Response Assessment and Prediction of Progression-Free Survival by 68Ga-PSMA-11 PET/CT Based on Tumor-to-Liver Ratio (TLR) in Patients with mCRPC Undergoing 177Lu-PSMA-617 Radioligand Therapy.

At present, little is known about the molecular imaging-based response assessment of prostate-specific membrane antigen (PSMA)-targeted radioligand therapy with 177Lutetium (177Lu-PSMA-617 RLT) in metastatic castration-resistant prostate cancer (mCRPC). Our study evaluated the response to RLT using both molecular imaging and biochemical response assessments, and their potential prediction of progression-free survival (PFS). Fifty-one consecutive patients given two cycles of RLT at 6-week intervals were analyzed retrospectively. 68Ga-PSMA-11 PET/CT was obtained about 2 weeks prior to the first and 4-6 weeks after the second cycle. Molecular imaging-based response using SUVpeak and tumor-to-liver ratio (TLR) was determined by modified PERCIST criteria. ∆TLR and ∆SUV were significantly correlated with ∆PSA (p < 0.001, each). After a median follow-up of 49 months, the median PFS (95% CI) was 8.0 (5.9-10.1) months. In univariate analysis, responders showing partial remission (PRPSA and PRTLR) had significantly (p < 0.001, each) longer PFS (median: 10.5 and 9.3 months) than non-responders showing either stable or progressive disease (median: 4.0 and 3.5 months). Response assessment using SUVpeak failed to predict survival. In multivariable analysis, response assessment using TLR was independently associated with PFS (p < 0.001), as was good performance status (p = 0.002). Molecular imaging-based response assessment with 68Ga-PSMA-11 PET/CT using normalization of the total lesion PSMA over healthy liver tissue uptake (TLR) could be an appropriate biomarker to monitor RLT in mCRPC patients and to predict progression-free survival (PFS) of this treatment modality.

Implementation of dose point kernel (DPK) for dose optimization of 177Lu/90Y cocktail radionuclides in internal dosimetry.

BACKGROUND: Due to the importance of choosing the applicable dosimetry method in radionuclide therapy, the present study was conducted to investigate the efficiency of the implementation of Dose Point Kernel (DPK) for dose optimization of 177Lu/90Y Cocktail Radionuclides in internal Dosimetry. METHODS: In this study, simulations and calculations of DPK were performed using the GATE/GEANT4 Monte Carlo code. For specific liver dosimetry, the NCAT phantom and convolution algorithm-based Fast Fourier Transform method was used by MATLAB software. RESULTS: The self-dose of 177Lu and 90Y radionuclides in the liver of NCAT phantom were 1.1708E-13, and 4.8420E-11 (Gy/Bq), respectively, and the cross-dose of 177Lu and 90Y radionuclides out of the liver of NCAT phantom were 2.03615E-16, and 0.8422E-13 (Gy/Bq) respectively. Overall results showed that with an increase the value of 90Y with quarter steps in a cocktail, the amount of the self-dose increase 1.5, 6, and 29 times respectively, and with an increase the value of 177Lu in quarter step in a cocktail, the amount of the cross dose decrease 3, 15 and 68 percent respectively. CONCLUSION: Generally, the present results indicate that the calculated DPK functions of 177Lu and 90Y cocktails can play an important role in choosing the best combination of radionuclide to optimize treatment planning in cocktail radionuclide therapy.

Assessment of the results and hematological side effects of 3D conformal and IMRT/ARC therapies delivered during craniospinal irradiation of childhood tumors with a follow-up period of five years.

BACKGROUND: Craniospinal irradiation (CSI) of childhood tumors with the RapidArc technique is a new method of treatment. Our objective was to compare the acute hematological toxicity pattern during 3D conformal radiotherapy with the application of the novel technique. METHODS: Data from patients treated between 2007 and 2014 were collected, and seven patients were identified in both treatment groups. After establishing a general linear model, acute blood toxicity results were obtained using SPSS software. Furthermore, the exposure dose of the organs at risk was compared. Patients were followed for a minimum of 5 years, and progression-free survival and overall survival data were assessed. RESULTS: After assessment of the laboratory parameters in the two groups, it may be concluded that no significant differences were detected in terms of the mean dose exposures of the normal tissues or the acute hematological side effects during the IMRT/ARC and 3D conformal treatments. Laboratory parameters decreased significantly compared to the baseline values during the treatment weeks. Nevertheless, no significant differences were detected between the two groups. No remarkable differences were confirmed between the two groups regarding the five-year progression-free survival or overall survival, and no signs of serious organ toxicity due to irradiation were observed during the follow-up period in either of the groups. CONCLUSION: The RapidArc technique can be used safely even in the treatment of childhood tumors, as the extent of the exposure dose in normal tissues and the amount of acute hematological side effects are not higher with this technique.

An Assessment of Radiation Doses From Radon Exposures Using a Mouse Model System.

