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Quantitative Imaging Biomarkers for 90Y Distribution on Bremsstrahlung SPECT After Resin-Based Radioembolization.

ABSTRACT: Our purpose was to identify baseline imaging features in patients with liver cancer that correlate with 90Y distribution on postprocedural SPECT and predict tumor response to transarterial radioembolization (TARE). Methods: This retrospective study was approved by the institutional review board and included 38 patients with hepatocellular carcinoma (HCC) (n = 23; 18/23 men; mean age, 62.39 ± 8.62 y; 34 dominant tumors) and non-HCC hepatic malignancies (n = 15; 9/15 men; mean age, 61.13 ± 11.51 y; 24 dominant tumors) who underwent 40 resin-based TARE treatments (August 2012 to January 2018). Multiphasic contrast-enhanced MRI or CT was obtained before and Bremsstrahlung SPECT within 2 h after TARE. Total tumor volume (cm3) and enhancing tumor volume (ETV [cm3] and % of total tumor volume), and total and enhancing tumor burden (%), were volumetrically assessed on baseline imaging. Up to 2 dominant tumors per treated lobe were analyzed. After multimodal image registration of baseline imaging and SPECT/CT, 90Y distribution was quantified on SPECT as tumor-to-normal-liver ratio (TNR). Response was assessed according to RECIST1.1 and quantitative European Association for the Study of the Liver criteria. Clinical parameters were also assessed. Statistical tests included Mann-Whitney U, Pearson correlation, and linear regression. Results: In HCC patients, high baseline ETV% significantly correlated with high TNR on SPECT, demonstrating greater 90Y uptake in the tumor relative to the liver parenchyma (P < 0.001). In non-HCC patients, a correlation between ETV% and TNR was observed as well (P = 0.039). Follow-up imaging for response assessments within 1-4 mo after TARE was available for 23 patients with 25 treatments. The change of ETV% significantly correlated with TNR in HCC (P = 0.039) but not in non-HCC patients (P = 0.886). Additionally, Child-Pugh class B patients demonstrated significantly more 90Y deposition in nontumorous liver than Child-Pugh A patients (P = 0.021). Conclusion: This study identified ETV% as a quantifiable imaging biomarker on preprocedural MRI and CT to predict 90Y distribution on postprocedural SPECT in HCC and non-HCC. However, the relationship between the preferential uptake of 90Y to the tumor and tumor response after radioembolization could be validated only for HCC.

SUBMITTER: Schobert I

PROVIDER: S-EPMC6681698 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Project description:BackgroundAfter yttrium-90 ((90)Y) microsphere radioembolization (RE), evaluation of extrahepatic activity and liver dosimetry is typically performed on (90)Y Bremsstrahlung SPECT images. Since these images demonstrate a low quantitative accuracy, (90)Y PET has been suggested as an alternative. The aim of this study is to quantitatively compare SPECT and state-of-the-art PET on the ability to detect small accumulations of (90)Y and on the accuracy of liver dosimetry.Methodology/principal findingsSPECT/CT and PET/CT phantom data were acquired using several acquisition and reconstruction protocols, including resolution recovery and Time-Of-Flight (TOF) PET. Image contrast and noise were compared using a torso-shaped phantom containing six hot spheres of various sizes. The ability to detect extra- and intrahepatic accumulations of activity was tested by quantitative evaluation of the visibility and unique detectability of the phantom hot spheres. Image-based dose estimates of the phantom were compared to the true dose. For clinical illustration, the SPECT and PET-based estimated liver dose distributions of five RE patients were compared. At equal noise level, PET showed higher contrast recovery coefficients than SPECT. The highest contrast recovery coefficients were obtained with TOF PET reconstruction including resolution recovery. All six spheres were consistently visible on SPECT and PET images, but PET was able to uniquely detect smaller spheres than SPECT. TOF PET-based estimates of the dose in the phantom spheres were more accurate than SPECT-based dose estimates, with underestimations ranging from 45% (10-mm sphere) to 11% (37-mm sphere) for PET, and 75% to 58% for SPECT, respectively. The differences between TOF PET and SPECT dose-estimates were supported by the patient data.Conclusions/significanceIn this study we quantitatively demonstrated that the image quality of state-of-the-art PET is superior over Bremsstrahlung SPECT for the assessment of the (90)Y microsphere distribution after radioembolization.

