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Medical Physics Web: Despite a growing volume of studies looking to determine the true proton range in patients, investigations focusing on verifying proton range in the liver in vivo have been limited, due to poor contrast between irradiated and non-irradiated liver tissue. Now, however, thanks to the use of functional MRI and a hepatocyte-specific contrast agent, researchers in the US have developed a verification method that offers high soft-tissue contrast and high spatial resolution (Radiother. Oncol. 106 378).
"Our method provides a tool to approve the correct delivery of treatment or to detect deviations between the planned and delivered dose distribution retrospectively," Yading Yuan, a medical physics resident at Harvard Medical School, told medicalphysicsweb. "Considering that some liver patients need to come back for re-treatment after one year, our technique could also provide physicians with the exact deposited dose in the patients when prescribing their new treatment plans."
The method developed by Yuan and his colleagues at Massachusetts General Hospital and Harvard Medical School relies on the contrast agent Gd-EOB-DTPA. The beauty of the technique lies in the fact that the uptake of Gd-EOB-DTPA is directly related to the liver function loss due to irradiation. So when studying MR images following administration of Gd-EOB-DTPA, a high MR signal intensity shows areas of functioning liver tissue, whereas reduced signal intensity corresponds to an area with reduced liver function.
"This method has many advantages," commented Yuan. "First and foremost, functional MRI with Gd-EOB-DTPA provides high soft-tissue contrast and high spatial resolution. Also, no additional radiation is induced into the normal liver tissue during MRI scans and the use of routine follow-up MRI scans makes this an economical method for proton range verification."
The team studied the routine follow-up MR scans of five patients with metastatic liver cancer treated with 3D conformal proton stereotactic body radiotherapy with two cross-fired fields. The time interval between the end of treatment and the MR scans ranged from 11 to 25 weeks, and in all cases the MR images were obtained 20 minutes after an intravenous injection of Gd-EOB-DTPA.
In order to verify proton range, the researchers determined the relationship between radiation dose and the resulting MR signal intensity. Then, by applying this dose-signal intensity correlation, they were able to explore any proton range differences between the prescribed radiation dose range and the MRI-estimated dose range along each beam direction.
"Our results showed that beam over- and under-shoot were generally on the order of a few millimetres, which is within our proton treatment margin," commented Yuan. "Undershoot was detected for the majority of sampled voxels. For AP/PA beams, the mean difference was –2.18±4.89 mm. For lateral beams, the mean difference was –3.90±5.87 mm."
Following the success of this feasibility study, one new avenue of research for the team is to identify the earliest time at which there is significant contrast between irradiated and non-irradiated liver tissue. "If we could detect an MR signal intensity change during a typical treatment regime of five fractions in 11 days, this would open the door to an immediate assessment of unacceptable discrepancies between planned and detected dose," said Yuan. "We know we can see the effects of radiation two to three months post-treatment, but no data for earlier time points are available in the literature. Joao Seco, Christian Richter and other colleagues are now running a trial to see if similar changes can be seen as early as one or two weeks after the start of treatment."
In addition, Yuan and his colleagues note that MR signal intensity is not the optimal metric to use in their analysis. "Future studies will investigate a more quantitative metric, such as the T1 value of the tissue, to better reflect the physiological changes after irradiation," said Yuan.
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