MRI characterization of cobalt dichloride-N-acetyl cysteine (C4) contrast agent marker for prostate brachytherapy

Abstract

Brachytherapy, a radiotherapy technique for treating prostate cancer, involves the implantation of numerous radioactive seeds into the prostate. While the implanted seeds can be easily identified on a CT image, distinguishing the prostate and surrounding soft tissues is not as straightforward. Magnetic Resonance Imaging (MRI) offers superior anatomical delineation, but the seeds appear as dark voids and are difficult to identify, thus creating a conundrum. Cobalt dichloride-N-acetyl-cysteine (C4) has previously been shown to be promising as an encapsulated contrast agent marker. We performed spin-lattice relaxation time (T1) and spin-spin relaxation time (T2) measurements of C4 solutions with varying cobalt dichloride concentrations to determine the corresponding relaxivities, r1 and r2. These relaxation parameters were investigated at different field strengths, temperatures and orientations. T1 measurements obtained at 1.5 T and 3.0 T, as well as at room and body temperature, showed that r1 is field-independent and temperature-independent. Conversely, the T2 values at 3.0 T were shorter than at 1.5 T, while the T2 values at body temperature were slightly higher than at room temperature. By examining the relaxivities with the C4 vials aligned in three different planes, we found no orientation-dependence. With these relaxation characteristics, we aim to develop pulse sequences that will enhance the C4 signal against prostatic stroma. Ultimately, the use of C4 as a positive contrast agent marker will encourage the use of MRI to obtain an accurate representation of the radiation dose delivered to the prostate and surrounding normal anatomical structures.

Pulse sequence considerations for simulation and postimplant dosimetry of prostate brachytherapy

“…Without the markers, the seeds’ appearance may be difficult to distinguish from other dark signal regions, such as needle tracks, spacers, and vasculature. Presently, the concentration of solution in the C4 markers has been optimized for T1-weighted imaging (26,37,38). It is possible that additional optimization of the MR pulse sequences, concentration of the seed markers, or different types of markers will further improve the signals in the different types of images (such as CISS images), providing even better localization of the seed markers and visualization of the anatomy.…”

“…For this purpose, Frank et al successfully designed markers with cobalt chloride:N-acetylcysteine encapsulated in a polymer capsule (Sirius; C4 Imaging, Houston, TX) (15,16). The C4 markers have a markedly shortened T1 of approximately 100 ms at 1.5 Tesla (26). Therefore, they are best visualized on T1-weighted images.…”

Image‐guided prostate brachytherapy should be MRI‐based

“…Current research is studying a contrast agent that may produce MRI signals of seed positions similar to dummy seeds in conventional brachytherapy. 9,10 However, even if a new contrast becomes available, the scan would require a specific pulse sequence and be encumbered by the inherent geographic uncertainty of MRI.…”

Permanent prostate brachytherapy postimplant magnetic resonance imaging dosimetry using positive contrast magnetic resonance imaging markers

“…The markers are positioned between prostate brachytherapy seeds within a brachytherapy strand at the positions of traditional strand spacers allowing for potential seed identification on MRI. Preclinical studies have confirmed the ability of the markers to produce positive contrast in phantoms, and have identified appropriate MRI sequences for identification of the markers (17). These markers demonstrate minimal potential biotoxicity (18), are FDA approved, and have been implemented into our prostate brachytherapy program at our institution.…”