltrative high-grade gliomas and meningiomas.

	MATERIALS AND METHODS

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
The study was performed with permission from the institutional review board of Duke University Medical Center. The requirement for informed consent was waived. The study population included 17 patients (mean age, 48 years; age range, 35–57 years)—11 men (mean age, 50 years; age range, 35–57 years) and six women (mean age, 47 years; age range, 37–56 years)—with a biopsy-proved diagnosis of grade III or grade IV glioma. Differences in sex and mean age were not statistically significant. Formal testing to compare the observed ratio of male to female patients with use of a P value of .05 as a criterion for statistical significance did not yield a statistically significant result. The number of patients with glioma was chosen to match that in a previous study of ADCs in gliomas (10). Five of the 17 patients in the current study were from that study. The remaining 12 patients were selected in a retrospective manner from a database of patients with brain tumors who underwent MR imaging between January 2000 and May 2001. From our database, we selected the first 17 patients with glioma who met our study entry criteria. The names of these patients were not obtained from a table of randomly assigned numbers.

Four of these 17 patients had nonresected tumors, and 13 had undergone partial resection of the tumor. Of the four patients with nonresected tumors, two had begun chemotherapy only, and it was still ongoing at the time of the imaging examinations, and two had undergone both chemotherapy and radiation therapy, which ended 4–5 months before the imaging examinations. Of the 13 patients who had undergone partial resection, three had undergone radiation therapy only, which ended 3–6 months before the imaging examinations, and 10 had undergone both chemotherapy and radiation therapy. Six of the 10 patients were still undergoing chemotherapy at the time of imaging, and the remaining four patients had finished chemotherapy 4–7 months before undergoing imaging. All 10 patients had completed radiation therapy 3–9 months before undergoing imaging.

The study population also included nine patients (six women, three men; mean age, 53 years; age range, 48–59 years) who had a total of 10 neoplasms that were either suspected of being or proved to be meningiomas. The mean age of the women was 52.6 years (age range, 50–58 years), and the mean age of the men was 53.6 years (age range, 48–59 years). These patients were retrospectively chosen from the same database from which the patients with gliomas were chosen; the first nine patients with meningiomas were selected. The number of meningiomas was determined on the basis of the results of a power analysis performed by our statistician. Lesions were presumed to represent meningiomas if they were deemed to be extraaxial in location, had the typical enhancement characteristics of meningiomas (such as dense enhancement), were unlikely to represent other extraaxial tumors, and were slow growing (as judged at previously performed MR imaging or computed tomography).

All of the meningiomas chosen for the study had adjacent hyperintense areas on T2-weighted MR images, which were presumed to represent vasogenic edema. The sizes of these meningiomas and the degrees of vasogenic edema and mass effect associated with these tumors were similar to those of the gliomas chosen for the study. Although meningiomas are typically noninfiltrative and gliomas are typically infiltrative, we believed that this comparison was valid because the effect of each of these two tumors on adjacent tissue, as seen on conventional MR images, is predominantly a mass effect. Two of the 10 meningiomas were resected, and both were shown to have the typical histologic features of meningiomas and were classified as World Health Organization grade I tumors.

The patients with meningiomas were selected by means of a retrospective review of individuals who had undergone MR imaging during the same period that the patients with glioma had undergone MR imaging and whose MR images showed typical features of meningiomas, such as an enhancing extraaxial mass with mild dural extension. Although the mass effect of both tumor types was difficult to measure accurately, the two tumor groups generally had relatively similar mass effects and amounts of edema.

MR Imaging Data Acquisition
All patients were examined with a 1.5-T clinical MR imaging unit (Signa; GE Medical Systems, Milwaukee, Wis) by using a standard head coil. Isotropic diffusion-weighted MR imaging was performed by using a single-shot spin-echo echo-planar sequence with the following parameters: 12,000/98 (repetition time msec/echo time msec), one signal acquired, 128 x 64 matrix, and diffusion gradient encoding in three directions both with a diffusion-weighting factor, b, of 1,000 sec/mm² and with no diffusion gradient (ie, b = 0).

ADCs were derived from an ADC map constructed at an Advantage Windows workstation (GE Medical Systems) operating with the Functool software program (GE Medical Systems). T1-weighted MR imaging sequences were performed in the transverse plane before and after the administration of 0.1 mmol of gadopentetate dimeglumine (Magnevist; Berlex Laboratories, Wayne, NJ) per kilogram of body weight with the following parameters: 500/11, 22-cm² field of view, 256 (frequency) x 194 (phase) matrix, 5-mm section thickness, 2.5-mm intersection gap, and two signals acquired. T2-weighted MR imaging sequences were performed in the transverse plane by using 2,800/100 and the same parameters that were used to perform the T1-weighted sequences.

Isotropic imaging was followed by diffusion-tensor imaging, in which a single-shot spin-echo echo-planar MR imaging sequence was performed with 12,000/minimum, an inversion time of 2,200 msec, one signal acquired, and a 128 x 64 matrix with diffusion gradient encoding in six directions both with a b of 1,000 sec/mm² and with no diffusion gradient (ie, b = 0 sec/mm²). A total of seven diffusion-weighted images were obtained for each image section, and the images were obtained through the entire brain. The section thickness was 5 mm, and the intersection gap was 2.5 mm. The field of view was 40 x 20 cm, and the matrix size was 128 x 64. The imaging time for the diffusion-tensor sequence was approximately 2 minutes.

In addition to the diffusion-tensor sequence, conventional MR imaging sequences were performed. These included transverse nonenhanced T1-weighted, contrast material–enhanced T1-weighted, and T2-weighted MR imaging sequences. The T2-weighted MR imaging sequence parameters were 2,800/100, a field of view of 22 cm², a matrix size of 256 (frequency direction) x 194 (phase direction), a section thickness of 5 mm, an intersection gap of 2.5 mm, and two signals acquired. The T1-weighted MR imaging sequence parameters were 500/14, a field of view of 22 cm², a matrix size of 256 (frequency direction) x 194 (phase direction), a section thickness of 5 mm, an intersection gap of 2.5 mm, and two signals acquired.

MR Imaging Data Analysis
The raw diffusion-tensor data were transferred to an independent workstation (Advantage Windows) and processed by using the Functool software program and proprietary software. The six independent elements of the diffusion tensor—D_xx, D_yy, D_zz, D_xy, D_xz, and D_yz—were statistically calculated for each voxel by using a previously described method and were based on the following equation:

where b_ij is the component of the ith and jth columns of the diffusion gradient matrix b, A(b) is the resulting echo intensity for a gradient sequence with directions and magnitudes of the diffusion-sensitizing gradients described by the b matrix, A(b = 0) is the echo intensity when b is the zero matrix (ie, with no diffusion gradient), and D_ij is the corresponding component of the diffusion-tensor matrix (11). Once the elements of the diffusion tensor were obtained, the eigenvalues of the diffusion tensor were obtained by means of diagonalization of the tensor matrix. ADCs for each voxel were then calculated from the eigenvalues. FA was chosen as the index of anisotropy because it is rotationally invariant and because FA maps provide good gray matter–white matter distinction and good contrast-to-noise ratios (11–13). It is also the most widely used index of anisotropy that is described in recent literature and that can be compared with data from other investigators. FA represents the anisotropic portion of total diffusion. The following equation is used to calculate the FA:

where E₁, E₂, and E₃ are the three eigenvalues, and d equals (E₁ + E₂ + E₃)/3 (11,12). Values for FA range from 0 to 1, where 0 represents isotropic diffusion and 1 represents extremely anisotropic diffusion. The FA value is unitless because it represents a ratio of diffusion coefficients. FA calculations for each voxel were performed and were displayed as an anisotropy map. A single neuroradiologist (P. McGraw) with 1 year of neuroradiology experience visually and qualitatively inspected the FA maps before quantitative analysis was performed. ADCs were measured on maps constructed from isotropic diffusion-weighted imaging data from the same sites that were used to measure FA values, by comparing the ADC maps and FA maps side by side. The two maps were not coregistered.

