Diffusion-weighted magnetic resonance imaging as a cancer biomarker: consensus and recommendations

Abstract

On May 3, 2008, a National Cancer Institute (NCI)-sponsored open consensus conference was held in Toronto, Ontario, Canada, during the 2008 International Society for Magnetic Resonance in Medicine Meeting. Approximately 100 experts and stakeholders summarized the current understanding of diffusion-weighted magnetic resonance imaging (DW-MRI) and reached consensus on the use of DW-MRI as a cancer imaging biomarker. DW-MRI should be tested as an imaging biomarker in the context of well-defined clinical trials, by adding DW-MRI to existing NCI-sponsored trials, particularly those with tissue sampling or survival indicators. Where possible, DW-MRI measurements should be compared with histologic indices including cellularity and tissue response. There is a need for tissue equivalent diffusivity phantoms; meanwhile, simple fluid-filled phantoms should be used. Monoexponential assessments of apparent diffusion coefficient values should use two b values (>100 and between 500 and 1000 mm2/sec depending on the application). Free breathing with multiple acquisitions is superior to complex gating techniques. Baseline patient reproducibility studies should be part of study designs. Both region of interest and histogram analysis of apparent diffusion coefficient measurements should be obtained. Standards for measurement, analysis, and display are needed. Annotated data from validation studies (along with outcome measures) should be made publicly available. Magnetic resonance imaging vendors should be engaged in this process. The NCI should establish a task force of experts (physicists, radiologists, and oncologists) to plan, organize technical aspects, and conduct pilot trials. The American College of Radiology Imaging Network infrastructure may be suitable for these purposes. There is an extraordinary opportunity for DW-MRI to evolve into a clinically valuable imaging tool, potentially important for drug development.

Figure 1

Restricted diffusion within rectal cancer with extension into the perirectal space. T2-weighted image demonstrate a well-circumscribed lesion in the perirectal space. Diffusion-weighted image obtained at a b value of 750 demonstrates a high signal, and corresponding ADC map demonstrates relatively restricted diffusion within the tumor.

Figure 2

Restricted diffusion within a prostate cancer. T2-weighted scan demonstrates a well-circumscribed tumor in the left peripheral zone. The ADC map demonstrates restricted diffusion within the tumor.

Figure 3

Minimally restricted diffusion in brainstem glioma: Axial T2-weighted image (A) at the level of middle-cerebellar peduncles shows slightly heterogeneous, predominantly hyperintense midline mass without significant surrounding edema. There is associated effacement of the fourth ventricle. Axial isotropic DW image (B) and ADC map (C) demonstrate no significant restricted diffusion. Instead, the ADC map demonstrates increased signal intensity compared with normal brain parenchyma, reflecting increased diffusion of water.

Figure 4

Restricted diffusion in CNS lymphoma: Axial enhanced T1-weighted image (A) of the brain shows a slightly heterogeneously enhancing hyperintense left frontal mass with minimal surrounding edema. Axial isotropic DW image (B) and ADC map (C) demonstrate restricted diffusion, suggestive of increased tumor cellularity.

Figure 5

Metastatic renal cancer. Whole-body DW image demonstrates (left to right). Coronal computed tomographic image, coronal T1-weighted MRI at the same plane of section, DW imaging (b800) demonstrating left chest wall metastasis and the fused ADC and T1-weighted MRI.

Figure 6

Diffusion-weighted MRI used in treatment response monitoring. Top row demonstrates a perirectal mass (arrow) on T2-weighted MRI, ADC, and the b₇₅₀ gradient image in this patient with rectal cancer metastastic to a local lymph node. On chemotherapy, the lesion has decreased in size but also has higher ADC values and corresponding lower signal on the b₇₅₀ image. The changes in ADC may be useful for monitoring response to therapy.