Apparent diffusion coefficients for evaluation of the response of brain tumors treated by Gamma Knife surgery

Clinical article

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Cellular density is a major factor for change in the apparent diffusion coefficient (ADC). The authors hypothesized that loss of tumor cells after Gamma Knife surgery (GKS) may alter the ADC value and used diffusion weighted MR imaging (DW imaging) to evaluate cellular changes in brain tumors to detect their treatment response and the efficacy of GKS.


In this paper the authors describe a prospective trial involving 86 patients harboring 38 solid or predominantly solid brain metastases, 30 meningiomas, and 24 acoustic neuromas that were treated by GKS. The patients underwent serial MR imaging examinations, including DW imaging, before treatment and at multiple intervals following GKS. Follow-up MR images and clinical outcomes were reviewed at 3-month intervals for metastatic lesions and at 6-month intervals for benign tumors. Apparent diffusion coefficients were calculated from echoplanar DW images, and mean ADC values were compared at each follow-up.


The mean ADC value for all meningiomas was 0.82 ± 0.15 × 10−3 mm2/sec before GKS. The mean ADC value as of the last mean follow-up of 42 months was 1.36 ± 0.19 × 10−3 mm2/sec, a significant increase compared to that before treatment (p < 0.0001). Calcification (p = 0.006) and tumor recurrence (p = 0.025) significantly prevented a rise in the ADC level.

The mean ADC value for all solid acoustic neuromas was 1.06 ± 0.17 × 10−3 mm2/sec before GKS. The mean ADC value as of the last mean follow-up of 36 months was 1.72 ± 0.26 × 10−3 mm2/sec, a significant increase (p = 0.0002) compared with values before GKS. At the last mean MR imaging follow-up there appeared to be tumor enlargement in 3 patients (12.5%); however, since the ADC values in these patients were significantly higher than the preradiosurgery values, the finding was considered to be a sign of radiation necrosis rather than tumor recurrence.

The mean ADC value of metastatic tumors was 1.05 ± 0.12 × 10−3 mm2/sec before GKS. This value rose significantly (p < 0.0001) to 1.64 ± 0.18 × 10−3 mm2/sec after GKS at a mean follow-up of 9.4 months. Magnetic resonance imaging showed that 89% of these tumors had been controlled by GKS. In 2 patients there were enlarged lesions, but the ADC values were the same as pre-GKS levels, and therefore, the lesions were deemed recurrent.


Apparent diffusion coefficient values may be useful in evaluating treatment results before a definitive change in volume is evident on imaging studies. In some patients in whom imaging findings are equivocal, ADC values may also be used to distinguish radiation-induced necrosis from tumor recurrence.

Abbreviations used in this paper: ADC = apparent diffusion coefficient; DW = diffusion weighted; GKS = Gamma Knife surgery; ROI = region of interest.

Article Information

Address correspondence to: Chuan-Fu Huang, M.D., Gamma Knife Center, Chung-Shan Medical University, 110 Chien-Kuo North Road, Section 1, Taichung 402, Taiwan. email:

© AANS, except where prohibited by US copyright law.



  • View in gallery

    A–C: Diffusion weighted MR images demonstrating a meningioma. Mild hyperintensity (ADC 0.80 ± 0.11 × 10−3 mm2/sec) of the tumor is present before GKS (A). Hypointensity is noted at the 6-month follow-up (B) and marked hypointensity at the 6-year follow-up (C). D: An ADC map showing a rise in the tumor ADC to 1.40 ± 0.17 × 10−3 mm2/sec. E and F: Regular MR images. The image obtained before GKS shows a 9.6-cm3 tumor treated with a margin dose of 16 Gy (E). The size of the tumor is unchanged 6 years after treatment (F).

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    A: A CT scan showing a calcified spot inside a meningioma treated with GKS. B and C: Magnetic resonance images revealing tumor volume to be 8 cm3 (ADC 0.79 ± 0.23 × 10−3 mm2/sec) before GKS (B) and no change (ADC 0.86 ± 0.19 × 10−3 mm2/sec) at the 5-year follow-up (C). D: Diffusion weighted image showing the ROI for the ADC value.

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    A: Dose planning image for GKS of a meningioma showing the 50% isodose line, which received 12 Gy. B: Magnetic resonance image depicting tumor regrowth at the 4-year follow-up. C: A DW image showing a previously treated area with a high tumor ADC value (1.56 ± 0.21 × 10−3 mm2/sec) (arrow) and a region of recent tumor growth (arrowhead) with an ADC level that approximated the pre-GKS value (0.85 ± 0.19 × 10−3 mm2/sec).

  • View in gallery

    A and B: Magnetic resonance images showing an acoustic neuroma before GKS (A) and the enlarged tumor at the 3-year follow-up. C: Diffusion weighted image showing the ROI for the ADC calculation. The ADC value remained high (1.36 ± 0.13 × 10−3 mm2/sec).

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    A and B: Magnetic resonance images showing enhanced metastatic lesions at the right frontal lobe before GKS (A) and a well-enhanced lesion that appears enlarged 9 months after GKS, although the ADC value was high. C: A PET scan revealing a cold spot indicative of radiation necrosis of the lesions rather than tumor recurrence at the 9-month follow-up.

  • View in gallery

    A and B: Magnetic resonance images revealing brain metastasis in the posterior fossa pre-GKS (A) and enlarged tumor 9 months post-GKS (B). C: Photomicrograph showing high cellularity of malignant cells after craniotomy and tumor removal. H & E, original magnification × 400.


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