The apparent diffusion coefficient (ADC) of water as measured by diffusion-weighted MRI is sensitive to the cellular microenvironment of tissues.  Increases in the ADC have been ascribed to microscopic cell lysis, cell shrinkage, and increased cell membrane permeability.  The ADC has been shown to be valuable for predicting early response to therapies in a variety of cancers in animal models.

Because breast cancer commonly metastasizes to bone, and because bone lesions are very difficult to study with conventional radiographic methods, we are evaluating the use of ADC as an early predictor of therapeutic response of breast cancer metastases in bone.  Changes in the ADC pre and post treatment are being compareded to time to progression (TTP), a robust and clinically relevant measure of therapeutic response.

Representative coronal images and ADC maps of the pelvic region of a breast cancer patient are shown below. Bone lesions in the iliac crest are circled in Panel A for reference. In conventional T1-weighted imaging, bone lesions appear hypointense compared to the surrounding tissue. In T2-weighted imaging bone lesions appear hyperintense due to the increased concentration and mobility of water. Radial-FSE and SSEPI images are shown in panels C and D, respectively. The radial-FSE image exhibits better registration with the T1 and T2 images. Corresponding ADC maps generated from diffusion-weighted radial-FSE and SSEPI sequences are shown in panels E and F, respectively.

In an initial analysis of breast cancer patients responding to chemotherapy (based on the TTP), the ADC of bone metastases was observed to increase by day 11 after the initiation of chemotherapy.  Alternatively, the ADC of bone metastases in non-responding patients was observed to decrease. Preliminary results suggest that the ADC as measured by diffusion-weighted MRI may be predictive of an early response in breast cancer metastases in bone.

Relevant Publications
Jennings et. al, Early response of prostate carcinoma xenografts to docetaxel chemotherapy monitored with diffusion MRI. Neoplasia 2002
Thielmann et. al, Changes in water mobility measured by diffusion MRI predict response of metastatic breast cancer to chemotherapy. Neoplasia 2004
Sarlls et. al, Isotropic diffusion weighting in radial fast spin-echo magnetic resonance imaging. MRM 2005