BACKGROUND: Radon and its progenies contribute significantly to the natural background radiation and cause several thousands of lung cancer cases per year worldwide. Moreover, patients with chronic inflammatory joint diseases are treated in radon galleries. Due to the complex nature of radon exposure, the doses associated with radon exposures are difficult to assess. Hence, there is a clear need to directly measure dose depositions from radon exposures to provide reliable risk estimates for radiation protection guidelines. OBJECTIVES: We aimed to assess tissue-specific radiation doses associated with radon activity concentrations, that deposit similar dose levels as the annual natural radon exposure or radon gallery visits. METHODS: We exposed mice to defined radon concentrations, quantified the number of 53BP1 foci as a measure of induced DNA damage, and compared it with the number of foci induced by known doses of reference-type radiations. An image-based analysis of the 3-dimensional foci pattern provided information about the radiation type inflicting the DNA damage. RESULTS: A 1-hour exposure to 440 kBq/m3 radon-induced DNA damage corresponding to a dose of ∼10 mGy in the lung and ∼3.3 mGy in the kidney, heart, and liver. A 1-hour exposure to 44 kBq/m3 provided values consistent with a linear relationship between dose and radon concentration. Two-thirds of the dose in the lung was caused by α-particles. The dose in the kidney, heart, and liver and one-third of the dose in the lung likely resulted from ß- and γ-rays. DISCUSSION: We found that radon exposures mainly lead to α-particle-induced DNA damage in the lung, consistent with the lung cancer risk obtained in epidemiologic studies. Our presented biodosimetric approach can be used to benchmark risk model calculations for radiation protection guidelines and can help to understand the therapeutic success of radon gallery treatments.

Isotoxic dose prescription level strategies for stereotactic liver radiotherapy: the price of dose uniformity.

Introduction: To find the optimal dose prescription strategy for liver SBRT, this study investigated the tradeoffs between achievable target dose and healthy liver dose for a range of isotoxic uniform and non-uniform prescription level strategies.Material and methods: Nine patients received ten liver SBRT courses with intrafraction motion monitoring during treatment. After treatment, five VMAT treatment plans were made for each treatment course. The PTV margin was 5 mm (left-right, anterior-posterior) and 10 mm (cranio-caudal). All plans had a mean CTV dose of 56.25 Gy in three fractions, while the PTV was covered by 50%, 67%, 67 s% (steep dose gradient outside CTV), 80%, and 95% of this dose, respectively. The 50%, 67 s%, 80%, and 95% plans were then renormalized to be isotoxic with the standard 67% plan according to a Lyman-Kutcher-Burman normal tissue complication probability model for radiation induced liver disease. The CTV D98 and mean dose of the iso-toxic plans were calculated both without and with the observed intrafraction motion, using a validated method for motion-including dose reconstruction.Results: Under isotoxic conditions, the average [range] mean CTV dose per fraction decreased gradually from 21.2 [20.5-22.7] Gy to 15.5 [15.0-16.6] Gy and the D98 dose per fraction decreased from 20.4 [19.7-21.7] Gy to 15.0 [14.5-15.5] Gy, as the prescription level to the PTV rim was increased from 50% to 95%. With inclusion of target motion the mean CTV dose was 20.5 [16.5-22.5] Gy (50% PTV rim dose) and 15.4 [13.9-16.7] Gy (95% rim dose) while D98 was 17.8 [7.4-20.6] Gy (50% rim dose) and 14.6 [8.8-15.7] Gy (95% rim dose).Conclusion: Requirements of a uniform PTV dose come at the price of excess normal tissue dose. A non-uniform PTV dose allows increased CTV mean dose at the cost of robustness toward intrafraction motion. The increase in planned CTV dose by non-uniform prescription outbalanced the dose deterioration caused by motion.

Development and Assessment of Nano-Technologies for Cancer Treatment: Cytotoxicity and Hyperthermia Laboratory Studies.

Cancer treatment by magnetic hyperthermia offers numerous advantages, but for practical applications many variables still need to be adjusted before developing a controlled and reproducible cancer treatment that is bio-compatible (non-damaging) to healthy cells. In this work, Fe3O4 and CoFe2O4 were synthesized and systematically studied for the development of efficient therapeutic agents for applications in hyperthermia. The biocompatibility of the materials was further evaluated using HepG2 cells as biological model. Colorimetric and microscopic techniques were used to evaluate the interaction of magnetic nano-materials (MNMs) and HepG2 cells. Finally, the behavior of MNMs was evaluated under the influence of an alternating magnetic field (AMF), observing a more efficient temperature increment for CoFe2O4, a desirable behavior for biomedical applications since lower doses and shorter expositions to alternating magnetic field might be required.