To compare anisotropy values in various types of tissue in and near gliomas, uniform ovoid regions of interest (ROIs) ranging in size from 85 to 90 mm² were drawn on FA maps in the following locations: enhancing gliomas in WM; hyperintense regions in WM adjacent to gliomas, as seen on T2-weighted MR images; and normal-appearing WM adjacent to hyperintense regions near gliomas, as seen on T2-weighted MR images. All ROIs were drawn in the WM to avoid the inclusion of markedly decreased FA values in gray matter relative to FA values in WM. The ROIs in gliomas were placed in the central portion of the enhancing region of the tumor. ROIs in peritumoral hyperintense regions and in normal-appearing WM adjacent to hyperintense regions were randomly placed on T2-weighted MR images so that a corresponding mirror image location was available in the normal-appearing contralateral WM. In addition, similar-size ROIs were placed in analogous regions for each of these sites in the WM of the contralateral hemisphere. The same neuroradiologist (P. McGraw) placed all of the ROIs and recorded the ADC and FA values in all cases.

For this study, the area of the glioma was defined as the enhancing region seen on contrast-enhanced T1-weighted MR images. The peritumoral hyperintense region was defined as the hyperintense area seen on T2-weighted MR images that surrounded the region corresponding to the enhancing area seen on the T1-weighted MR images. For measurement of normal-appearing WM, which was adjacent to the peritumoral hyperintense region, an ROI was placed in the normal-appearing WM within 1 cm of a peritumoral hyperintense region. In each case, a similar-size ROI was drawn in the WM in the contralateral hemisphere at an analogous "mirror image" site that corresponded to the ROI in the affected hemisphere, and FA values were measured. Thus, each ROI in enhancing glioma had a counterpart ROI in essentially the same location in the WM in the opposite hemisphere, as did ROIs in peritumoral hyperintense areas and ROIs in normal-appearing WM adjacent to hyperintense areas.

In all cases, the size of the ROI was measured and an ROI of similar size was chosen for the contralateral hemisphere. The location was matched as closely as possible by measuring distances from internal landmarks (eg, the inner table of the skull) on T2-weighted MR images and subsequently comparing WM region morphology on FA maps (explained in the following text).

In the case of meningiomas, which are extraaxial neoplasms, an analogous region in the brain parenchyma needed to be chosen. Because the meningiomas studied in this series typically displaced the brain parenchyma substantially, we were able to place an ROI in the contralateral WM that was close to the same distance from the brain cortex as the center of the meningioma. The FA values in meningiomas were measured against values in the contralateral normal-appearing WM, which served as a reference area for the comparison of FA values in gliomas and normal-appearing WM.

ROIs were drawn semiautomatically by using the Functool software. ROIs in enhancing meningiomas were first drawn on contrast-enhanced T1-weighted MR images and then automatically transferred to superimposed FA and ADC maps by using the Functool software. In a similar manner, ROIs in peritumoral hyperintense WM and in normal-appearing WM adjacent to hyperintense areas were first drawn on T2-weighted MR images and then automatically transferred to the appropriate maps by using the Functool software. The FA values in each of these regions were recorded, and the mean FA and standard deviation (SD) for each type of tissue were derived. The FA value was recorded and expressed as a percentage of the FA value in the corresponding ROI in the opposite hemisphere. Although the data sets were not coregistered, a review of the images obtained in all cases revealed only minor variations in head position between data sets.

The fact that one could not reliably exclude the possibility of nonenhancing infiltrative tumor in regions that were hypointense on contrast-enhanced T1-weighted MR images and hyperintense on T2-weighted MR images (which we presumed to represent peritumoral edema) was prospectively recognized as a limitation of the study. To control for this possibility, a comparison group of patients with hyperintense lesions, depicted on T2-weighted MR images, that were thought to represent solely vasogenic edema (rather than possibly a combination of tumoral infiltration and vasogenic edema) was selected. This comparison group consisted of patients who had meningiomas with a surrounding hyperintense area on T2-weighted MR images that was thought to represent peritumoral edema. The same neuroradiologist (P. McGraw) who placed the glioma ROIs placed ROIs on the MR images obtained in the patients with meningioma in the same three regions that were studied in the patients with glioma—specifically, enhancing tumor, peritumoral hyperintense regions, normal-appearing WM adjacent to the peritumoral hyperintense regions, and contralateral control regions that corresponded to these areas.

Statistical Analyses
For all comparisons between gliomas and meningiomas, the two-sample t test was used for statistical analysis, and for comparisons between a given region and the contralateral control region, a paired t test was used. Comparisons between regions and the corresponding contralateral regions were performed by using paired t tests in which the independence between sides was not assumed. These tests were also performed by using Wilcoxon rank sum and Wilcoxon signed rank tests, the results of which were the same as those of the t tests. Results of the more familiar t tests are presented.

The primary comparisons performed in this study were as follows: (a) diffusion-weighted imaging measurements (ie, FA and ADC) in hyperintense regions adjacent to gliomas compared with these measurements in hyperintense regions adjacent to meningiomas and (b) diffusion-weighted imaging measurements in normal-appearing WM adjacent to hyperintense regions near gliomas compared with these measurements in normal-appearing WM adjacent to hyperintense regions near meningiomas. For these comparisons, Bonferroni corrections were applied.

For secondary comparisons between brain regions and the contralateral control regions, no Bonferroni adjustments were applied. A P value of less than .05, with or without Bonferroni adjustment, was required for statistical significance. Computer software (SAS; SAS Institute, Cary, NC) was used to perform all statistical computations. SD estimates are denoted by "SD," and standard error estimates for sample means are denoted by "SEM" (standard error of the mean).

	RESULTS

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
Comparison of ADCs between Gliomas and Contralateral WM
The mean ADC for enhancing gliomas was 1.135 x 10^–3 mm²/sec (SD, 0.328; SEM, 0.080) compared with a mean ADC of 0.787 x 10^–3 mm²/sec (SD, 0.149; SEM, 0.033) for the analogous region in the contralateral WM (Table). For individual regions, the ADC in the enhancing portion of gliomas was, on average, 155% (range, 105.7%–203.4%) of the value in the analogous region in the contralateral WM. Both the difference between the two mean ADC measurements and the mean percentage change in ADC at individual comparisons were significant (P < .001).

The mean ADC for normal-appearing WM adjacent to hyperintense WM was 0.723 x 10^–3 mm²/sec (SD, 0.040; SEM, 0.009) compared with a mean ADC of 0.683 x 10^–3 mm²/sec (SD, 0.039; SEM, 0.008) for the analogous region in the contralateral WM. For individual regions, the ADC in normal-appearing WM adjacent to an area of hyperintense WM was, on average, 106% (range, 95.4%–116.8%) of the value in the analogous region in the contralateral WM. Both the difference between the two mean ADC measurements and the mean percentage change in ADC at individual comparisons were significant (P = .002).

Comparison of ADCs between Meningiomas and Contralateral WM
The mean ADC for meningiomas was 0.781 x 10^–3 mm²/sec (SD, 0.129; SEM, 0.041) compared with a mean ADC of 0.724 x 10^–3 mm²/sec (SD, 0.058; SEM, 0.018) for the analogous region in the contralateral WM. For individual regions, the ADC in meningiomas was, on average, 107% (range, 90.8%–129.8%) of the value in the analogous region in the contralateral WM. Neither the difference between the two mean ADC measurements nor the mean percentage change in ADC at individual comparisons was significant (P = .067).

The mean ADC for hyperintense WM adjacent to enhancing meningiomas was 1.427 x 10^–3 mm²/sec (SD, 0.184; SEM, 0.058) compared with a mean ADC of 0.732 x 10^–3 mm²/sec (SD, 0.047; SEM, 0.015) for the analogous region in the contralateral WM. For individual regions, the ADC in hyperintense WM adjacent to meningiomas was, on average, 192% (range, 148.8%–233.8%) of the value in the analogous region in the contralateral WM. Both the difference between the two mean ADC measurements and the mean percentage change in ADC at individual comparisons were significant (P < .001).

