MR-based source localization for MR-guided HDR brachytherapy.

For the purpose of MR-guided high-dose-rate (HDR) brachytherapy, a method for real-time localization of an HDR brachytherapy source was developed, which requires high spatial and temporal resolutions. MR-based localization of an HDR source serves two main aims. First, it enables real-time treatment verification by determination of the HDR source positions during treatment. Second, when using a dummy source, MR-based source localization provides an automatic detection of the source dwell positions after catheter insertion, allowing elimination of the catheter reconstruction procedure. Localization of the HDR source was conducted by simulation of the MR artifacts, followed by a phase correlation localization algorithm applied to the MR images and the simulated images, to determine the position of the HDR source in the MR images. To increase the temporal resolution of the MR acquisition, the spatial resolution was decreased, and a subpixel localization operation was introduced. Furthermore, parallel imaging (sensitivity encoding) was applied to further decrease the MR scan time. The localization method was validated by a comparison with CT, and the accuracy and precision were investigated. The results demonstrated that the described method could be used to determine the HDR source position with a high accuracy (0.4-0.6 mm) and a high precision (⩽0.1 mm), at high temporal resolutions (0.15-1.2 s per slice). This would enable real-time treatment verification as well as an automatic detection of the source dwell positions.

Monte Carlo study of the impact of a magnetic field on the dose distribution in MRI-guided HDR brachytherapy using Ir-192.

In the process of developing a robotic MRI-guided high-dose-rate (HDR) prostate brachytherapy treatment, the influence of the MRI scanner's magnetic field on the dose distribution needs to be investigated. A magnetic field causes a deflection of electrons in the plane perpendicular to the magnetic field, and it leads to less lateral scattering along the direction parallel with the magnetic field. Monte Carlo simulations were carried out to determine the influence of the magnetic field on the electron behavior and on the total dose distribution around an Ir-192 source. Furthermore, the influence of air pockets being present near the source was studied. The Monte Carlo package Geant4 was utilized for the simulations. The simulated geometries consisted of a simplified point source inside a water phantom. Magnetic field strengths of 0 T, 1.5 T, 3 T, and 7 T were considered. The simulation results demonstrated that the dose distribution was nearly unaffected by the magnetic field for all investigated magnetic field strengths. Evidence was found that, from a dose perspective, the HDR prostate brachytherapy treatment using Ir-192 can be performed safely inside the MRI scanner. No need was found to account for the magnetic field during treatment planning. Nevertheless, the presence of air pockets in close vicinity to the source, particularly along the direction parallel with the magnetic field, appeared to be an important point for consideration.

Simultaneous R2*, R2, and R2' quantification by combining S0 estimation of the free induction decay with a single spin echo: A single acquisition method for R2 insensitive quantification of holmium-166-loaded microspheres.

PURPOSE: To present a new method, S0 estimation of the free induction decay combined with a single spin echo measurement (SOFIDSE), that enables simultaneous measurements of R2*, R2, and R2' in order to quantify the local concentration of holmium microspheres (Ho-MS) for radioembolization. THEORY AND METHODS: SOFIDSE estimates R2* and the signal magnitude at time point 0, S0, from a multigradient echo readout of the free induction decay and subsequently estimates R2 using S0 and a single spin echo, from which R2' is deducted. The method was evaluated by comparing SOFIDSE R2 values with values obtained from shifted spin echo (SSE) measurements on a phantom setup containing Ho-MS and from dual spin echo measurements on a healthy volunteer. RESULTS: On average, SOFIDSE showed a small overestimation of R2 values compared with SSE independent of the microsphere concentration. R2' values determined by subtraction of either SOFIDSE R2 or SSE R2 from R2* showed excellent agreement (correlation coefficient = 1; P = 9 · 10(-11)). The Ho-MS-induced R2' values obtained by SOFIDSE were insensitive to the R2 value of the tissue in which they resided. CONCLUSION: SOFIDSE enables quantification of Ho-MS, in media with spatially or temporally varying R2 values, in a single acquisition.

Center-out radial sampling with off-resonant reconstruction for efficient and accurate localization of punctate and elongated paramagnetic structures.

Accurate localization of interventional devices, for example, needles and brachytherapy seeds, is desired for interventional procedures. MRI is usually considered unsuitable for this purpose, as the induced signal voids and signal pile-ups do not necessarily represent the exact location of the devices. Center-out radial sampling with off-resonance reception (co-RASOR) has been shown to solve this problem by repositioning the signal pile-up into the geometrical center of the interventional devices. However, the multiple acquisitions required for co-RASOR resulted in a low efficiency and unsuitability for near real-time interventional purposes. Herein, we aim to increase the efficiency of co-RASOR by relying on multiple off-resonance reconstructions of a single acquisition rather than on multiple acquisitions. The soundness of this approach is shown by demonstrating the equivalence of acquisition co-RASOR and reconstruction co-RASOR, both theoretically and experimentally. An algorithm is proposed and evaluated to obtain the geometric centers of the devices, while suppressing the background. This procedure is shown to be effective, in vitro as well as ex vivo, and to yield signal intensity increases in the order of 150-400% of the average signal, in the geometric center of a brachytherapy seed and a needle, respectively. The geometric accuracy of the resultant images is confirmed by computed tomography.

Towards inherently distortion-free MR images for image-guided radiotherapy on an MRI accelerator.

