Dose-point Kernel Convolution Research Articles

Prediction of tumor response and patient outcome after radioembolization of hepatocellular carcinoma using 90Y-PET-computed tomography dosimetry.

90Y-radioembolization using glass or resin microspheres is increasingly used for the treatment of hepatocellular carcinoma (HCC). The aim of this retrospective study is to determine the prognostic relevance of dosimetric parameters defined with 90Y-PET-CT obtained immediately after radioembolization. Forty-five HCC patients, mostly with multiple lesions, were treated by radioembolization between 2011 and 2017. After treatment, all underwent a 90Y PET-CT with time of flight reconstruction (90Y-TOF-PET-CT). Tumor absorbed dose and cumulative tumor dose-volume histogram were calculated using a dose point Kernel convolution algorithm. The radiological tumor response was assessed using modified (m)-RECIST criteria. Progression-free-survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and Cox regression analysis. Twenty-six patients were treated with glass microspheres (73 lesions) and nineteen with resin microspheres (60 lesions). Thresholds of 118 and 61 Gy for glass and resin microspheres respectively correlate well with radiological response with a positive predictive value (PPV) of 98 and 80% and discriminate patient outcome with regard to PFS (P = 0.03 and 0.005) and OS (P = 0.003 and 0.007). Using dose volume histogram, a minimal absorbed dose of 40 Gy in 66% of the tumor volume (defined as D66) was highly predictive of radiological response (PPV = 94%), PFS (P < 0.001) and OS (P = 0. 008), for either device. Dosimetric parameters obtained using 90Y-PET-CT are predictive of tumor response, PFS and OS. In clinical practice, a systematic dosimetric evaluation using 90Y PET should be implemented to help predicting patient outcomes.

Impact of the dosimetry approach on the resulting 90Y radioembolization planned absorbed doses based on 99mTc-MAA SPECT-CT: is there agreement between dosimetry methods?

BackgroundPrior radioembolization, a simulation using 99mTc-macroaggregated albumin as 90Y-microspheres surrogate is performed. Gamma scintigraphy images (planar, SPECT, or SPECT-CT) are acquired to evaluate intrahepatic 90Y-microspheres distribution and detect possible extrahepatic and lung shunting. These images may be used for pre-treatment dosimetry evaluation to calculate the 90Y activity that would get an optimal tumor response while sparing healthy tissues.Several dosimetry methods are available, but there is still no consensus on the best methodology to calculate absorbed doses. The goal of this study was to retrospectively evaluate the impact of using different dosimetry approaches on the resulting 90Y-radioembolization pre-treatment absorbed dose evaluation based on 99mTc-MAA images.MethodsAbsorbed doses within volumes of interest resulting from partition model (PM) and 3D voxel dosimetry methods (3D-VDM) (dose-point kernel convolution and local deposition method) were evaluated. Additionally, a new “Multi-tumor Partition Model” (MTPM) was developed. The differences among dosimetry approaches were evaluated in terms of mean absorbed dose and dose volume histograms within the volumes of interest.ResultsDifferences in mean absorbed dose among dosimetry methods are higher in tumor volumes than in non-tumoral ones. The differences between MTPM and both 3D-VDM were substantially lower than those observed between PM and any 3D-VDM. A poor correlation and concordance were found between PM and the other studied dosimetry approaches.DVH obtained from either 3D-VDM are pretty similar in both healthy liver and individual tumors. Although no relevant global differences, in terms of absorbed dose in Gy, between both 3D-VDM were found, important voxel-by-voxel differences have been observed.ConclusionsSignificant differences among the studied dosimetry approaches for 90Y-radioembolization treatments exist. Differences do not yield a substantial impact in treatment planning for healthy tissue but they do for tumoral liver.An individual segmentation and evaluation of the tumors is essential. In patients with multiple tumors, the application of PM is not optimal and the 3D-VDM or the new MTPM are suggested instead. If a 3D-VDM method is not available, MTPM is the best option. Furthermore, both 3D-VDM approaches may be indistinctly used.

DOSIS: An integrated computational tool for patient-specific dosimetry in nuclear medicine by Monte Carlo and dose point kernel approaches

The use of radiolabeled molecules for tumor targeting constitutes a remarkable technique for the treatment of systemic malignancies. An accurate patient-specific dosimetry in nuclear medicine procedures should be a relevant pre-requisite in order to achieve the required lethal damage to tumor cells while maintaining possible side-effects to normal tissues at tolerable levels. It is desired to assess in vivo the radiopharmaceutical distribution for further estimation of absorbed dose released to target and involved organs. In this context, it was developed a computational toolkit, called DOSIS, in order to perform patient-specific dosimetry based on personalized patient anatomy and biodistribution of radionuclides both obtained by currently available dual PET/CT or SPECT/CT facilities. This work is focused on comparing 3D dose distributions obtained by DOSIS performing full stochastic Monte Carlo simulations versus analogue distributions obtained with analytical approaches like dose point kernel convolution and local energy deposition, when considering non-homogeneous activity or density distributions at different scales. Mathematical virtual phantoms were created for this study in order to compare results with other calculation methods. Some of the beta-emitters radionuclides commonly used for therapy (90Y, 131I, 177Lu) were investigated, and emissions of beta-particles, conversion electrons, gamma radiation, and characteristic X-rays were considered. DOSIS implements a novel code devoted to managing radiation transport simulation by means of PENELOPE Monte Carlo general-purpose routines on voxelized geometries defined by 3D mass and activity distributions. Both distributions can be defined through patients-specific images, or pre-defined virtual phantoms. Results preliminary confirmed DOSIS as a reliable and accurate toolkit for personalized internal dosimetry along with highlighting advantages/drawbacks of the different calculation schemes proposed.