Project description:Post-therapy quantitative 90Y bremsstrahlung single photon emission computed tomography (SPECT) has shown great potential to provide reliable activity estimates, which are essential for dose verification. Typically 90Y imaging is performed with high- or medium-energy collimators. However, the energy spectrum of 90Y bremsstrahlung photons is substantially different than typical for these collimators. In addition, dosimetry requires quantitative images, and collimators are not typically optimized for such tasks. Optimizing a collimator for 90Y imaging is both novel and potentially important. Conventional optimization methods are not appropriate for 90Y bremsstrahlung photons, which have a continuous and broad energy distribution. In this work, the authors developed a parallel-hole collimator optimization method for quantitative tasks that is particularly applicable to radionuclides with complex emission energy spectra. The authors applied the proposed method to develop an optimal collimator for quantitative 90Y bremsstrahlung SPECT in the context of microsphere radioembolization.To account for the effects of the collimator on both the bias and the variance of the activity estimates, the authors used the root mean squared error (RMSE) of the volume of interest activity estimates as the figure of merit (FOM). In the FOM, the bias due to the null space of the image formation process was taken in account. The RMSE was weighted by the inverse mass to reflect the application to dosimetry; for a different application, more relevant weighting could easily be adopted. The authors proposed a parameterization for the collimator that facilitates the incorporation of the important factors (geometric sensitivity, geometric resolution, and septal penetration fraction) determining collimator performance, while keeping the number of free parameters describing the collimator small (i.e., two parameters). To make the optimization results for quantitative 90Y bremsstrahlung SPECT more general, the authors simulated multiple tumors of various sizes in the liver. The authors realistically simulated human anatomy using a digital phantom and the image formation process using a previously validated and computationally efficient method for modeling the image-degrading effects including object scatter, attenuation, and the full collimator-detector response (CDR). The scatter kernels and CDR function tables used in the modeling method were generated using a previously validated Monte Carlo simulation code.The hole length, hole diameter, and septal thickness of the obtained optimal collimator were 84, 3.5, and 1.4 mm, respectively. Compared to a commercial high-energy general-purpose collimator, the optimal collimator improved the resolution and FOM by 27% and 18%, respectively.The proposed collimator optimization method may be useful for improving quantitative SPECT imaging for radionuclides with complex energy spectra. The obtained optimal collimator provided a substantial improvement in quantitative performance for the microsphere radioembolization task considered.

Project description:PURPOSE:In 90 Y microsphere radioembolization (RE), accurate post-therapy imaging-based dosimetry is important for establishing absorbed dose versus outcome relationships for developing future treatment planning strategies. Additionally, accurately assessing microsphere distributions is important because of concerns for unexpected activity deposition outside the liver. Quantitative 90 Y imaging by either SPECT or PET is challenging. In 90 Y SPECT model based methods are necessary for scatter correction because energy window-based methods are not feasible with the continuous bremsstrahlung energy spectrum. The objective of this work was to implement and evaluate a scatter estimation method for accurate 90 Y bremsstrahlung SPECT/CT imaging. METHODS:Since a fully Monte Carlo (MC) approach to 90 Y SPECT reconstruction is computationally very demanding, in the present study the scatter estimate generated by a MC simulator was combined with an analytical projector in the 3D OS-EM reconstruction model. A single window (105 to 195-keV) was used for both the acquisition and the projector modeling. A liver/lung torso phantom with intrahepatic lesions and low-uptake extrahepatic objects was imaged to evaluate SPECT/CT reconstruction without and with scatter correction. Clinical application was demonstrated by applying the reconstruction approach to five patients treated with RE to determine lesion and normal liver activity concentrations using a (liver) relative calibration. RESULTS:There was convergence of the scatter estimate after just two updates, greatly reducing computational requirements. In the phantom study, compared with reconstruction without scatter correction, with MC scatter modeling there was substantial improvement in activity recovery in intrahepatic lesions (from > 55% to > 86%), normal liver (from 113% to 104%), and lungs (from 227% to 104%) with only a small degradation in noise (13% vs. 17%). Similarly, with scatter modeling contrast improved substantially both visually and in terms of a detectability index, which was especially relevant for the low uptake extrahepatic objects. The trends observed for the phantom were also seen in the patient studies where lesion activity concentrations and lesion-to-liver concentration ratios were lower for SPECT without scatter correction compared with reconstruction with just two MC scatter updates: in eleven lesions the mean uptake was 4.9 vs. 7.1 MBq/mL (P = 0.0547), the mean normal liver uptake was 1.6 vs. 1.5 MBq/mL (P = 0.056) and the mean lesion-to-liver uptake ratio was 2.7 vs. 4.3 (P = 0.0402) for reconstruction without and with scatter correction respectively. CONCLUSIONS:Quantitative accuracy of 90 Y bremsstrahlung imaging can be substantially improved with MC scatter modeling without significant degradation in image noise or intensive computational requirements.

