Marker-controlled watershed with deep edge emphasis and optimized H-minima transform for automatic segmentation of densely cultivated 3D cell nuclei.

BACKGROUND: The segmentation of 3D cell nuclei is essential in many tasks, such as targeted molecular radiotherapies (MRT) for metastatic tumours, toxicity screening, and the observation of proliferating cells. In recent years, one popular method for automatic segmentation of nuclei has been deep learning enhanced marker-controlled watershed transform. In this method, convolutional neural networks (CNNs) have been used to create nuclei masks and markers, and the watershed algorithm for the instance segmentation. We studied whether this method could be improved for the segmentation of densely cultivated 3D nuclei via developing multiple system configurations in which we studied the effect of edge emphasizing CNNs, and optimized H-minima transform for mask and marker generation, respectively. RESULTS: The dataset used for training and evaluation consisted of twelve in vitro cultivated densely packed 3D human carcinoma cell spheroids imaged using a confocal microscope. With this dataset, the evaluation was performed using a cross-validation scheme. In addition, four independent datasets were used for evaluation. The datasets were resampled near isotropic for our experiments. The baseline deep learning enhanced marker-controlled watershed obtained an average of 0.69 Panoptic Quality (PQ) and 0.66 Aggregated Jaccard Index (AJI) over the twelve spheroids. Using a system configuration, which was otherwise the same but used 3D-based edge emphasizing CNNs and optimized H-minima transform, the scores increased to 0.76 and 0.77, respectively. When using the independent datasets for evaluation, the best performing system configuration was shown to outperform or equal the baseline and a set of well-known cell segmentation approaches. CONCLUSIONS: The use of edge emphasizing U-Nets and optimized H-minima transform can improve the marker-controlled watershed transform for segmentation of densely cultivated 3D cell nuclei. A novel dataset of twelve spheroids was introduced to the public.

Pretargeted PET Imaging with a TCO-Conjugated Anti-CD44v6 Chimeric mAb U36 and [89Zr]Zr-DFO-PEG5-Tz.

The recent advances in the production of engineered antibodies have facilitated the development and application of tailored, target-specific antibodies. Positron emission tomography (PET) of these antibody-based drug candidates can help to better understand their in vivo behavior. In this study, we report an in vivo proof-of-concept pretargeted immuno-PET study where we compare a pretargeting vs targeted approach using a new 89Zr-labeled tetrazine as a bio-orthogonal ligand in an inverse electron demand Diels-Alder (IEDDA) in vivo click reaction. A CD44v6-selective chimeric monoclonal U36 was selected as the targeting antibody because it has potential in immuno-PET imaging of head-and-neck squamous cell carcinoma (HNSCC). Zirconium-89 (t1/2 = 78.41 h) was selected as the radionuclide of choice to be able to make a head-to-head comparison of the pretargeted and targeted approaches. [89Zr]Zr-DFO-PEG5-Tz ([89Zr]Zr-3) was synthesized and used in pretargeted PET imaging of HNSCC xenografts (VU-SCC-OE) at 24 and 48 h after administration of a trans-cyclooctene (TCO)-functionalized U36. The pretargeted approach resulted in lower absolute tumor uptake than the targeted approach (1.5 ± 0.2 vs 17.1 ± 3.0% ID/g at 72 h p.i. U36) but with comparable tumor-to-non-target tissue ratios and significantly lower absorbed doses. In conclusion, anti-CD44v6 monoclonal antibody U36 was successfully used for 89Zr-immuno-PET imaging of HNSCC xenograft tumors using both a targeted and pretargeted approach. The results not only support the utility of the pretargeted approach in immuno-PET imaging but also demonstrate the challenges in achieving optimal in vivo IEDDA reaction efficiencies in relation to antibody pharmacokinetics.

Intravitreal Pharmacokinetics in Mice: SPECT/CT Imaging and Scaling to Rabbits and Humans.