SU‐E‐CAMPUS‐I‐06: Y90 PET/CT for the Instantaneous Determination of Both Target and Non‐Target Absorbed Doses Following Hepatic Radioembolization

PurposeThe process of converting Yttrium‐90 (Y90) PET/CT images into 3D absorbed dose maps will be explained. The simple methods presented will allow the medical physicst to analyze Y90 PET images following radioembolization and determine the absorbed dose to tumor, normal liver parenchyma and other areas of interest, without application of Monte‐Carlo radiation transport or dose‐point‐kernel (DPK) convolution.MethodsAbsorbed dose can be computed from Y90 PET/CT images based on the premise that radioembolization is a permanent implant with a constant relative activity distribution after infusion. Many Y90 PET/CT publications have used DPK convolution to obtain 3D absorbed dose maps. However, this method requires specialized software limiting clinical utility. The Local Deposition method, an alternative to DPK convolution, can be used to obtain absorbed dose and requires no additional computer processing. Pixel values from regions of interest drawn on Y90 PET/CT images can be converted to absorbed dose (Gy) by multiplication with a scalar constant.ResultsThere is evidence that suggests the Local Deposition method may actually be more accurate than DPK convolution and it has been successfully used in a recent Y90 PET/CT publication. We have analytically compared dose‐volume‐histograms (DVH) for phantom hot‐spheres to determine the difference between the DPK and Local Deposition methods, as a function of PET scanner point‐spread‐function for Y90. We have found that for PET/CT systems with a FWHM greater than 3.0 mm when imaging Y90, the Local Deposition Method provides a more accurate representation of DVH, regardless of target size than DPK convolution.ConclusionUsing the Local Deposition Method, post‐radioembolization Y90 PET/CT images can be transformed into 3D absorbed dose maps of the liver. An interventional radiologist or a Medical Physicist can perform this transformation in a clinical setting, allowing for rapid prediction of treatment efficacy by comparison to published tumoricidal thresholds.

A Comparison of Techniques for (90)Y PET/CT Image-Based Dosimetry Following Radioembolization with Resin Microspheres.

90Y PET/CT following radioembolization has recently been established as a viable diagnostic tool, capable of producing images that are both quantitative and have superior image quality than alternative 90Y imaging modalities. Because radioembolization is assumed to be a permanent implant, it is possible to convert quantitative 90Y PET image sets into data representative of spatial committed absorbed-dose. Multiple authors have performed this transformation using dose-point kernel (DPK) convolution to account for the transport of the high-energy 90Y β-particles. This article explores a technique called the Local Deposition Method (LDM), an alternative to DPK convolution for 90Y image-based dosimetry. The LDM assumes that the kinetic energy from each 90Y β-particle is deposited locally, within the voxel where the decay occurred. Using the combined analysis of phantoms scanned using 90Y PET/CT and ideal mathematical phantoms, an accuracy comparison of DPK convolution and the LDM has been performed. Based on the presented analysis, DPK convolution provides no detectible accuracy benefit over the LDM for 90Y PET-based dosimetry. For PET systems with 90Y resolution poorer than 3.25 mm at full-width and half-max using a small voxel size, the LDM may produce a dosimetric solution that is more accurate than DPK convolution under ideal conditions; however, image noise can obscure some of the perceived benefit. As voxel size increases and resolution decreases, differences between the LDM and DPK convolution are reduced. The LDM method of post-radioembolization dosimetry has the advantage of not requiring additional post-processing. The provided conversion factors can be used to determine committed absorbed-dose using conventional PET image analysis tools. The LDM is a recommended option for routine post-radioembolization 90Y dosimetry based on PET/CT imaging.