RETROSPECTIVE ASSESSMENT OF CLINICAL-MORPHOLOGICAL CHANGES OF THE HEPATOBILIARY SYSTEM IN LIVER CIRRHOSIS OF THE CHORNOBYL NPP ACCIDENT CLEAN-UP WORKERS. / RETROSPEKTYVNA OTsINKA KLINIKO-MORFOLOGIChNYKh ZMIN GEPATOBILIARNOÏ SYSTEMY PRY TsYROZI PEChINKY V UChASNYKIV LIKVIDATsIÏ NASLIDKIV ChORNOBYL'S'KOÏ KATASTROFY.

OBJECTIVE: to retrospectively characterize changes in the hepatobiliary system in liver cirrhosis (LC) in the clean-up workers of the Chornobyl NPP accident and to determine the factors of disease progression according to the expert materials of the Central Interagency Expert Commission on Establishing the Causal Relationship of the Diseases with the influence of factors of Chornobyl NPP accident. MATERIALS AND METHODS: Based on the data of 60 cases of the Central Interagency Expert Committee on establishing the causal link of diseases with the impact of the Chornobyl NPP accident, the factors of development, concomitant pathology and indicators of the hepatobiliary system status in 49 deceased and 11 alive clean-up workers with LC were investigated. RESULTS: A retrospective study of the morphological changes of the hepatobiliary system in the clean-up workers with LC showed that the main pathologic anatomical diagnosis in 37.8 % of cases was small-nodal LC, in 8.9 % - micromacronodular, in 4.4 % - large-nodal, in 2.2 % - primary biliary LC, in the other 40 % of cases - LC with uncer- tain nodal structure, as well as 2 (4.4 %) cases of fatty liver and 1 case (2.2 %) of portal cirrhosis against the back- ground of fatty liver. Pathomorphological changes were characterized by expressed growth of fibrous tissue with replacement of the liver parenchyma (fields of fibrosis), increase in size and impaired structure of the liver, thick- ening and tightening of its capsule, fibrotic changes in other organs - gastric mucosa, pancreas, spleen, lungs, heart. Histological examination revealed lobe structure abnormalities, false lobules, periportal fibrosis, lymphoid-lympho- cytic infiltration, diffuse fatty small-sized and large-drop dystrophy, and hepatocyte atrophy. Common inflammato- ry processes and fibrotic changes of other organs and systems: cardiovascular, urinary, bronchopulmonary, stomach, pancreas and spleen made the course of the LC more severe. The most frequent were cardiovascular diseases, signi- ficantly more frequent among the deceased than alive patients: hypertension - 67.3 % and 45.5 %, p < 0.05, coro- nary heart disease - 57.1 % and 18 %, p < 0.05. In most cases, the cause of death in the clean-up workers with LC was hepatic and cellular failure (53.3 %), which together with hepatic-renal failure (17.8 %) made 71.1 %. CONCLUSION: Changes in the hepatobiliary system of change in in the clean-up workers with LC were characterized by marked growth of fibrotic tissue with replacement of the parenchyma and impaired liver structure, fibrotic changes in other organs, diffuse fatty small and large droplet dystrophy and atrophy of hepatocytes. The severe course of the LC with the manifestation of the disease at the stage of decompensation was due to a vague clinical picture, lack of subjective symptoms of liver disease, slow, steadily progressing development, lack of or inadequate examination and treatment, a significant number of concomitant pathology of other organs and systems. The fac- tors of the development of LC in the clean-up workers were the long course of chronic liver disease, numerous con- comitant pathology, long stay in the accident zone, the effect of ionizing radiation, as well as the lack of dispensa- ry supervision and adequate treatment.

Assessment of 3D motion modeling performance for dose accumulation mapping on the MR-linac by simultaneous multislice MRI.

Hybrid MR-linac systems enable intrafraction motion monitoring during radiation therapy. Since time-resolved 3D MRI is still challenging, various motion models have been developed that rely on time-resolved 2D imaging. Continuous validation of these models is important for accurate dose accumulation mapping. In this study we used 2D simultaneous multislice (SMS) imaging to improve the PCA-based motion modeling method developed previously (Stemkens et al 2016 Phys. Med. Biol. 61 5335-55). From the additional simultaneously acquired slices, several independent motion models could be generated, which allowed for an assessment of the sensitivity of the motion model to the location of the time-resolved 2D slices. Additionally, the best model could be chosen at every time-point, increasing the method's robustness. Imaging experiments were performed in six healthy volunteers using three simultaneous slices, which generated three independent models per volunteer. For each model the motion traces of the liver tip and both kidneys were estimated. We found that the location of the 2D slices influenced the model's error in five volunteers significantly with a p -value <0.05, and that selecting the best model at every time-point can improve the method. This allows for more accurate and robust motion characterization in MR-guided radiotherapy.

Exam-level dose monitoring in CT: Quality metric consideration for multiple series acquisitions.