The mean ADC for normal-appearing WM adjacent to hyperintense WM was 0.743 x 10^–3 mm²/sec (SD, 0.070; SEM, 0.020) compared with a mean ADC of 0.727 x 10^–3 mm²/sec (SD, 0.048; SEM, 0.015) for the analogous region in the contralateral WM. For individual regions, the ADC in normal-appearing WM adjacent to hyperintense WM was, on average, 102% (range, 97.0%–110.1%) of the value in the analogous region in the contralateral WM. Neither the difference between the two mean ADC measurements nor the mean percentage change at individual comparisons was significant (P = .327).

ADCs in Hyperintense Regions Adjacent to Enhancing Tumor: Gliomas versus Meningiomas
The mean ADC for hyperintense WM adjacent to enhancing gliomas was 1.309 x 10^–3 mm²/sec. The mean ADC for hyperintense WM adjacent to enhancing meningiomas was 1.427 x 10^–3 mm²/sec. For individual regions, the ADC in hyperintense WM adjacent to gliomas was, on average, 181% of the value in the contralateral WM, and the ADC in hyperintense WM adjacent to meningiomas was, on average, 192% of the value in the contralateral WM. The difference in these values was not significant (P > .50 with Bonferroni correction).

ADCs in Normal-appearing WM Near Tumors: Gliomas versus Meningiomas
The mean ADC for normal-appearing WM adjacent to hyperintense regions near enhancing gliomas was 0.723 x 10^–3 mm²/sec. The mean ADC for normal-appearing WM adjacent to hyperintense regions near meningiomas was 0.743 x 10^–3 mm²/sec. For individual regions, the ADC in normal-appearing WM adjacent to gliomas was, on average, 106% of the value in the contralateral WM, and the ADC in normal-appearing WM adjacent to meningiomas was, on average, 102% of the value in the contralateral WM. The difference in these values was not significant.

Comparison of FA Values between Gliomas and Contralateral WM
The mean FA value for enhancing tumor was 0.164 (SD, 0.059; SEM, 0.014) compared with a mean FA value of 0.349 (SD, 0.076; SEM, 0.018) for the analogous region in the contralateral WM. For individual tumors, the FA value in enhancing tumor was, on average, 50% (range, 21.5%–96.3%) of the value in the analogous region in the contralateral WM (Fig 1). Both the difference between the two mean FA measurements and the mean percentage change in FA at individual comparisons were significant (P < .001).

View larger version (169K): [in this window] [in a new window] [Download PPT slide]   Figure 1a. ADC and FA measurements in 76-year-old man with biopsy-proved World Health Organization grade IV glioblastoma multiforme that was treated with partial resection followed by radiation therapy. (a) Transverse contrast-enhanced T1-weighted MR image (500/14) shows large enhancing lesion with a central nonenhancing region of necrosis in the left hemisphere. One ROI (ROI 1) is marked in the solid portion of the tumor, and another ROI (ROI 2) is marked at a corresponding site in the contralateral WM. (b) On color-coded FA map, the ROIs in a are superimposed; regions of high anisotropy are depicted in yellow and red, and regions of low anisotropy are depicted in blue. The FA value measured in the contralateral WM (ROI 2) is 0.395, and that measured in the tumor (ROI 1) is 0.123 (31% of value in contralateral WM). On ADC map (not shown), the ADC was 0.85 x 10–3 mm2/sec in the contralateral WM and 1.52 x 10–3 mm2/sec (179% of value in contralateral WM) in the tumor. (c) Transverse intermediate-weighted MR image (2,800/30) shows large peritumoral hyperintense area. This image section was chosen because it shows the largest hyperintense area. One ROI (ROI 1) is marked in the peritumoral hyperintense area for measurement of FA and ADC values, and another ROI (ROI 2) is marked at a corresponding site in the contralateral WM. (d) On color-coded FA map, the ROIs in c are superimposed; regions of high anisotropy are depicted in yellow and red, and regions of low anisotropy are depicted in blue. The FA value measured in the contralateral WM (ROI 2) is 0.460, and that measured in the peritumoral hyperintense region (ROI 1) is 0.260 (57% of value in contralateral WM). On ADC map (not shown), the ADC measured in the contralateral WM was 0.92 x 10–3 mm2/sec, and the ADC measured in the peritumoral hyperintense region was 1.70 x 10–3 mm2/sec (185% of value in contralateral WM). (e) On transverse intermediate-weighted MR image (2,800/30), an ROI (ROI 3) has been placed at a normal-appearing WM site adjacent to a peritumoral hyperintense area, and another ROI (ROI 4) has been placed at a corresponding site in the contralateral WM. (f) On color-coded FA map, the ROIs in e are superimposed; regions of high anisotropy are depicted in yellow and red, and regions of low anisotropy are depicted in blue. The FA value measured in the contralateral WM (ROI 4) is 0.300, and that measured in the normal-appearing WM adjacent to the peritumoral hyperintense area (ROI 3) is 0.270 (90% of value in contralateral WM). This FA decrease is less than the mean FA decrease observed in the peritumoral normal-appearing WM (mean decrease of 17% for glioma population in our study). On ADC map (not shown), the ADC in the contralateral WM was 0.77 x 10–3 mm2/sec, and that in the normal-appearing WM adjacent to the peritumoral hyperintense region was 0.81 x 10–3 mm2/sec (105% of value in contralateral WM).

View larger version (146K): [in this window] [in a new window] [Download PPT slide]   Figure 1b. ADC and FA measurements in 76-year-old man with biopsy-proved World Health Organization grade IV glioblastoma multiforme that was treated with partial resection followed by radiation therapy. (a) Transverse contrast-enhanced T1-weighted MR image (500/14) shows large enhancing lesion with a central nonenhancing region of necrosis in the left hemisphere. One ROI (ROI 1) is marked in the solid portion of the tumor, and another ROI (ROI 2) is marked at a corresponding site in the contralateral WM. (b) On color-coded FA map, the ROIs in a are superimposed; regions of high anisotropy are depicted in yellow and red, and regions of low anisotropy are depicted in blue. The FA value measured in the contralateral WM (ROI 2) is 0.395, and that measured in the tumor (ROI 1) is 0.123 (31% of value in contralateral WM). On ADC map (not shown), the ADC was 0.85 x 10–3 mm2/sec in the contralateral WM and 1.52 x 10–3 mm2/sec (179% of value in contralateral WM) in the tumor. (c) Transverse intermediate-weighted MR image (2,800/30) shows large peritumoral hyperintense area. This image section was chosen because it shows the largest hyperintense area. One ROI (ROI 1) is marked in the peritumoral hyperintense area for measurement of FA and ADC values, and another ROI (ROI 2) is marked at a corresponding site in the contralateral WM. (d) On color-coded FA map, the ROIs in c are superimposed; regions of high anisotropy are depicted in yellow and red, and regions of low anisotropy are depicted in blue. The FA value measured in the contralateral WM (ROI 2) is 0.460, and that measured in the peritumoral hyperintense region (ROI 1) is 0.260 (57% of value in contralateral WM). On ADC map (not shown), the ADC measured in the contralateral WM was 0.92 x 10–3 mm2/sec, and the ADC measured in the peritumoral hyperintense region was 1.70 x 10–3 mm2/sec (185% of value in contralateral WM). (e) On transverse intermediate-weighted MR image (2,800/30), an ROI (ROI 3) has been placed at a normal-appearing WM site adjacent to a peritumoral hyperintense area, and another ROI (ROI 4) has been placed at a corresponding site in the contralateral WM. (f) On color-coded FA map, the ROIs in e are superimposed; regions of high anisotropy are depicted in yellow and red, and regions of low anisotropy are depicted in blue. The FA value measured in the contralateral WM (ROI 4) is 0.300, and that measured in the normal-appearing WM adjacent to the peritumoral hyperintense area (ROI 3) is 0.270 (90% of value in contralateral WM). This FA decrease is less than the mean FA decrease observed in the peritumoral normal-appearing WM (mean decrease of 17% for glioma population in our study). On ADC map (not shown), the ADC in the contralateral WM was 0.77 x 10–3 mm2/sec, and that in the normal-appearing WM adjacent to the peritumoral hyperintense region was 0.81 x 10–3 mm2/sec (105% of value in contralateral WM).