Improved tumour response prediction with equivalent uniform dose in pre-clinical study using direct intratumoural infusion of liposome-encapsulated 186Re radionuclides

Crucial to all cancer therapy modalities is a strong correlation between treatment and effect. Predictability of therapy success/failure allows for the optimization of treatment protocol and aids in the decision of whether additional treatment is necessary to prevent tumour progression. This work evaluated the relationship between cancer treatment and effect for intratumoural infusions of liposome-encapsulated 186Re to head and neck squamous cell carcinoma xenografts of nude rats. Absorbed dose calculations using a dose-point kernel convolution technique showed significant intratumoural dose heterogeneity due to the short range of the beta-particle emissions. The use of three separate tumour infusion locations improved dose homogeneity compared to a single infusion location as a result of a more uniform radioactivity distribution. An improved dose–response correlation was obtained when using effective uniform dose (EUD) calculations based on a generic set of radiobiological parameters (R2 = 0.84) than when using average tumour absorbed dose (R2 = 0.22). Varying radiobiological parameter values over ranges commonly used for all types of tumours showed little effect on EUD calculations, which suggests that individualized parameter use is of little significance as long as the intratumoural dose heterogeneity is taken into consideration in the dose–response relationship. The improved predictability achieved when using EUD calculations for this cancer therapy modality may be useful for treatment planning and evaluation.

Radiobiological characterization of post-lumpectomy focal brachytherapy with lipid nanoparticle-carried radionuclides

Post-operative radiotherapy has commonly been used for early stage breast cancer to treat residual disease. The primary objective of this work was to characterize, through dosimetric and radiobiological modeling, a novel focal brachytherapy technique which uses direct intracavitary infusion of β-emitting radionuclides (186Re/188Re) carried by lipid nanoparticles (liposomes). Absorbed dose calculations were performed for a spherical lumpectomy cavity with a uniformly injected activity distribution using a dose point kernel convolution technique. Radiobiological indices were used to relate predicted therapy outcome and normal tissue complication of this technique with equivalent external beam radiotherapy treatment regimens. Modeled stromal damage was used as a measure of the inhibition of the stimulatory effect on tumor growth driven by the wound healing response. A sample treatment plan delivering 50 Gy at a therapeutic range of 2.0 mm for 186Re-liposomes and 5.0 mm for 188Re-liposomes takes advantage of the dose delivery characteristics of the β-emissions, providing significant EUD (58.2 Gy and 72.5 Gy for 186Re and 188Re, respectively) with a minimal NTCP (0.046%) of the healthy ipsilateral breast. Modeling of kidney BED and ipsilateral breast NTCP showed that large injected activity concentrations of both radionuclides could be safely administered without significant complications.

Postlumpectomy Focal Brachytherapy for Simultaneous Treatment of Surgical Cavity and Draining Lymph Nodes

The primary objective was to investigate a novel focal brachytherapy technique using lipid nanoparticle (liposome)-carried β-emitting radionuclides (rhenium-186 [(186)Re]/rhenium-188 [(188)Re]) to simultaneously treat the postlumpectomy surgical cavity and draining lymph nodes. Cumulative activity distributions in the lumpectomy cavity and lymph nodes were extrapolated from small animal imaging and human lymphoscintigraphy data. Absorbed dose calculations were performed for lumpectomy cavities with spherical and ellipsoidal shapes and lymph nodes within human subjects by use of the dose point kernel convolution method. Dose calculations showed that therapeutic dose levels within the lumpectomy cavity wall can cover 2- and 5-mm depths for (186)Re and (188)Re liposomes, respectively. The absorbed doses at 1 cm sharply decreased to only 1.3% to 3.7% of the doses at 2 mm for (186)Re liposomes and 5 mm for (188)Re liposomes. Concurrently, the draining sentinel lymph nodes would receive a high focal therapeutic absorbed dose, whereas the average dose to 1 cm of surrounding tissue received less than 1% of that within the nodes. Focal brachytherapy by use of (186)Re/(188)Re liposomes was theoretically shown to be capable of simultaneously treating the lumpectomy cavity wall and draining sentinel lymph nodes with high absorbed doses while significantly lowering dose to surrounding healthy tissue. In turn, this allows for dose escalation to regions of higher probability of containing residual tumor cells after lumpectomy while reducing normal tissue complications.

Validation of a dose-point kernel convolution technique for internal dosimetry

The objective of this study was to validate a dose-point kernel convolution technique that provides a three-dimensional (3D) distribution of absorbed dose from a 3D distribution of the radionuclide 131I. A dose-point kernel for the penetrating radiations was calculated by a Monte Carlo simulation and cast in a 3D rectangular matrix. This matrix was convolved with the 3D activity map furnished by quantitative single-photon-emission computed tomography (SPECT) to provide a 3D distribution of absorbed dose. The convolution calculation was performed using a 3D fast Fourier transform (FFT) technique, which takes less than 40 s for a 128*128*16 matrix on an Intel 486 DX2 (66 MHz) personal computer. The calculated photon absorbed dose was compared with values measured by thermoluminescent dosimeters (TLDS) inserted along the diameter of a 22 cm diameter annular source of 131I. The mean and standard deviation of the percentage difference between the measurements and the calculations were equal to -1% and 3.6%, respectively. This convolution method was also used to calculate the 3D dose distribution in an Alderson abdominal phantom containing a liver, a spleen, and a spherical tumour volume loaded with various concentrations of 131I. By averaging the dose calculated throughout the liver, spleen, and tumour the dose-point kernel approach was compared with values derived using the MIRD formalism, and found to agree to better than 15%.