PURPOSE: Multi-series CT examination is common in the clinic, but no metric is agreed upon to report the overall dose from such an examination. This work proposes a relevant metric for tracking patient dose from multi-series examinations and illustrates the evaluation method through explanatory examples. MATERIALS AND METHODS: In each acquisition series, a previously reported method was used to evaluate the cross-sectional average dose along the z-axis of a water phantom, with inputs of CTDIvol , scan length, tube current, and patient water-equivalent diameter. With a multi-series examination, the dose at each z-location was accumulated over all acquisition series. This method was applied to four clinical CT examinations. In three abdominal/pelvic examinations (patient weight, 107, 79, 79 kg), tube current modulation was applied in five acquisition series with scan lengths of 30-41.8 cm, while tube current was fixed in other series with short scan lengths (1.0, 7.9 cm). In another CT-guided liver ablation procedure (patient weight, 114 kg), 22 series were acquired with constant mA and scan lengths of 1-30 cm. The maximum value of the overall dose profile of each examination was compared to five dose quantities, including CTDIvol,sum and SSDEsum by the ACR CT Dose Index Registry, scan length-weighted CTDIvol and SSDE by a CT dose monitoring platform, and "max z location CTDIvol " by a CT manufacturer. RESULTS: A simple graphic display of dose as a function of the z-axis location was presented for each acquisition series and for the whole examination. Differences up to 43.4% and 42.8%, or down to -93.5%, -93.5%, and -49.0%, were observed between the maximum value of the overall dose profile and five dose quantities (in the above order), respectively. CONCLUSION: The overall dose profile gives a complete description of z-axis dose distribution for the studied CT examinations under a wide range of patient variables and acquisition conditions, including multiple acquisition series. Simple visualization of the doses across and beyond the scan ranges may provide a new tool for CT dose optimization.

Comparison of patient dose from routine multi-phase and dynamic liver perfusion CT studies taking into account the effect of iodinated contrast administration.

OBJECTIVES: To accurately determine and compare patient radiation burden from routine multi-phase CT (MPCT) and dynamic CT liver perfusion (CTLP) studies taking into account the effect of iodine uptake of exposed tissues/organs. MATERIALS AND METHODS: 40 consecutive MPCT of upper abdomen and 40 consecutive CTLP studies performed on a modern CT scanner were retrospectively studied. Iodine uptake of radiosensitive tissues at the time of acquisition was calculated through the difference of tissues' CT numbers between NECT and CECT images. Monte Carlo simulation and mathematical anthropomorphic phantoms were employed to derive patient-size-specific organ dose data from each scan involved taking into account the effect of iodinated contrast uptake on absorbed dose. Effective dose estimates were derived for routine multiphase CT and CTLP by summing up the contribution of NECT and CECT scans involved. RESULTS: The mean underestimation error in organ doses from CECT exposures if iodine uptake is not encountered was found to be 2.2%-38.9%. The effective dose to an average-size patient from routine 3-phase CT, 4-phase CT and CTLP studies was found to be 20.6, 27.7 and 25.8 mSv, respectively. Effective dose from CTLP was found lower than 4-phase CT of upper abdomen irrespective of patient body size. Compared to 3-phase CT, the radiation burden from CTLP was found to be higher for average size-patients but again lower for overweight patients. CONCLUSIONS: Modern CT technology allows CTLP studies at comparable or even lower patient radiation burden compared to routine multi-phase liver CT imaging.

Assessment of iterative image reconstruction on kidney and liver donors: Potential role of adaptive iterative dose reduction 3D (AIDR 3D) technology.

OBJECTIVE: The aim of this study was to evaluate the radiation exposure levels in two different types of subjects including liver and kidney donors in diagnostic assessment of transplant operation and also the significance of dose reduction on total effective dose. MATERIALS AND METHODS: A number of Sixty subjects (40 males and 20 females, average age of 35 ± 10 years) were randomly prospectively recruited and equally divided into two distinct groups namely kidney donors (KD, 24 M and 6 F) and liver donors (LD, 21 M and 9 female). Kidney donors were divided into full dose (KFD, n = 20) group and low dose (KLD, n = 10) group. They had undergone dynamic renal scan using Tc99 m-DTPA, CT renal angiography and x-ray plain radiograph. Liver donors were divided into full dose (LFD, n = 20) and low dose (LLD, n = 10) groups and performed CT liver volumetry. The CT dose index (CTDIvol), dose length product (DLP), total milli-ampere product time mAs, effective dose and image noise index were measured in all subjects of kidney and liver donors comparing full dose and low dose protocols. RESULTS: In comparison of all subjects of kidney donor groups (KFD vs KLD), the parameters (mAs = 16386.8 ± 3140.7 vs 2830.286 ± 831.676), (CTDIvol = 183.19 ± 32.58 mGy vs. 45.5 ± 13.3 mGy), DLP = 2884 ± 859.0 mGy.cm vs. 1437.5 ± 399 mGy.cm) and (effective dose = 49.0 ± 9.0 mSv vs. 18.9 mSv±5.7 mSv) were significant, p < 0.0005. Statistical evaluation of liver donors groups (LFD vs LLD) showed that (mAs = 14348.8 ± 4571.8 vs 3123.357 ± 794.5), (CTDIvol = 333.6 ± 59.5 mGy vs. 51.4 ± 13 mGy), (DLP = 3268.3 ± 604.3 mGy.cm vs 1260.5 ± 404.6 mGy.cm) and (effective dose = 43.3 mSv±12.9 mSv vs. 21.6 ± 5.9 mSv) are statistically significant, p < 0.0005. Nevertheless, the comparative evaluation of the image quality noise index of KFD vs KLD groups and LFD vs LLD showed a no statistical significance p > 0.05. CONCLUSION: Renal and liver donors bear a relatively significant radiation dose due to diagnostic evaluation and patient management. The CT iterative reconstruction using AIDR3D proved very valuable tool in dose reduction such that it can reduce 37% in kidney donors and 48% in liver donors while able to maintain an acceptable image quality. Monitoring of those subjects on the clinical and radiobiological levels are recommended.