In MR-guided interventions, it is mandatory to establish a solid relationship between the imaging coordinate system and world coordinates. This is particularly important in image-guided radiotherapy (IGRT) on an MRI accelerator, as the interaction of matter with γ-radiation cannot be visualized. In conventional acquisitions, off-resonance effects cause discrepancies between coordinate systems. We propose to mitigate this by using only phase encoding and to reduce the longer acquisitions by under-sampling and regularized reconstruction. To illustrate the performance of this acquisition in the presence of off-resonance phenomena, phantom and in vivo images are acquired using spin-echo (SE) and purely phase-encoded sequences. Data are retrospectively under-sampled and reconstructed iteratively. We observe accurate geometries in purely phase-encoded images for all cases, whereas SE images of the same phantoms display image distortions. Regularized reconstruction yields accurate phantom images under high acceleration factors. In vivo images were reconstructed faithfully while using acceleration factors up to 4. With the proposed technique, inherently undistorted images with one-to-one correspondence to world coordinates can be obtained. It is a valuable tool in geometry quality assurance, treatment planning and online image guidance. Under-sampled acquisition combined with regularized reconstruction can be used to accelerate the acquisition while retaining geometrical accuracy.

Holmium-166 poly(L-lactic acid) microsphere radioembolisation of the liver: technical aspects studied in a large animal model.

OBJECTIVE: To assess the accuracy of a scout dose of holmium-166 poly(L-lactic acid) microspheres ((166)Ho-PLLA-MS) in predicting the distribution of a treatment dose of (166)Ho-PLLA-MS, using single photon emission tomography (SPECT). METHODS: A scout dose (60 mg) was injected into the hepatic artery of five pigs and SPECT acquired. Subsequently, a 'treatment dose' was administered (540 mg) and SPECT, computed tomography (CT) and magnetic resonance imaging (MRI) of the total dose performed. The two SPECT images of each animal were compared. To validate quantitative SPECT an ex vivo liver was instilled with (166)Ho-PLLA-MS and SPECT acquired. The liver was cut into slices and planar images were acquired, which were registered to the SPECT image. RESULTS: Qualitatively, the scout dose and total dose images were similar, except in one animal because of catheter displacement. Quantitative analysis, feasible in two animals, tended to confirm this similarity (r(2) = 0.34); in the other animal the relation was significantly better (r(2) = 0.66). The relation between the SPECT and planar images acquired from the ex vivo liver was strong (r(2) = 0.90). CONCLUSION: In the porcine model a scout dose of (166)Ho-PLLA-MS can accurately predict the biodistribution of a treatment dose. Quantitative (166)Ho SPECT was validated for clinical application.

Microspheres with ultrahigh holmium content for radioablation of malignancies.

PURPOSE: The aim of this study was to develop microspheres with an ultra high holmium content which can be neutron activated for radioablation of malignancies. These microspheres are proposed to be delivered selectively through either intratumoral injections into solid tumors or administered via an intravascularly placed catheter. METHODS: Microspheres were prepared by solvent evaporation, using holmium acetylacetonate (HoAcAc) crystals as the sole ingredient. Microspheres were characterized using light and scanning electron microscopy, coulter counter, titrimetry, infrared and Raman spectroscopy, differential scanning calorimetry, X-ray powder diffraction, magnetic resonance imaging (MRI), and X-ray computed tomography (CT). RESULTS: Microspheres, thus prepared displayed a smooth surface. The holmium content of the HoAcAc microspheres (44% (w/w)) was higher than the holmium content of the starting material, HoAcAc crystals (33% (w/w)). This was attributed to the loss of acetylacetonate from the HoAcAc complex, during rearrangement of acetylacetonate around the holmium ion. The increase of the holmium content allows for the detection of (sub)microgram amounts of microspheres using MRI and CT. CONCLUSIONS: HoAcAc microspheres with an ultra-high holmium content were prepared. These microspheres are suitable for radioablation of tumors by intratumoral injections or treatment of liver tumors through transcatheter administration.

Clinical effects of transcatheter hepatic arterial embolization with holmium-166 poly(L-lactic acid) microspheres in healthy pigs.

PURPOSE: The aim of this study is to evaluate the toxicity of holmium-166 poly(L-lactic acid) microspheres administered into the hepatic artery in pigs. METHODS: Healthy pigs (20-30 kg) were injected into the hepatic artery with holmium-165-loaded microspheres ((165)HoMS; n=5) or with holmium-166-loaded microspheres ((166)HoMS; n=13). The microspheres' biodistribution was assessed by single-photon emission computed tomography and/or MRI. The animals were monitored clinically, biochemically, and ((166)HoMS group only) hematologically over a period of 1 month ((165)HoMS group) or over 1 or 2 months ((166)HoMS group). Finally, a pathological examination was undertaken. RESULTS: After microsphere administration, some animals exhibited a slightly diminished level of consciousness and a dip in appetite, both of which were transient. Four lethal adverse events occurred in the (166)HoMS group due either to incorrect administration or comorbidity: inadvertent delivery of microspheres into the gastric wall (n=2), preexisting gastric ulceration (n=1), and endocarditis (n=1). AST levels were transitorily elevated post-(166)HoMS administration. In the other blood parameters, no abnormalities were observed. Nuclear scans were acquired from all animals from the (166)HoMS group, and MRI scans were performed if available. In pigs from the (166)HoMS group, atrophy of one or more liver lobes was frequently observed. The actual radioactivity distribution was assessed through ex vivo (166m)Ho measurements. CONCLUSION: It can be concluded that the toxicity profile of HoMS is low. In pigs, hepatic arterial embolization with (166)HoMS in amounts corresponding with liver-absorbed doses of over 100 Gy, if correctly administered, is not associated with clinically relevant side effects. This result offers a good perspective for upcoming patient trials.