View larger version (127K): [in this window] [in a new window] [Download PPT slide]   Figure 1c. ADC and FA measurements in 76-year-old man with biopsy-proved World Health Organization grade IV glioblastoma multiforme that was treated with partial resection followed by radiation therapy. (a) Transverse contrast-enhanced T1-weighted MR image (500/14) shows large enhancing lesion with a central nonenhancing region of necrosis in the left hemisphere. One ROI (ROI 1) is marked in the solid portion of the tumor, and another ROI (ROI 2) is marked at a corresponding site in the contralateral WM. (b) On color-coded FA map, the ROIs in a are superimposed; regions of high anisotropy are depicted in yellow and red, and regions of low anisotropy are depicted in blue. The FA value measured in the contralateral WM (ROI 2) is 0.395, and that measured in the tumor (ROI 1) is 0.123 (31% of value in contralateral WM). On ADC map (not shown), the ADC was 0.85 x 10–3 mm2/sec in the contralateral WM and 1.52 x 10–3 mm2/sec (179% of value in contralateral WM) in the tumor. (c) Transverse intermediate-weighted MR image (2,800/30) shows large peritumoral hyperintense area. This image section was chosen because it shows the largest hyperintense area. One ROI (ROI 1) is marked in the peritumoral hyperintense area for measurement of FA and ADC values, and another ROI (ROI 2) is marked at a corresponding site in the contralateral WM. (d) On color-coded FA map, the ROIs in c are superimposed; regions of high anisotropy are depicted in yellow and red, and regions of low anisotropy are depicted in blue. The FA value measured in the contralateral WM (ROI 2) is 0.460, and that measured in the peritumoral hyperintense region (ROI 1) is 0.260 (57% of value in contralateral WM). On ADC map (not shown), the ADC measured in the contralateral WM was 0.92 x 10–3 mm2/sec, and the ADC measured in the peritumoral hyperintense region was 1.70 x 10–3 mm2/sec (185% of value in contralateral WM). (e) On transverse intermediate-weighted MR image (2,800/30), an ROI (ROI 3) has been placed at a normal-appearing WM site adjacent to a peritumoral hyperintense area, and another ROI (ROI 4) has been placed at a corresponding site in the contralateral WM. (f) On color-coded FA map, the ROIs in e are superimposed; regions of high anisotropy are depicted in yellow and red, and regions of low anisotropy are depicted in blue. The FA value measured in the contralateral WM (ROI 4) is 0.300, and that measured in the normal-appearing WM adjacent to the peritumoral hyperintense area (ROI 3) is 0.270 (90% of value in contralateral WM). This FA decrease is less than the mean FA decrease observed in the peritumoral normal-appearing WM (mean decrease of 17% for glioma population in our study). On ADC map (not shown), the ADC in the contralateral WM was 0.77 x 10–3 mm2/sec, and that in the normal-appearing WM adjacent to the peritumoral hyperintense region was 0.81 x 10–3 mm2/sec (105% of value in contralateral WM).

View larger version (126K): [in this window] [in a new window] [Download PPT slide]   Figure 1d. ADC and FA measurements in 76-year-old man with biopsy-proved World Health Organization grade IV glioblastoma multiforme that was treated with partial resection followed by radiation therapy. (a) Transverse contrast-enhanced T1-weighted MR image (500/14) shows large enhancing lesion with a central nonenhancing region of necrosis in the left hemisphere. One ROI (ROI 1) is marked in the solid portion of the tumor, and another ROI (ROI 2) is marked at a corresponding site in the contralateral WM. (b) On color-coded FA map, the ROIs in a are superimposed; regions of high anisotropy are depicted in yellow and red, and regions of low anisotropy are depicted in blue. The FA value measured in the contralateral WM (ROI 2) is 0.395, and that measured in the tumor (ROI 1) is 0.123 (31% of value in contralateral WM). On ADC map (not shown), the ADC was 0.85 x 10–3 mm2/sec in the contralateral WM and 1.52 x 10–3 mm2/sec (179% of value in contralateral WM) in the tumor. (c) Transverse intermediate-weighted MR image (2,800/30) shows large peritumoral hyperintense area. This image section was chosen because it shows the largest hyperintense area. One ROI (ROI 1) is marked in the peritumoral hyperintense area for measurement of FA and ADC values, and another ROI (ROI 2) is marked at a corresponding site in the contralateral WM. (d) On color-coded FA map, the ROIs in c are superimposed; regions of high anisotropy are depicted in yellow and red, and regions of low anisotropy are depicted in blue. The FA value measured in the contralateral WM (ROI 2) is 0.460, and that measured in the peritumoral hyperintense region (ROI 1) is 0.260 (57% of value in contralateral WM). On ADC map (not shown), the ADC measured in the contralateral WM was 0.92 x 10–3 mm2/sec, and the ADC measured in the peritumoral hyperintense region was 1.70 x 10–3 mm2/sec (185% of value in contralateral WM). (e) On transverse intermediate-weighted MR image (2,800/30), an ROI (ROI 3) has been placed at a normal-appearing WM site adjacent to a peritumoral hyperintense area, and another ROI (ROI 4) has been placed at a corresponding site in the contralateral WM. (f) On color-coded FA map, the ROIs in e are superimposed; regions of high anisotropy are depicted in yellow and red, and regions of low anisotropy are depicted in blue. The FA value measured in the contralateral WM (ROI 4) is 0.300, and that measured in the normal-appearing WM adjacent to the peritumoral hyperintense area (ROI 3) is 0.270 (90% of value in contralateral WM). This FA decrease is less than the mean FA decrease observed in the peritumoral normal-appearing WM (mean decrease of 17% for glioma population in our study). On ADC map (not shown), the ADC in the contralateral WM was 0.77 x 10–3 mm2/sec, and that in the normal-appearing WM adjacent to the peritumoral hyperintense region was 0.81 x 10–3 mm2/sec (105% of value in contralateral WM).