An analytical dose-averaged LET calculation algorithm considering the off-axis LET enhancement by secondary protons for spot-scanning proton therapy.

PURPOSE: To evaluate the biological effects of proton beams as part of daily clinical routine, fast and accurate calculation of dose-averaged linear energy transfer (LETd ) is required. In this study, we have developed the analytical LETd calculation method based on the pencil-beam algorithm (PBA) considering the off-axis enhancement by secondary protons. This algorithm (PBA-dLET) was then validated using Monte Carlo simulation (MCS) results. METHODS: In PBA-dLET, LET values were assigned separately for each individual dose kernel based on the PBA. For the dose kernel, we employed a triple Gaussian model which consists of the primary component (protons that undergo the multiple Coulomb scattering) and the halo component (protons that undergo inelastic, nonelastic and elastic nuclear reaction); the primary and halo components were represented by a single Gaussian and the sum of two Gaussian distributions, respectively. Although the previous analytical approaches assumed a constant LETd value for the lateral distribution of a pencil beam, the actual LETd increases away from the beam axis, because there are more scattered and therefore lower energy protons with higher stopping powers. To reflect this LETd behavior, we have assumed that the LETs of primary and halo components can take different values (LETp and LEThalo ), which vary only along the depth direction. The values of dual-LET kernels were determined such that the PBA-dLET reproduced the MCS-generated LETd distribution in both small and large fields. These values were generated at intervals of 1 mm in depth for 96 energies from 70.2 to 220 MeV and collected in the look-up table. Finally, we compared the LETd distributions and mean LETd (LETd,mean ) values of targets and organs at risk between PBA-dLET and MCS. Both homogeneous phantom and patient geometries (prostate, liver, and lung cases) were used to validate the present method. RESULTS: In the homogeneous phantom, the LETd profiles obtained by the dual-LET kernels agree well with the MCS results except for the low-dose region in the lateral penumbra, where the actual dose was below 10% of the maximum dose. In the patient geometry, the LETd profiles calculated with the developed method reproduces MCS with the similar accuracy as in the homogeneous phantom. The maximum differences in LETd,mean for each structure between the PBA-dLET and the MCS were 0.06 keV/µm in homogeneous phantoms and 0.08 keV/µm in patient geometries under all tested conditions, respectively. CONCLUSIONS: We confirmed that the dual-LET-kernel model well reproduced the MCS, not only in the homogeneous phantom but also in complex patient geometries. The accuracy of the LETd was largely improved from the single-LET-kernel model, especially at the lateral penumbra. The model is expected to be useful, especially for proper recognition of the risk of side effects when the target is next to critical organs.

Response Assessment by Volumetric Iodine Uptake Measurement: Preliminary Experience in Patients with Intermediate-Advanced Hepatocellular Carcinoma Treated with Yttrium-90 Radioembolization.

PURPOSE: To retrospectively compare early response to yttrium-90 radioembolization (Y90) according to volumetric iodine uptake (VIU) changes, Response Evaluation Criteria In Solid Tumor 1.1 (RECIST 1.1) and modified RECIST (mRECIST) in patients with intermediate-advanced hepatocellular carcinoma (HCC) and to explore their association with survival. MATERIALS AND METHODS: Twenty-four patients treated with Y90 and evaluated with dual-energy computed tomography before and 6 weeks after treatment were included. VIU was measured on late arterial phase spectral images; 6-week VIU response was defined as: complete response (CR, absence of enhancing tumor), partial response (PR, ≥ 15% VIU reduction), progressive disease (PD, ≥ 10% VIU increase) and stable disease (criteria of CR/PR/PD not met). RECIST 1.1 and mRECIST were evaluated at 6 weeks and 6 months. Responders included CR and PR. Overall survival (OS) was evaluated by Kaplan-Meier analysis and compared by Cox regression analysis. RESULTS: High intraobserver and interobserver agreements were observed in VIU measurements (k > 0.98). VIU identified a higher number of responders (18 patients, 75%), compared to RECIST 1.1 (12.5% at 6 weeks and 23.8% at 6 months) and mRECIST (29.2% at 6 weeks and 61.9% at 6 months). There was no significant correlation between OS and RECIST 1.1 (P = 0.45 at 6 weeks; P = 0.21 at 6 months) or mRECIST (P = 0.38 at 6 weeks; P = 0.79 at 6 months); median OS was significantly higher in VIU responders (17.2 months) compared to non-responders (7.4 months) (P = 0.0022; HR 8.85; 95% CI 1.29-88.1). CONCLUSION: VIU is highly reproducible; as opposite to mRECIST and RECIST 1.1, early VIU response correlates with OS after Y90 in intermediate-advanced HCC patients.

