High-field MR begins to define parameters of prostate cancer

 Prostate cancer, perhaps more than any other malignant disease process, poses questions that only imaging can answer. MRI has the potential to yield more information about the prostate gland than any other imaging modality. Because of its parametric capabilities, MRI in a single exam can produce high-resolution anatomic imaging with excellent soft-tissue contrast. It also can add spectroscopic information about the function of the tissue to characterize both the aggressiveness and volume of disease. MRI can generate diffusion-weighted images that provide a microstructural picture of intracellular/extracellular water and dynamic contrast-enhanced images that depict development of the microvessels that are necessary for tumors to grow and metastasize.

Characterizing prostate cancer with MRI nevertheless is becoming more difficult now that the disease is being found at a much earlier stage in much smaller volumes.

"Years ago, with just high-resolution anatomic imaging and spectroscopy at 1.5T, we did a pretty good job with the cancers we were detecting at the time, which tended to be larger volume. But we find ourselves at 1.5T not having adequate spatial resolution for spectroscopy, or for functional data with diffusion and perfusion-weighted imaging, to deal with early-stage disease," said Dr. John Kurhanewicz, a professor of radiology at the University of California, San Francisco.

The prostate gland is a very small, highly heterogeneous organ with multiple zones, numerous structures, and varying degrees of metabolism, and it often harbors benign conditions as well as cancer, all of which make it difficult to image.

Although current platforms for 3T imaging of the prostate are not very robust and 1.5T packages do not easily translate to 3T, researchers are turning to high-field scanning because of what its higher signal-to-noise ratio can offer.

Increased SNR allows radiologists to enhance different parts of the scan. It can be used to improve pixel resolution in the same amount of scanning time or get the same pixel resolution in a faster scan.

"Higher spatial resolution will make it easier to see the margins of the tumor and determine if it is deforming the capsule of the gland and is inside or outside of the gland, which is the classic branch point for clinical decision making," said Dr. Dan Cornfeld, an assistant professor in the department of diagnostic radiology at Yale University.

But 3T's greater spatial resolution isn't enough to dramatically increase the sensitivity, specificity, or accuracy of detecting extracapsular disease with T2-weighted images alone, he said. The advantages of increased SNR most likely will come with spectroscopy and diffusion-weighted and dynamic contrast-enhanced imaging.

NEW DEFINITIONS

Individual aspects of MR imaging are beginning to define physiologic, functional, and morphologic parameters of prostate cancer.

T2 relaxation time, for instance, is shortened when disease is present because cancer in the prostate gland replaces normal ductile morphology with more densely packed malignant epithelial cells, which increases the amount of free water. T2 relaxation time, therefore, is a sensitive marker for prostate cancer. It is ideal for estimating tumor volume, because T2-weighted images have the finest spatial resolution and best contrast. However, T2-weighted imaging lacks specificity because other processes, such as prostatitis and stromal proliferation, also cause changes in ductile morphology.

Functional assessment of the prostate, which tracks changes in steady-state concentrations of metabolites within the intracellular and extracellular spaces, is identifying markers not only of the presence of cancer but potentially of its aggressiveness. Building blocks of phospholipid membrane synthesis and degradation, such as choline and ethanolamine-containing metabolites, appear to increase to roughly the same degree as changes in Gleason score. Citric acid and polyamine spermine, which are secretory products of the prostate, decrease in the presence of cancer, perhaps because of a loss of secretory function or an increase in proliferation.

"Imagine this: You have a T2 abnormality and you think it's cancer. You go in and get spectra from the same region of the gland and find choline is up and citrate and polyamines are down in the same voxels. With all this, your confidence level would go up dramatically because all the parameters are saying the same thing," Kurhanewicz said.

A study from Memorial Sloan-Kettering Cancer Center in New York City suggests, in fact, that spectroscopy and imaging data obtained at 1.5T in conjunction with clinical nomograms incrementally improve the identification of localized and indolent disease.

But because spectroscopy has only about 5 to 7 mm voxels on a side, normal tissue dominates the signal, so abnormal spectra from small cancers are difficult to spot. Moreover, at 1.5T, metabolic peaks are not distinct. Creatinine and choline peaks merge together so citrate spectra must be compared to the creatinine/choline pair. With double the SNR, 3T MRI should separate metabolic peaks and make spectroscopy examinations easier to interpret. Higher field strength MRI doubles spatial resolution in the voxels, which should improve ability to detect small volume disease, he said.

The utility of diffusion-weighted imaging, which measures the difference between extracellular and intracellular water, to identify cancer is just beginning to be understood. Recent studies have shown that diffusion-weighted imaging at 1.5T in com¬bination with T2-weighted images improved the detection of cancer within the prostate. Diffusion is, however, an inherently low-SNR sequence. Theoretically, by getting more signal with 3T, scans should give sequences a sort of jump start and increase resolution, Cornfeld said.

DYNAMIC IMAGING

Dynamic contrast-enhanced imaging, which observes the path of gadolinium as it passes into and out of blood vessels, may be an important tool in the prostate just as it is in the breast, now that studies are indicating that magnitude of uptake and speed of wash-out may be related to the aggressiveness of a cancer.

Diffusion-weighted imaging improved the sensitivity and positive predictive value for finding cancer in 68 prostate tumors when added to T2-weighting at 3T. The technique also distinguished benign from malignant disease in the peripheral and transitional zones in one study from Samsung Medical Center in Seoul.

Other published studies hint at the benefits of combining dynamic contrast enhancement with high-resolution T2 weighting, spectroscopy, and diffusion-weighted imaging. The combination of T2 mapping, diffusion weighting, and dynamic contrast MRI at 3T improved the differentiation of prostate cancer in both the transitional and peripheral zones in a study from Ohio State University.

The challenge is how to utilize data from these advanced techniques to make decisions for individual patients. "It's intriguing that in some individuals, the diffusion and spectroscopy really nail it, and in others the dynamic contrast nails it. At least at this time, there are different imaging combinations that give you the best answer," Kurhanewicz said.

Ms. Sandrick is a contributing editor to Diagnostic Imaging.