Comment on ADC reductions in postcontrast breast tumors

Abstract

It was with interest that we read the article by Yuen et al (1) who reported measurable decreases in the apparent diffusion coefficient (ADC) of breast tumors following Gd contrast agent administration. The reduction was largest (34%) in lesions deemed to have particularly high vascularity. The observation of contrast agent-induced ADC reductions, and the mechanisms responsible for this effect, have a bearing on the timing, pre-or postcontrast, and interpretation of diffusion weighted imaging (DWI) in the clinical setting. The authors interpret their findings in terms of an oft-discussed two-compartment model in which two distinct water pools contribute to the overall diffusion coefficient: a perfusion component with a relatively high ''pseudo-diffusion'' coefficient (2-4) and an extravascular component with a slower diffusion coefficient. The suggestion is made that the Gd contrast material results in a ''suppression of microperfusioninduced effect'' as also inferred in some neurological studies of postcontrast ADC changes (2,3). Little evidence was put forward to support this reasoning, however, and we believe such reasoning is at fault for at least two reasons. First, negligible physiological effects of commercial Gd contrast agents suggest that blood perfusion throughout the lesion is the same pre-and postcontrast. Second, extinguishing blood signal from T2 and/or T2* shortening effects would require vascular Gd concentrations far higher than anticipated several min after contrast injection, when the post-DWI experiments appear to have been performed.We propose rather that the Gd contrast alters the local magnetic susceptibilities within specific tissue compartments, which in turn produce background magnetic field gradients that can add to, or detract from, diffusion sensitization gradients and subsequently alter measured diffusion coefficients. This effect has been studied both experimentally and theoretically (5,6). Does et al demonstrated substantial decreases in brain ADC values in a rat model as the magnetic susceptibility of blood was increased with the intravascular contrast agent AMI-227 (5), while Zhong et al provided a theoretical description of how an intravoxel Gaussian distribution of background gradients results in a decrease of the apparent diffusion coefficient (6).We thus propose that the sequestration of Gd contrast material within the interstitial, extracellular space of the breast lesions results in background gradients that reduce ADC values as discussed in Does et al and Zhong et al (5,6). Of course, such an effect would also result in reduced T2* values as demonstrated by Does et al. Unfortunately, though Yuen et al state that the ''. . .T2* effect is negligible. . .,'' none of their data were acquired with T2*-sensitive sequences and apparently the mechanisms relating T2* changes to ADC alterations have not been appreciated in either their work or the previous pre-postcontrast studies in neurological applications (2,3). Additional experimentation is required before definitive conclusi...

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