The origin and reduction of spurious extrahepatic counts observed in 90Y non-TOF PET imaging post radioembolization.

Our literature survey revealed a physical effect unknown to the nuclear medicine community, i.e. internal bremsstrahlung emission, and also the existence of long energy resolution tails in crystal scintillation. None of these effects has ever been modelled in PET Monte Carlo (MC) simulations. This study investigates whether these two effects could be at the origin of two unexplained observations in 90Y imaging by PET: the increasing tails in the radial profile of true coincidences, and the presence of spurious extrahepatic counts post radioembolization in non-TOF PET and their absence in TOF PET. These spurious extrahepatic counts hamper the microsphere delivery check in liver radioembolization. An acquisition of a 32P vial was performed on a GSO PET system. This is the ideal setup to study the impact of bremsstrahlung x-rays on the true coincidence rate when no positron emission and no crystal radioactivity are present. A MC simulation of the acquisition was performed using Gate-Geant4. MC simulations of non-TOF PET and TOF-PET imaging of a synthetic 90Y human liver radioembolization phantom were also performed. Internal bremsstrahlung and long energy resolution tails inclusion in MC simulations quantitatively predict the increasing tails in the radial profile. In addition, internal bremsstrahlung explains the discrepancy previously observed in bremsstrahlung SPECT between the measure of the 90Y bremsstrahlung spectrum and its simulation with Gate-Geant4. However the spurious extrahepatic counts in non-TOF PET mainly result from the failure of conventional random correction methods in such low count rate studies and poor robustness versus emission-transmission inconsistency. A novel proposed random correction method succeeds in cleaning the spurious extrahepatic counts in non-TOF PET. Two physical effects not considered up to now in nuclear medicine were identified to be at the origin of the unusual 90Y true coincidences radial profile. TOF reconstruction removing of the spurious extrahepatic counts was theoretically explained by a better robustness against emission-transmission inconsistency. A novel random correction method was proposed to overcome the issue in non-TOF PET. Further studies are needed to assess the novel random correction method robustness.

Impact of missing attenuation and scatter corrections on 99m Tc-MAA SPECT 3D dosimetry for liver radioembolization using the patient relative calibration methodology: A retrospective investigation on clinical images.

PURPOSE: To investigate the clinical implication of performing pre-treatment dosimetry for 90 Y-microspheres liver radioembolization on 99m Tc-MAA SPECT images reconstructed without attenuation or scatter correction and quantified with the patient relative calibration methodology. METHODS: Twenty-five patients treated with SIR-Spheres® at Istituto Europeo di Oncologia and 31 patients treated with TheraSphere® at Istituto Nazionale Tumori were considered. For each acquired 99m Tc-MAA SPECT, four reconstructions were performed: with attenuation and scatter correction (AC_SC), only attenuation (AC_NoSC), only scatter (NoAC_SC) and without corrections (NoAC_NoSC). Absorbed dose maps were calculated from the activity maps, quantified applying the patient relative calibration to the SPECT images. Whole Liver (WL) and Tumor (T) regions were drawn on CT images. Injected Liver (IL) region was defined including the voxels receiving absorbed dose >3.8 Gy/GBq. Whole Healthy Liver (WHL) and Healthy Injected Liver (HIL) regions were obtained as WHL = WL - T and HIL = IL - T. Average absorbed dose to WHL and HIL were calculated, and the injection activity was derived following each Institute's procedure. The values obtained from AC_NoSC, NoAC_SC and NoAC_NoSC images were compared to the reference value suggested by AC_SC images using Bland-Altman analysis and Wilcoxon paired test (5% significance threshold). Absorbed-dose maps were compared to the reference map (AC_SC) in global terms using the Voxel Normalized Mean Square Error (%VNMSE), and at voxel level by calculating for each voxel the normalized difference with the reference value. The uncertainty affecting absorbed dose at voxel level was accounted for in the comparison; to this purpose, the voxel counts fluctuation due to Poisson and reconstruction noise was estimated from SPECT images of a water phantom acquired and reconstructed as patient images. RESULTS: NoAC_SC images lead to activity prescriptions not significantly different from the reference AC_SC images; the individual differences (<0.1 GBq for all IEO patients, <0.6 GBq for all but one INT patients) were comparable to the uncertainty affecting activity measurement. AC_NoSC and NoAC_NoSC images, instead, yielded significantly different activity prescriptions and wider 95% confidence intervals in the Bland-Altman analysis. Concerning the absorbed dose map, AC_NoSC images had the smallest %VNMSE value and the highest fraction of voxels differing less than 2 standard deviations from AC_SC. CONCLUSIONS: The patient relative calibration methodology can compensate for the missing attenuation correction when performing healthy liver pre-treatment dosimetry: safe treatments can be planned even on NoAC_SC images, suggesting activities comparable to AC_SC images. Scatter correction is recommended due to its heavy impact on healthy liver dosimetry.