Project description:Yttrium-90 ((90)Y) is one of the most commonly used radionuclides in targeted radionuclide therapy (TRT). Since it decays with essentially no gamma photon emissions, surrogate radionuclides (e.g., (111)In) or imaging agents (e.g., (99m)Tc MAA) are typically used for treatment planning. It would, however, be useful to image (90)Y directly in order to confirm that the distributions measured with these other radionuclides or agents are the same as for the (90)Y labeled agents. As a result, there has been a great deal of interest in quantitative imaging of (90)Y bremsstrahlung photons using single photon emission computed tomography (SPECT) imaging. The continuous and broad energy distribution of bremsstrahlung photons, however, imposes substantial challenges on accurate quantification of the activity distribution. The aim of this work was to develop and evaluate an improved quantitative (90)Y bremsstrahlung SPECT reconstruction method appropriate for these imaging applications.Accurate modeling of image degrading factors such as object attenuation and scatter and the collimator-detector response is essential to obtain quantitatively accurate images. All of the image degrading factors are energy dependent. Thus, the authors separated the modeling of the bremsstrahlung photons into multiple categories and energy ranges. To improve the accuracy, the authors used a bremsstrahlung energy spectrum previously estimated from experimental measurements and incorporated a model of the distance between (90)Y decay location and bremsstrahlung emission location into the SIMIND code used to generate the response functions and kernels used in the model. This improved Monte Carlo bremsstrahlung simulation was validated by comparison to experimentally measured projection data of a (90)Y line source. The authors validated the accuracy of the forward projection model for photons in the various categories and energy ranges using the validated Monte Carlo (MC) simulation method. The forward projection model was incorporated into an iterative ordered subsets-expectation maximization (OS-EM) reconstruction code to allow for quantitative SPECT reconstruction. The resulting code was validated using both a physical phantom experiment with spherical objects in a warm background and a realistic anatomical phantom simulation. In the physical phantom study, the authors evaluated the method in terms of quantitative accuracy of activity estimates in the spheres; in the simulation study, the authors evaluated the accuracy and precision of activity estimates from various organs and compared them to results from a previously proposed method.The authors demonstrated excellent agreement between the experimental measurement and Monte Carlo simulation. In the XCAT phantom simulation, the proposed method achieved much better accuracy in the modeling (error in photon counts was -1.1 %) compared to a previously proposed method (errors were more than 20 %); the quantitative accuracy of activity estimates was excellent for all organs (errors were from -1.6 % to 11.9 %) and comparable to previously published results for (131)I using the same collimator.The proposed (90)Y bremsstrahlung SPECT reconstruction method provided very accurate estimates of organ activities, with accuracies approaching those previously observed for (131)I. The method may be useful in verifying organ doses for targeted radionuclide therapy using (90)Y.