View larger version (113K): [in this window] [in a new window] [Download PPT slide]   Figure 1e. ADC and FA measurements in 76-year-old man with biopsy-proved World Health Organization grade IV glioblastoma multiforme that was treated with partial resection followed by radiation therapy. (a) Transverse contrast-enhanced T1-weighted MR image (500/14) shows large enhancing lesion with a central nonenhancing region of necrosis in the left hemisphere. One ROI (ROI 1) is marked in the solid portion of the tumor, and another ROI (ROI 2) is marked at a corresponding site in the contralateral WM. (b) On color-coded FA map, the ROIs in a are superimposed; regions of high anisotropy are depicted in yellow and red, and regions of low anisotropy are depicted in blue. The FA value measured in the contralateral WM (ROI 2) is 0.395, and that measured in the tumor (ROI 1) is 0.123 (31% of value in contralateral WM). On ADC map (not shown), the ADC was 0.85 x 10–3 mm2/sec in the contralateral WM and 1.52 x 10–3 mm2/sec (179% of value in contralateral WM) in the tumor. (c) Transverse intermediate-weighted MR image (2,800/30) shows large peritumoral hyperintense area. This image section was chosen because it shows the largest hyperintense area. One ROI (ROI 1) is marked in the peritumoral hyperintense area for measurement of FA and ADC values, and another ROI (ROI 2) is marked at a corresponding site in the contralateral WM. (d) On color-coded FA map, the ROIs in c are superimposed; regions of high anisotropy are depicted in yellow and red, and regions of low anisotropy are depicted in blue. The FA value measured in the contralateral WM (ROI 2) is 0.460, and that measured in the peritumoral hyperintense region (ROI 1) is 0.260 (57% of value in contralateral WM). On ADC map (not shown), the ADC measured in the contralateral WM was 0.92 x 10–3 mm2/sec, and the ADC measured in the peritumoral hyperintense region was 1.70 x 10–3 mm2/sec (185% of value in contralateral WM). (e) On transverse intermediate-weighted MR image (2,800/30), an ROI (ROI 3) has been placed at a normal-appearing WM site adjacent to a peritumoral hyperintense area, and another ROI (ROI 4) has been placed at a corresponding site in the contralateral WM. (f) On color-coded FA map, the ROIs in e are superimposed; regions of high anisotropy are depicted in yellow and red, and regions of low anisotropy are depicted in blue. The FA value measured in the contralateral WM (ROI 4) is 0.300, and that measured in the normal-appearing WM adjacent to the peritumoral hyperintense area (ROI 3) is 0.270 (90% of value in contralateral WM). This FA decrease is less than the mean FA decrease observed in the peritumoral normal-appearing WM (mean decrease of 17% for glioma population in our study). On ADC map (not shown), the ADC in the contralateral WM was 0.77 x 10–3 mm2/sec, and that in the normal-appearing WM adjacent to the peritumoral hyperintense region was 0.81 x 10–3 mm2/sec (105% of value in contralateral WM).

View larger version (121K): [in this window] [in a new window] [Download PPT slide]   Figure 1f. ADC and FA measurements in 76-year-old man with biopsy-proved World Health Organization grade IV glioblastoma multiforme that was treated with partial resection followed by radiation therapy. (a) Transverse contrast-enhanced T1-weighted MR image (500/14) shows large enhancing lesion with a central nonenhancing region of necrosis in the left hemisphere. One ROI (ROI 1) is marked in the solid portion of the tumor, and another ROI (ROI 2) is marked at a corresponding site in the contralateral WM. (b) On color-coded FA map, the ROIs in a are superimposed; regions of high anisotropy are depicted in yellow and red, and regions of low anisotropy are depicted in blue. The FA value measured in the contralateral WM (ROI 2) is 0.395, and that measured in the tumor (ROI 1) is 0.123 (31% of value in contralateral WM). On ADC map (not shown), the ADC was 0.85 x 10–3 mm2/sec in the contralateral WM and 1.52 x 10–3 mm2/sec (179% of value in contralateral WM) in the tumor. (c) Transverse intermediate-weighted MR image (2,800/30) shows large peritumoral hyperintense area. This image section was chosen because it shows the largest hyperintense area. One ROI (ROI 1) is marked in the peritumoral hyperintense area for measurement of FA and ADC values, and another ROI (ROI 2) is marked at a corresponding site in the contralateral WM. (d) On color-coded FA map, the ROIs in c are superimposed; regions of high anisotropy are depicted in yellow and red, and regions of low anisotropy are depicted in blue. The FA value measured in the contralateral WM (ROI 2) is 0.460, and that measured in the peritumoral hyperintense region (ROI 1) is 0.260 (57% of value in contralateral WM). On ADC map (not shown), the ADC measured in the contralateral WM was 0.92 x 10–3 mm2/sec, and the ADC measured in the peritumoral hyperintense region was 1.70 x 10–3 mm2/sec (185% of value in contralateral WM). (e) On transverse intermediate-weighted MR image (2,800/30), an ROI (ROI 3) has been placed at a normal-appearing WM site adjacent to a peritumoral hyperintense area, and another ROI (ROI 4) has been placed at a corresponding site in the contralateral WM. (f) On color-coded FA map, the ROIs in e are superimposed; regions of high anisotropy are depicted in yellow and red, and regions of low anisotropy are depicted in blue. The FA value measured in the contralateral WM (ROI 4) is 0.300, and that measured in the normal-appearing WM adjacent to the peritumoral hyperintense area (ROI 3) is 0.270 (90% of value in contralateral WM). This FA decrease is less than the mean FA decrease observed in the peritumoral normal-appearing WM (mean decrease of 17% for glioma population in our study). On ADC map (not shown), the ADC in the contralateral WM was 0.77 x 10–3 mm2/sec, and that in the normal-appearing WM adjacent to the peritumoral hyperintense region was 0.81 x 10–3 mm2/sec (105% of value in contralateral WM).

The mean FA value for normal-appearing WM adjacent to hyperintense WM was 0.375 (SD, 0.089; SEM, 0.022) compared with a mean FA value of 0.459 (SD: 0.084; SEM, 0.020) for the analogous region in the contralateral WM. For individual regions, the FA value in normal-appearing WM adjacent to hyperintense WM was, on average, 83% (range, 43.2%–104.0%) of the value in the analogous region in the contralateral WM. Both the difference between the two mean FA measurements and the mean percentage change at individual comparisons were significant (P = .004).

Comparison of FA Values between Meningiomas and Contralateral WM
The mean FA for enhancing tumor was 0.282 (SD, 0.136; SEM, 0.043) compared with a mean FA value of 0.385 (SD: 0.100; SE: 0.032) for the analogous region in the contralateral WM. For individual tumors, the FA value in enhancing tumor was, on average, 79% (range, 34.7%–178.8%) of the value in the analogous region in the contralateral WM (Fig 2). Both the difference between the two mean FA measurements and the mean percentage change in FA at individual comparisons approached but did not reach statistical significance (P = .067).

View larger version (150K): [in this window] [in a new window] [Download PPT slide]   Figure 2a. ADC and FA values in various brain regions in 60-year-old woman with meningioma, which was confirmed at surgery. (a) Transverse contrast-enhanced T1-weighted MR image (500/14) shows homogeneously enhancing extraaxial mass in right middle cranial fossa. ROIs have been drawn on the mass (ROI 1) and at a WM site (ROI 2) in the contralateral temporal lobe that is comparable to the location of the ROI in the meningioma. (b) On color-coded FA map, the ROIs in a are superimposed; regions of high anisotropy are depicted in red and yellow, and regions of low anisotropy are depicted in blue. The FA value measured in the contralateral WM (ROI 2) is 0.241, and that measured in the tumor (ROI 1) is 0.201 (83% of value in contralateral WM). On ADC map (not shown) constructed by using the same ROI locations, the ADC measured in the contralateral WM was 0.81 x 10–3 mm2/sec, and that measured in the tumor was 0.91 x 10–3 mm2/sec (112% of value in contralateral WM). (c) Transverse intermediate-weighted MR image (2,800/30) shows peritumoral hyperintense region. An ROI has been placed in the peritumoral hyperintense region (ROI 1), and another ROI has been placed at a corresponding site in the contralateral WM (ROI 2). (d) On FA map, the ROIs in c are superimposed; regions of high anisotropy are depicted in yellow and red, and regions of low anisotropy are depicted in blue. The FA value measured in the contralateral WM (ROI 2) is 0.450, and that measured in the peritumoral hyperintense region (ROI 1) is 0.260 (58% of value in contralateral WM). On ADC map (not shown) constructed by using the same ROI locations, the ADC measured in the contralateral WM was 0.75 x 10–3 mm2/sec, and that measured in the peritumoral hyperintense region was 1.53 x 10–3 mm2/sec (204% of value in contralateral WM). (e) On transverse intermediate-weighted MR image (2,800/30), an ROI (ROI 3) has been placed in the normal-appearing WM adjacent to the peritumoral hyperintense region, and another ROI (ROI 4) has been placed at a corresponding site in the contralateral WM. (f) On FA map, the ROIs in e are superimposed; regions of high anisotropy are depicted in yellow and red, and regions of low anisotropy are depicted in blue. The FA value measured in the contralateral WM (ROI 4) is 0.339, and that measured in the normal-appearing WM adjacent to the peritumoral hyperintense region (ROI 3) is 0.335 (99% of value in contralateral WM). On ADC map (not shown) constructed by using the same ROI locations, the ADC measured in the contralateral WM was 0.79 x 10–3 mm2/sec, and that measured in the normal-appearing WM adjacent to the peritumoral hyperintense region was 0.76 x 10–3 mm2/sec (96% of value in contralateral WM).