Feasibility assessment of yttrium-90 liver radioembolization imaging using amplitude-based gated PET/CT.

PURPOSE: The usage of PET/computed tomography (CT) to monitor hepatocellular carcinoma patients following yttrium-90 (Y) radioembolization has increased. Respiratory motion causes liver movement, which can be corrected using gating techniques at the expense of added noise. This work examines the use of amplitude-based gating on Y-PET/CT and its potential impact on diagnostic integrity. PATIENTS AND METHODS: Patients were imaged using PET/CT following Y radioembolization. A respiratory band was used to collect respiratory cycle data. Patient data were processed as both standard and motion-corrected images. Regions of interest were drawn and compared using three methods. Activity concentrations were calculated and converted into dose estimates using previously determined and published scaling factors. Diagnostic assessments were performed using a binary scale created from published Y-PET/CT image interpretation guidelines. RESULTS: Estimates of radiation dose were increased (P<0.05) when using amplitude-gating methods with Y PET/CT imaging. Motion-corrected images show increased noise, but the diagnostic determination of success, using the Kao criteria, did not change between static and motion-corrected data. CONCLUSION: Amplitude-gated PET/CT following Y radioembolization is feasible and may improve Y dose estimates while maintaining diagnostic assessment integrity.

Characterization of 90 Y-SPECT/CT self-calibration approaches on the quantification of voxel-level absorbed doses following 90 Y-microsphere selective internal radiation therapy.

PURPOSE: 90 Y-microsphere selective internal radiation therapy (90 Y-SIRT or 90 Y-radioembolization) is used in the management of unresectable liver tumors. 90 Y-SIRT presents a unique situation where the total 90 Y activity inside the liver can be determined with high accuracy (> 95%). 90 Y bremsstrahlung single-photon emission computed tomography (SPECT)/computed tomography (CT) can be self-calibrated to provide quantitative images that facilitate voxel-level absorbed dose calculations. We investigated the effects of different approaches for 90 Y-SPECT self-calibration on the quantification of absorbed doses following 90 Y-SIRT. METHODS: 90 Y bremsstrahlung SPECT/CT images of 31 patients with hepatocellular carcinoma, collected following 90 Y-SIRT, were analyzed, yielding 48 tumor and 31 normal liver contours. We validated the accuracy of absorbed doses calculated by a commercial software against those calculated using Monte Carlo-based radiation transport. The software package was used to analyze the following definitions of SPECT volume of interest used for 90 Y-SPECT self-calibration: (a) SPECT field-of-view (FOV), (b) chest-abdomen contour, (c) total liver contour, (d) total liver contour expanded by 5 mm, and (e) total liver contour contracted by 5 mm. Linear correlation and Bland-Altman analysis were performed for tumor and normal liver tissue absorbed dose volume histogram metrics between the five different approaches for 90 Y-SPECT self-calibration. RESULTS: The mean dose calculated using the commercial software was within 3% of Monte Carlo for tumors and normal liver tissues. The tumor mean dose calculated using the chest-abdomen calibration was within 2% of that calculated using the SPECT FOV, whereas the doses calculated using the total liver contour, expanded total liver contour, and contracted total liver contour were within 68%, 47%, and 107%, respectively, of doses calculated using the SPECT FOV. The normal liver tissue mean dose calculated using the chest-abdomen contour was within 1.3% of that calculated using the SPECT FOV, whereas the doses calculated using the total liver contour, expanded total liver contour, and contracted total liver contour were within 73%, 50%, and 114%, respectively, of doses calculated using the SPECT FOV. CONCLUSIONS: The mean error of < 3% for commercial software can be considered clinically acceptable for 90 Y-SIRT dosimetry. Absorbed dose quantification using 90 Y-SPECT self-calibration with the chest-abdomen contour was equivalent to that calculated using the SPECT FOV, but self-calibration with the total liver contour yielded substantially higher (~70%) dose values. The large biases revealed by our study suggest that consistent absorbed dose calculation approaches are essential when comparing 90 Y-SIRT dosimetry between different clinical studies.

Challenges in imaging assessment following liver stereotactic body radiotherapy: pitfalls to avoid in clinical practice.

