MRI developments over recent years have allowed researchers to explore water molecule motion between cells using diffusion-weighted imaging to indirectly measure cellular density within a tissue.
Diffusion has not yet been studied in large enough samples to provide a sound basis for the use of functional biomarkers. Within three to five years, larger studies may well validate parameters extracted by diffusion-weighted imaging (DWI), and diffusion will be used alongside RECIST to routinely assess tumor response.
Traditionally, shrinking was deemed the most definite tumor "response" post-treatment. But now, diffusion imaging measuring the apparent diffusion coefficient (ADC, representing the mm2/sec that water molecules are able to move between cells) may show that intercellular water movement changes after treatment, even if the size of the tumor does not change.
"Using DWI, future treatments can be more personalized and doctors will have more information to decide whether to continue or increase treatment," said Filipe Caseiro-Alves, MD, PhD, head of the imaging department at the University of Coimbra, Portugal, and chair of a special focus session on DWI of the abdomen at the 2010 European Congress of Radiology meeting in Vienna.
Being able to systematically solve problems using diffusion is related to repeatability and standardization of the technique. "Not all vendors approach MRI sequences in the same way, and the results obtained on one machine may be very different on another. A [Siemens Medical Solutions] machine, for example, may not yield the same ADC results as a [GE Healthcare] machine," Dr. Caseiro-Alves said.
Figure 1 — Follow-up MRI study of cirrhotic patient with previous right hepatectomy for hepatocellular carcinoma. Left: Arterial-phase image does not clearly depict tumor in left liver lobe. Right: Two small recurrent hepatocellular carcinoma foci are evident on fused T1/diffusion-weighted image. Images courtesy of Dr. Caseiro-Alves.
An ADC value measurement of 1.0 × 10-3 mm2/sec might indicate metastasis on one machine but mean something different on another machine, making direct extrapolations hard. For standardization to occur, hardware needs to produce identical measurements. Science meanwhile needs to come up with values that signify likelihood of malignancy or benign tissue.
"Without machines yielding the same results, studies cannot be transposable to develop standard measurements. There need to be internal standards for equipment, while radiologists should work to agree on values and protocols through larger clinical studies," he said.
Some standardization has been achieved. In benign lesions, water movement is freer, but in malignant lesions it is more impeded. Therefore, at extreme values it is possible to differentiate between benign and malignant tissue. For example, 0.9 or 1.0 × 10-3 mm2/sec would indicate a greater likelihood of malignancy and 2.5 × 10-3 mm2/sec would favor benign tissue. However, in the middle, there lies a gray area where measurements are indeterminate and liable to vary depending on the type of scanner and the way in which a sequence is obtained.
Moreover, false positives may occur due to lesions appearing to have restricted diffusion in the case of fibrotic benign tumors. Another problem relates to liver patients with hemochromatosis because iron changes the signal received, leading to different visual impressions, and thus interfering with interpretation.
"Because it is not 100% specific, DWI should be interpreted in conjunction with other information from other techniques such as T2-weighted images and contrast enhancement, as well as morphological imaging," he said (see Figure 1).
Current problems in DWI technology, such as low signal-to-noise ratio (SNR) and limited spatial resolution, are likely to be overcome in part through the more widespread use of higher magnetic field strengths, such as 3-tesla, Dr. Caseiro-Alves added.