View larger version (145K): [in this window] [in a new window] [Download PPT slide]   Figure 2b. ADC and FA values in various brain regions in 60-year-old woman with meningioma, which was confirmed at surgery. (a) Transverse contrast-enhanced T1-weighted MR image (500/14) shows homogeneously enhancing extraaxial mass in right middle cranial fossa. ROIs have been drawn on the mass (ROI 1) and at a WM site (ROI 2) in the contralateral temporal lobe that is comparable to the location of the ROI in the meningioma. (b) On color-coded FA map, the ROIs in a are superimposed; regions of high anisotropy are depicted in red and yellow, and regions of low anisotropy are depicted in blue. The FA value measured in the contralateral WM (ROI 2) is 0.241, and that measured in the tumor (ROI 1) is 0.201 (83% of value in contralateral WM). On ADC map (not shown) constructed by using the same ROI locations, the ADC measured in the contralateral WM was 0.81 x 10–3 mm2/sec, and that measured in the tumor was 0.91 x 10–3 mm2/sec (112% of value in contralateral WM). (c) Transverse intermediate-weighted MR image (2,800/30) shows peritumoral hyperintense region. An ROI has been placed in the peritumoral hyperintense region (ROI 1), and another ROI has been placed at a corresponding site in the contralateral WM (ROI 2). (d) On FA map, the ROIs in c are superimposed; regions of high anisotropy are depicted in yellow and red, and regions of low anisotropy are depicted in blue. The FA value measured in the contralateral WM (ROI 2) is 0.450, and that measured in the peritumoral hyperintense region (ROI 1) is 0.260 (58% of value in contralateral WM). On ADC map (not shown) constructed by using the same ROI locations, the ADC measured in the contralateral WM was 0.75 x 10–3 mm2/sec, and that measured in the peritumoral hyperintense region was 1.53 x 10–3 mm2/sec (204% of value in contralateral WM). (e) On transverse intermediate-weighted MR image (2,800/30), an ROI (ROI 3) has been placed in the normal-appearing WM adjacent to the peritumoral hyperintense region, and another ROI (ROI 4) has been placed at a corresponding site in the contralateral WM. (f) On FA map, the ROIs in e are superimposed; regions of high anisotropy are depicted in yellow and red, and regions of low anisotropy are depicted in blue. The FA value measured in the contralateral WM (ROI 4) is 0.339, and that measured in the normal-appearing WM adjacent to the peritumoral hyperintense region (ROI 3) is 0.335 (99% of value in contralateral WM). On ADC map (not shown) constructed by using the same ROI locations, the ADC measured in the contralateral WM was 0.79 x 10–3 mm2/sec, and that measured in the normal-appearing WM adjacent to the peritumoral hyperintense region was 0.76 x 10–3 mm2/sec (96% of value in contralateral WM).

View larger version (125K): [in this window] [in a new window] [Download PPT slide]   Figure 2c. ADC and FA values in various brain regions in 60-year-old woman with meningioma, which was confirmed at surgery. (a) Transverse contrast-enhanced T1-weighted MR image (500/14) shows homogeneously enhancing extraaxial mass in right middle cranial fossa. ROIs have been drawn on the mass (ROI 1) and at a WM site (ROI 2) in the contralateral temporal lobe that is comparable to the location of the ROI in the meningioma. (b) On color-coded FA map, the ROIs in a are superimposed; regions of high anisotropy are depicted in red and yellow, and regions of low anisotropy are depicted in blue. The FA value measured in the contralateral WM (ROI 2) is 0.241, and that measured in the tumor (ROI 1) is 0.201 (83% of value in contralateral WM). On ADC map (not shown) constructed by using the same ROI locations, the ADC measured in the contralateral WM was 0.81 x 10–3 mm2/sec, and that measured in the tumor was 0.91 x 10–3 mm2/sec (112% of value in contralateral WM). (c) Transverse intermediate-weighted MR image (2,800/30) shows peritumoral hyperintense region. An ROI has been placed in the peritumoral hyperintense region (ROI 1), and another ROI has been placed at a corresponding site in the contralateral WM (ROI 2). (d) On FA map, the ROIs in c are superimposed; regions of high anisotropy are depicted in yellow and red, and regions of low anisotropy are depicted in blue. The FA value measured in the contralateral WM (ROI 2) is 0.450, and that measured in the peritumoral hyperintense region (ROI 1) is 0.260 (58% of value in contralateral WM). On ADC map (not shown) constructed by using the same ROI locations, the ADC measured in the contralateral WM was 0.75 x 10–3 mm2/sec, and that measured in the peritumoral hyperintense region was 1.53 x 10–3 mm2/sec (204% of value in contralateral WM). (e) On transverse intermediate-weighted MR image (2,800/30), an ROI (ROI 3) has been placed in the normal-appearing WM adjacent to the peritumoral hyperintense region, and another ROI (ROI 4) has been placed at a corresponding site in the contralateral WM. (f) On FA map, the ROIs in e are superimposed; regions of high anisotropy are depicted in yellow and red, and regions of low anisotropy are depicted in blue. The FA value measured in the contralateral WM (ROI 4) is 0.339, and that measured in the normal-appearing WM adjacent to the peritumoral hyperintense region (ROI 3) is 0.335 (99% of value in contralateral WM). On ADC map (not shown) constructed by using the same ROI locations, the ADC measured in the contralateral WM was 0.79 x 10–3 mm2/sec, and that measured in the normal-appearing WM adjacent to the peritumoral hyperintense region was 0.76 x 10–3 mm2/sec (96% of value in contralateral WM).

View larger version (141K): [in this window] [in a new window] [Download PPT slide]   Figure 2d. ADC and FA values in various brain regions in 60-year-old woman with meningioma, which was confirmed at surgery. (a) Transverse contrast-enhanced T1-weighted MR image (500/14) shows homogeneously enhancing extraaxial mass in right middle cranial fossa. ROIs have been drawn on the mass (ROI 1) and at a WM site (ROI 2) in the contralateral temporal lobe that is comparable to the location of the ROI in the meningioma. (b) On color-coded FA map, the ROIs in a are superimposed; regions of high anisotropy are depicted in red and yellow, and regions of low anisotropy are depicted in blue. The FA value measured in the contralateral WM (ROI 2) is 0.241, and that measured in the tumor (ROI 1) is 0.201 (83% of value in contralateral WM). On ADC map (not shown) constructed by using the same ROI locations, the ADC measured in the contralateral WM was 0.81 x 10–3 mm2/sec, and that measured in the tumor was 0.91 x 10–3 mm2/sec (112% of value in contralateral WM). (c) Transverse intermediate-weighted MR image (2,800/30) shows peritumoral hyperintense region. An ROI has been placed in the peritumoral hyperintense region (ROI 1), and another ROI has been placed at a corresponding site in the contralateral WM (ROI 2). (d) On FA map, the ROIs in c are superimposed; regions of high anisotropy are depicted in yellow and red, and regions of low anisotropy are depicted in blue. The FA value measured in the contralateral WM (ROI 2) is 0.450, and that measured in the peritumoral hyperintense region (ROI 1) is 0.260 (58% of value in contralateral WM). On ADC map (not shown) constructed by using the same ROI locations, the ADC measured in the contralateral WM was 0.75 x 10–3 mm2/sec, and that measured in the peritumoral hyperintense region was 1.53 x 10–3 mm2/sec (204% of value in contralateral WM). (e) On transverse intermediate-weighted MR image (2,800/30), an ROI (ROI 3) has been placed in the normal-appearing WM adjacent to the peritumoral hyperintense region, and another ROI (ROI 4) has been placed at a corresponding site in the contralateral WM. (f) On FA map, the ROIs in e are superimposed; regions of high anisotropy are depicted in yellow and red, and regions of low anisotropy are depicted in blue. The FA value measured in the contralateral WM (ROI 4) is 0.339, and that measured in the normal-appearing WM adjacent to the peritumoral hyperintense region (ROI 3) is 0.335 (99% of value in contralateral WM). On ADC map (not shown) constructed by using the same ROI locations, the ADC measured in the contralateral WM was 0.79 x 10–3 mm2/sec, and that measured in the normal-appearing WM adjacent to the peritumoral hyperintense region was 0.76 x 10–3 mm2/sec (96% of value in contralateral WM).