Project description:BackgroundThe introduction of hybrid SPECT/CT devices enables quantitative imaging in SPECT, providing a methodological setup for quantitation using SPECT tracers comparable to PET/CT. We evaluated a specific quantitative reconstruction algorithm for SPECT data using a 99mTc-filled NEMA phantom. Quantitative and qualitative image parameters were evaluated for different parametrizations of the acquisition and reconstruction protocol to identify an optimized quantitative protocol.ResultsThe reconstructed activity concentration (ACrec) and the signal-to-noise ratio (SNR) of all examined protocols (n = 16) were significantly affected by the parametrization of the weighting factor k used in scatter correction, the total number of iterations and the sphere volume (all, p < 0.0001). The two examined SPECT acquisition protocols (with 60 or 120 projections) had a minor impact on the ACrec and no significant impact on the SNR. In comparison to the known AC, the use of default scatter correction (k = 0.47) or object-specific scatter correction (k = 0.18) resulted in an underestimation of ACrec in the largest sphere volume (26.5 ml) by - 13.9 kBq/ml (- 16.3%) and - 7.1 kBq/ml (- 8.4%), respectively. An increase in total iterations leads to an increase in estimated AC and a decrease in SNR. The mean difference between ACrec and known AC decreased with an increasing number of total iterations (e.g., for 20 iterations (2 iterations/10 subsets) = - 14.6 kBq/ml (- 17.1%), 240 iterations (24i/10s) = - 8.0 kBq/ml (- 9.4%), p < 0.0001). In parallel, the mean SNR decreased significantly from 2i/10s to 24i/10s by 76% (p < 0.0001).ConclusionQuantitative SPECT imaging is feasible with the used reconstruction algorithm and hybrid SPECT/CT, and its consistent implementation in diagnostics may provide perspectives for quantification in routine clinical practice (e.g., assessment of bone metabolism). When combining quantitative analysis and diagnostic imaging, we recommend using two different reconstruction protocols with task-specific optimized setups (quantitative vs. qualitative reconstruction). Furthermore, individual scatter correction significantly improves both quantitative and qualitative results.

Project description:BackgroundTransarterial radioembolization (TARE) with 90Y-labeled glass and resin microspheres is one of the primary treatment strategies for advanced-stage primary and metastatic hepatocellular carcinoma (HCC). However, difficulties of real-time monitoring post administration and embolic hypoxia influence treatment prognosis. In this study, we developed a new biodegradable polymer microsphere that can simultaneously load 177Lu and MgO nanoparticle, and evaluated the TARE therapeutic efficacy and biosafety of 177Lu-PDA-CS-MgO microspheres for HCC treatment.MethodsChitosan microspheres were synthesized through emulsification crosslink reaction and then conducted surface modification with polydopamine (PDA). The 177Lu and nano MgO were conjugated to microspheres using active chemical groups of PDA. The characteristics of radionuclide loading efficiency, biodegradability, blood compatibility, and anti-tumor effectwere evaluated both in vitro and in vivo. SPECT/CT imaging was performed to monitor bio-distribution and bio-stability of 177Lu-PDA-CS-MgO after TARE treatment. The survival duration of each rat was monitored. HE analysis, TUNEL analysis, immunohistochemical analysis, and western blot analysis were conducted to explore the anti-tumor effect and mechanism of composited microspheres. Body weight, liver function, blood routine examination were monitored at different time points to evaluate the bio-safety of microspheres.ResultsThe composite 177Lu-PDA-CS-MgO microsphere indicated satisfactory degradability, biocompatibility, radionuclide loading efficiency and radiochemical stability in vitro. Cellular evaluation showed that 177Lu-PDA-CS-MgO had significant anti-tumor effect and blocked tumor cell cycles in S phase. Surgical TARE treatment with 177Lu-PDA-CS-MgO significantly prolonged the medial survival time from 49 d to 105 d, and effectively inhibited primary tumor growth and small metastases spreading. Moreover, these microspheres indicated ideal in vivo stability and allowed real-time SPECT/CT monitoring for up to 8 weeks. Immunostaining and immunoblotting results also confirmed that 177Lu-PDA-CS-MgO had potential in suppressing tumor invasion and angiogenesis, and improved embolic hypoxia in HCC tissues. Further evaluations of body weight, blood test, and pathological analysis indicated good biosafety of 177Lu-PDA-CS-MgO microspheres in vivo.ConclusionOur study demonstrated that 177Lu-PDA-CS-MgO microsphere hold great potential as interventional brachytherapy candidate for HCC therapy. Polymer composite microspheres loading 177Lu radionuclide and MgO nanoparticles for interventional radioembolization therapy and real-time SPECT imaging of hepatic cancer.

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Quantitative Imaging Biomarkers for 90Y Distribution on Bremsstrahlung SPECT After Resin-Based Radioembolization.

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