Stereotactic body radiotherapy (SBRT) is increasingly used in the management of unresectable liver metastases and hepatocellular carcinoma (HCC) as it allows delivery of high-dose conformal radiotherapy with limited toxicities. However, it may be difficult to differentiate viable tumour from radiotherapy-related changes after SBRT. The imaging changes observed after SBRT may also differ from those observed following conventionally fractionated radiotherapy. Hence, we aim to review the imaging changes that occur within the tumour and adjacent normal liver after SBRT which may help to identify local relapse in clinical practice.

Modulation of lateral positions of Bragg peaks via magnetic fields inside cancer patients: Toward magnetic field modulated proton therapy.

PURPOSE: This work investigated whether the Bragg peak (BP) positions of proton beams can be modulated to produce uniform doses and cover a tumor under the magnetic fields inside cancer patients, and whether magnetic field modulated proton therapy (MMPT) is effective in vital organ protection. METHODS: The authors initially constructed an ideal water phantom comprising a central tumor surrounded by cuboid organ regions using GEANT4. Second, we designed the proton beams passing through the gap between two adjacent organ regions during beam configuration. Third, we simulated the beam transports under magnetic fields inside the phantom through GEANT4. Then, the beams were discarded, which did not stop in the tumor. Fourth, the authors modulated the intensities of the remaining beams to produce uniform tumor doses. Subsequently, the calculated MMPT doses were compared with those of traditional methods, such as single, opposing, orthogonal, and box fields. Moreover, the authors repeated the above research procedures for abdominal anatomies comprising tumors at the pancreatic tail and liver to evaluate whether MMPT is effective for the human anatomy. RESULTS: For the water phantom, the vital organ doses were approximately 50%, 30%, 30%, and 15% for the single, opposing, orthogonal, and box fields, respectively. As the vital organ doses decreased, the organ volume receiving proton irradiations for the opposing, orthogonal, and box fields increased by two, two, and four times compared with that for the single field. The vital organ volume receiving proton irradiations were controlled to a fairly low level through MMPT, whereas the BP positions of the proton beams were properly modulated through the magnetic fields inside the phantom. The tumor was sufficiently covered by a 95% dose line, and the maximum tumor doses were smaller than 110%. For the pancreatic tumor case, the proton beams were curved and bypassed the kidney to generate uniform doses inside the tumor through MMPT. In the liver tumor case, the liver volume receiving proton irradiations was reduced by approximately 40% through MMPT compared with traditional methods. CONCLUSIONS: The BP positions can be intentionally modulated to produce uniform tumor doses under the magnetic fields inside cancer patients. In some special cases, the vital organs surrounding the tumor can almost be exempted from proton irradiations without sacrificing tumor dose coverage through MMPT. For the tumors inside parallel organs, the parallel organ volume receiving proton irradiations was largely reduced through MMPT. The results of this study can serve as beneficial implications for future proton therapy studies with reduced vital organ damage and complications.

Computational modeling of 915 MHz microwave ablation: Comparative assessment of temperature-dependent tissue dielectric models.

PURPOSE: The objective of this study is to develop a computational model for simulating 915 MHz microwave ablation (MWA), and verify the simulation predictions of transient temperature profiles against experimental measurements. Due to the limited experimental data characterizing temperature-dependent changes of tissue dielectric properties at 915 MHz, we comparatively assess two temperature-dependent approaches of modeling of dielectric properties: model A- piecewise linear temperature dependencies based on existing, but limited, experimental data, and model B- similar to model A, but augmented with linear decrease in electrical conductivity above 95 °C, as guided by our experimental measurements. METHODS: The finite element method was used to simulate MWA procedures in liver with a clinical 915 MHz ablation applicator. A coupled electromagnetic-thermal solver incorporating temperature-dependent tissue biophysical properties of liver was implemented. Predictions of the transient temperature profiles and ablation zone dimensions for both model A and model B were compared against experimental measurements in ex vivo bovine liver tissue. Broadband dielectric properties of tissue within different regions of the ablation zone were measured and reported at 915 MHz and 2.45 GHz. RESULTS: Model B yielded peak tissue temperatures in closer agreement with experimental measurements, attributed to the inclusion of decrease in electrical conductivity at elevated temperature. The simulated transverse diameters of the ablation zone predicted by both models were greater than experimental measurements, which may be in part due to the lack of a tissue shrinkage model. At both considered power levels, predictions of transverse ablation zone diameters were in closer agreement with measurements for model B (max. discrepancy of 5 mm at 60 W, and 3 mm at 30 W), compared to model A (max. discrepancy of 9 mm at 60 W, and 6 mm at 30 W). Ablation zone lengths with both models were within 2 mm at 30 W, but overestimated by up to 10 mm at 60 W. CONCLUSIONS: The inclusion of decreased electrical conductivity above 95 °C, implemented with model B as guided by our experimental measurements, may be a good approach for approximating the dynamic changes that occur during MWA at 915 MHz. Although a step toward more effectively modeling MWA at 915 MHz, further investigation of the transition in dielectric properties with temperature and tissue shrinkage, especially at high temperatures is needed for more accurate simulations.