View larger version (119K): [in this window] [in a new window] [Download PPT slide]   Figure 2e. ADC and FA values in various brain regions in 60-year-old woman with meningioma, which was confirmed at surgery. (a) Transverse contrast-enhanced T1-weighted MR image (500/14) shows homogeneously enhancing extraaxial mass in right middle cranial fossa. ROIs have been drawn on the mass (ROI 1) and at a WM site (ROI 2) in the contralateral temporal lobe that is comparable to the location of the ROI in the meningioma. (b) On color-coded FA map, the ROIs in a are superimposed; regions of high anisotropy are depicted in red and yellow, and regions of low anisotropy are depicted in blue. The FA value measured in the contralateral WM (ROI 2) is 0.241, and that measured in the tumor (ROI 1) is 0.201 (83% of value in contralateral WM). On ADC map (not shown) constructed by using the same ROI locations, the ADC measured in the contralateral WM was 0.81 x 10–3 mm2/sec, and that measured in the tumor was 0.91 x 10–3 mm2/sec (112% of value in contralateral WM). (c) Transverse intermediate-weighted MR image (2,800/30) shows peritumoral hyperintense region. An ROI has been placed in the peritumoral hyperintense region (ROI 1), and another ROI has been placed at a corresponding site in the contralateral WM (ROI 2). (d) On FA map, the ROIs in c are superimposed; regions of high anisotropy are depicted in yellow and red, and regions of low anisotropy are depicted in blue. The FA value measured in the contralateral WM (ROI 2) is 0.450, and that measured in the peritumoral hyperintense region (ROI 1) is 0.260 (58% of value in contralateral WM). On ADC map (not shown) constructed by using the same ROI locations, the ADC measured in the contralateral WM was 0.75 x 10–3 mm2/sec, and that measured in the peritumoral hyperintense region was 1.53 x 10–3 mm2/sec (204% of value in contralateral WM). (e) On transverse intermediate-weighted MR image (2,800/30), an ROI (ROI 3) has been placed in the normal-appearing WM adjacent to the peritumoral hyperintense region, and another ROI (ROI 4) has been placed at a corresponding site in the contralateral WM. (f) On FA map, the ROIs in e are superimposed; regions of high anisotropy are depicted in yellow and red, and regions of low anisotropy are depicted in blue. The FA value measured in the contralateral WM (ROI 4) is 0.339, and that measured in the normal-appearing WM adjacent to the peritumoral hyperintense region (ROI 3) is 0.335 (99% of value in contralateral WM). On ADC map (not shown) constructed by using the same ROI locations, the ADC measured in the contralateral WM was 0.79 x 10–3 mm2/sec, and that measured in the normal-appearing WM adjacent to the peritumoral hyperintense region was 0.76 x 10–3 mm2/sec (96% of value in contralateral WM).

View larger version (136K): [in this window] [in a new window] [Download PPT slide]   Figure 2f. ADC and FA values in various brain regions in 60-year-old woman with meningioma, which was confirmed at surgery. (a) Transverse contrast-enhanced T1-weighted MR image (500/14) shows homogeneously enhancing extraaxial mass in right middle cranial fossa. ROIs have been drawn on the mass (ROI 1) and at a WM site (ROI 2) in the contralateral temporal lobe that is comparable to the location of the ROI in the meningioma. (b) On color-coded FA map, the ROIs in a are superimposed; regions of high anisotropy are depicted in red and yellow, and regions of low anisotropy are depicted in blue. The FA value measured in the contralateral WM (ROI 2) is 0.241, and that measured in the tumor (ROI 1) is 0.201 (83% of value in contralateral WM). On ADC map (not shown) constructed by using the same ROI locations, the ADC measured in the contralateral WM was 0.81 x 10–3 mm2/sec, and that measured in the tumor was 0.91 x 10–3 mm2/sec (112% of value in contralateral WM). (c) Transverse intermediate-weighted MR image (2,800/30) shows peritumoral hyperintense region. An ROI has been placed in the peritumoral hyperintense region (ROI 1), and another ROI has been placed at a corresponding site in the contralateral WM (ROI 2). (d) On FA map, the ROIs in c are superimposed; regions of high anisotropy are depicted in yellow and red, and regions of low anisotropy are depicted in blue. The FA value measured in the contralateral WM (ROI 2) is 0.450, and that measured in the peritumoral hyperintense region (ROI 1) is 0.260 (58% of value in contralateral WM). On ADC map (not shown) constructed by using the same ROI locations, the ADC measured in the contralateral WM was 0.75 x 10–3 mm2/sec, and that measured in the peritumoral hyperintense region was 1.53 x 10–3 mm2/sec (204% of value in contralateral WM). (e) On transverse intermediate-weighted MR image (2,800/30), an ROI (ROI 3) has been placed in the normal-appearing WM adjacent to the peritumoral hyperintense region, and another ROI (ROI 4) has been placed at a corresponding site in the contralateral WM. (f) On FA map, the ROIs in e are superimposed; regions of high anisotropy are depicted in yellow and red, and regions of low anisotropy are depicted in blue. The FA value measured in the contralateral WM (ROI 4) is 0.339, and that measured in the normal-appearing WM adjacent to the peritumoral hyperintense region (ROI 3) is 0.335 (99% of value in contralateral WM). On ADC map (not shown) constructed by using the same ROI locations, the ADC measured in the contralateral WM was 0.79 x 10–3 mm2/sec, and that measured in the normal-appearing WM adjacent to the peritumoral hyperintense region was 0.76 x 10–3 mm2/sec (96% of value in contralateral WM).

The mean FA for normal-appearing WM adjacent to hyperintense WM was 0.404 (SD, 0.090; SEM, 0.029) compared with a mean FA value of 0.402 (SD, 0.090; SEM, 0.029) for the analogous region in the contralateral WM. For individual regions, the FA value in normal-appearing WM adjacent to hyperintense WM was, on average, 100% (range, 97.6%–108.8%) of the value in the analogous region in the contralateral WM. Neither the difference between the two mean FA measurements nor the mean percentage change in FA at individual comparisons was significant (P > .10).

FA Values in Hyperintense Regions Adjacent to Enhancing Tumor: Gliomas versus Meningiomas
The mean FA for hyperintense WM adjacent to enhancing gliomas was 0.178 compared with a mean FA of 0.224 for hyperintense WM adjacent to meningiomas. For individual regions, the FA value in hyperintense WM adjacent to gliomas was, on average, 43% of the value in the contralateral WM, and the FA value in hyperintense WM adjacent to meningiomas was, on average, 65% of the value in the contralateral WM. The difference in these values closely approached but did not reach statistical significance (P = .05 with Bonferroni correction).

FA Values in Normal-appearing WM Near Enhancing Tumor: Gliomas versus Meningiomas
The mean FA value for normal-appearing WM adjacent to hyperintense regions near enhancing gliomas was 0.375 (SD, 0.089; SEM, 0.022). The mean FA value for normal-appearing WM adjacent to hyperintense regions near meningiomas was 0.404 (SD, 0.090; SEM, 0.029). For individual regions, the FA value in normal-appearing WM adjacent to gliomas was, on average, 83% of the value in the contralateral WM, and the FA value in normal-appearing WM adjacent to meningiomas was, on average, 100% of the value in the contralateral WM. The difference in these values was significant (P = .01 with Bonferroni correction).

	DISCUSSION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
We observed a mean ADC of 0.727 x 10^–3 mm²/sec for the various WM regions studied in the normal hemisphere in our study patients; this value is comparable with the normal values observed in previous studies (4,14). We recognize that, unlike ADCs, anisotropy values differ according to the specific WM site studied (15). For this reason, we did not compare solely mean anisotropy values for each brain region, but rather we also compared the anisotropy values with those in a corresponding region in essentially the same WM location in the opposite hemisphere.

Comparison of ADCs in Various Brain Regions
The ADCs in gliomas were approximately 50% higher than the ADCs in corresponding regions in the contralateral WM. These findings are in accord with those observed in most previous studies (2,4,5,16). As in previous studies (2,4,5,17), in the present study, the ADCs in gliomas (mean, 1.135 x 10^–3 mm²/sec) were relatively similar to those seen in adjacent hyperintense regions (1.309 x 10^–3 mm²/sec). However, to our knowledge, a decrease in the ADC in a meningioma relative to the ADC in the adjacent vasogenic edema has not been previously shown.

ADC increases in hyperintense regions adjacent to enhancing tumors did not differ significantly between gliomas and meningiomas. Thus, with respect to ADCs, values in hyperintense regions adjacent to gliomas did not differ significantly from those in hyperintense regions adjacent to meningiomas. Therefore, with respect to ADCs, our hypothesis was not supported. Mean ADCs in normal-appearing WM regions adjacent to hyperintense regions also did not differ significantly between gliomas and meningiomas; this finding differed from our initial expectation.

Our findings differ from those of a recent study conducted by Lu et al (6), who found that mean diffusivity values in hyperintense regions adjacent to presumably noninfiltrating neoplasms (specifically, metastases) were significantly higher (198% of normal value) than mean diffusivity values in hyperintense regions adjacent to gliomas (158% of normal value). Nonetheless, the magnitude of increases in ADCs in hyperintense regions in our study (mean of 192% of normal values in meningiomas and of 181% of normal values in gliomas) was of a similar magnitude to the differences in mean diffusivity seen in that study. Another difference between these two studies was the larger number of ROIs placed in each hyperintense region in the Lu et al study, which likely resulted in a better sampling of ADCs. Another important difference is that we measured ADCs in normal-appearing WM adjacent to peritumoral hyperintense regions, which was not analyzed in the Lu et al study.

Comparison of Anisotropy Values
Few studies to measure anisotropy values in or surrounding brain tumors have been performed. The investigators in one study (5) found mean anisotropy values of 0.13 in the enhancing tumor core, of 0.17 in edematous brain tissue, and of 0.48 in the contralateral normal-appearing WM, which are similar to the values that we observed in these regions. However, the authors concluded that the differentiation of abnormal tissue from normal tissue—apparently based on differences within individual patients—was possible. However, in their study, differences in mean values between groups of patients, which were determined only by extrapolating data in individual cases, were small and did not enable the differentiation between tumor and vasogenic edema.

The other study (5) differed from our investigation in many ways. First, in that study, ROIs were not placed in areas of normal-appearing WM adjacent to vasogenic edema. Second, no control group of other tumor types was used. Third, a statistical comparison of values for all patients was not performed. Finally, anisotropy values were directly reported rather than expressed as ratios. The method of reporting anisotropy values is important because these measurements differ substantially according to location, a factor that could markedly affect results. Not surprisingly, the conclusions of the two studies differ. According to our findings, diffusion-tensor imaging does not appear to enable a reliable differentiation between tumor and surrounding hyperintense regions on T2-weighted MR images.

In a recently performed study (6), the investigators attempted to use diffusion-tensor imaging to distinguish vasogenic edema adjacent to metastases from vasogenic edema adjacent to infiltrative high-grade gliomas. The investigators did not observe differences in FA values in vasogenic edema between the two tumor types. However, unlike our group, the investigators in that study did not analyze FA values as percentages of values in the contralateral normal-appearing WM. They analyzed FA measurements only as mean values; this approach could lead to the inability to distinguish differences between tumor groups.

The mean FA values in contralateral normal-appearing WM observed in our study were at the lower end of the range of FA values observed by Lu et al (6). This difference in findings emphasizes the location-specific nature of FA values and the importance of not solely comparing mean values, because mean FA measurements can vary widely, depending on whether they are measured in compact WM or noncompact WM regions. In our study, the anisotropy decreases in hyperintense regions adjacent to high-grade gliomas, as depicted on T2-weighted MR images, were much greater than those in hyperintense regions surrounding meningiomas, and this difference closely approached but did not reach statistical significance (P = .05). Although this difference may indicate a greater disruption of WM due to tumor infiltration, it also may be due to other factors or simply to chance.

In this study, we compared anisotropy measurements in regions of normal-appearing WM adjacent to peritumoral hyperintense regions between two tumor types. Significant decreases (P = .004) in anisotropy values in normal-appearing WM adjacent to peritumoral hyperintense regions near gliomas (but not near meningiomas), relative to corresponding regions in contralateral WM, were seen. The difference in anisotropy values between normal-appearing WM near gliomas and normal-appearing WM near meningiomas was significant (P = .1) and lends support to the possibility that tumoral infiltration that is not seen on T2-weighted MR images may be detectable on diffusion-tensor MR images.

Our study had a number of limitations: First, we do not have histologic documentation to confirm that tumor exists in normal-appearing WM near hyperintense regions adjacent to gliomas. Therefore, we cannot definitively state that infiltrative tumor accounts for the decreased anisotropy values in these regions. Second, various therapeutic regimens can influence FA values in normal-appearing WM. For instance, most of our study patients with high-grade gliomas—unlike the patients with meningiomas—underwent chemotherapy, radiation therapy, or both. We cannot exclude the possibility that some of the differences in diffusion measurements between the two tumor groups may have been due to treatment effects. Another limitation was the use of noncontiguous sections in the diffusion-tensor imaging pulse sequence, which, owing to volume-averaging effects, may have influenced FA values. Finally, in most cases, the diagnosis of meningioma was solely presumptive and was based on the presence of imaging appearances, growth patterns, and clinical features typical of this tumor. Therefore, our results would be different if these presumptions were incorrect.

We observed substantial decreases in anisotropy but only mild increases in ADCs in the peritumoral normal-appearing WM near gliomas. Elevated ADCs generally are seen in the presence of increased extracellular water content (6). Because only mild ADC increases were seen, an increase in extracellular water content does not fully explain the decreased FA values that we observed, which are thought to be due to the disruption of myelin sheaths and the disorganization of axons (18). Similar substantial decreases in anisotropy with only mildly elevated ADCs have been observed in patients with multiple sclerosis and indicate that a disruption of myelin sheaths and axons can occur without a substantial increase in extracellular water content (19).

	FOOTNOTES

 
² Current address: Drs Mori, Bean and Brooks, PA, Jacksonville, Fla.

³ Current address: Redwood Regional Medical Group, Santa Rosa, Calif.

Abbreviations: ADC = apparent diffusion coefficient, FA = fractional anisotropy, ROI = region of interest, SD = standard deviation, SEM = standard error of the mean, WM = white matter

Author contributions: Guarantors of integrity of entire study, J.M.P., P. McGraw; study concepts and design, J.M.P., P. McGraw, A.C.G., P. Mhatre; literature research, J.M.P., P. McGraw; clinical studies, J.M.P.; data acquisition, J.M.P., P. McGraw, A.C.G., P. Mhatre; data analysis/interpretation, all authors; statistical analysis, J.M.P., P. McGraw, D.D.; manuscript preparation, definition of intellectual content, editing, revision/review, and final version approval, J.M.P., P. McGraw.

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