Preclinical in vivo tests of retinal drug responses are carried out in mice and rats, often after intravitreal injections. However, quantitative pharmacokinetics in the mouse eye is poorly understood. Ocular pharmacokinetics studies are usually done in rabbits. We investigated elimination of three compounds ([99mTc]Tc-pentetate, [111In]In-pentetreotide, [99mTc]Tc-human serum albumin with molecular weights of 510.2 Da, 1506.4 Da, and 66.5 kDa, respectively) from mouse vitreous using imaging with single photon emission computed tomography/computed tomography (SPECT/CT). Increasing molecular weight decreased elimination of the compounds from the mouse eyes. Half-lives of [99mTc]Tc-pentetate, [111In]In-pentetreotide, and [99mTc]Tc-human serum albumin in the mouse eyes were 1.8 ± 0.5 h, 4.3 ± 1.7 h, and 30.0 ± 9.0 h, respectively. These values are 3-12-fold shorter than half-lives of similar compounds in the rabbit vitreous. Dose scaling factors were calculated for mouse-to-rabbit and mouse-to-man translation. They were 27-90 and 38-126, respectively, for intravitreal injections in rabbit and man. We show ocular pharmacokinetic parameters for mice and interspecies scaling factors that may augment ocular drug discovery and development.

Effect of calculation method on kidney dosimetry in 177Lu-octreotate treatment.

BACKGROUND: 177Lu-octreotate is an effective treatment modality for patients with metastatic neuroendocrine tumors. The kidney is a critical dose-limiting organ in that modality. We investigated the absorbed doses in the kidney and compared whole kidney volume (WKV) and small (4 cm3) volume of the kidney (SV) methods. We also evaluated a new calculation method that was based on two single photon emission computed tomography/computed tomography (SPECT/CT) scans. METHODS: Absorbed radiation doses in the kidneys were calculated for 24 patients with neuroendocrine tumors. All patients received four cycles of 177Lu-octreotate given at eight-week intervals with a mean activity of 7.1 GBq (range 3.28-8.79 GBq). Absorbed doses and half-lives were calculated by the WKV and SV methods. Dosimetry was determined for the cortex and medulla in the first treatment cycle. RESULTS: The mean absorbed radiation dose was 0.44 ± 0.15 Gy/GBq for the WKV method and, 0.74 ± 0.28 Gy/GBq for the SV method. Three patients had a 20% increase of the absorbed dose over the four treatment cycles for the WKV method compared to eight patients for the SV method. The mean absorbed dose in the medulla was 0.62 ± 0.27 Gy/GBq, whereas the mean absorbed dose in the cortex was 0.41 ± 0.22 Gy/GBq. Both regions had similar half-lives. Patients who received lower activities for medical reasons still had similar absorbed doses to kidneys compared to those who received the full activities. Our study indicates that absorbed doses can be calculated reliably using two SPECT/CT scans, at 24 and 168 hours after each treatment. CONCLUSIONS: Absorbed doses in the kidneys from systemic radionuclide therapy that are measured by the WKV method and SV method cannot be directly compared. There were regional differences within kidneys for the uptake of 177Lu-octreotate. Two SPECT/CTs are sufficient for kidney dosimetry based on our new calculation method.

Time-Activity data fitting in molecular Radiotherapy: Methodology and pitfalls.

Absorbed radiation doses are essential in assessing the effects, e.g. safety and efficacy, of radiopharmaceutical therapy (RPT). Patient-specific absorbed dose calculations in the target or the organ at risk require multiple inputs. These include the number of disintegrations in the organ, i.e. the time-integrated activities (TIAs) of the organs, as well as other parameters describing the process of radiation energy deposition in the target tissue (i.e. mean energy per disintegration, radiation dose constants, etc). TIAs are then estimated by incorporating the area under the radiopharmaceutical's time-activity curve (TAC), which can be obtained by quantitative measurements of the biokinetics in the patient (typically based on imaging data such as planar scintigraphy, SPECT/CT, PET/CT, or blood and urine samples). The process of TAC determination/calculation for RPT generally depends on the user, e.g., the chosen number and schedule of measured time points, the selection of the fit function, the error model for the data and the fit algorithm. These decisions can strongly affect the final TIA values and thus the accuracy of calculated absorbed doses. Despite the high clinical importance of the TIA values, there is currently no consensus on processing time-activity data or even a clear understanding of the influence of uncertainties and variations in personalised RPT dosimetry related to user-dependent TAC calculation. As a first step towards minimising site-dependent variability in RPT dosimetry, this work provides an overview of quality assurance and uncertainty management considerations of the TIA estimation.

Adenosine-induced splenic switch-off on [15O]H2O PET perfusion for the assessment of vascular vasodilatation.

BACKGROUND: Splenic switch-off (SSO) is a marker of adequate adenosine-induced vasodilatation on cardiac magnetic resonance perfusion imaging. We evaluate the feasibility of quantitative assessment of SSO in myocardial positron emission tomography (PET) perfusion imaging using [15O]H2O. METHODS: Thirty patients underwent [15O]H2O PET perfusion with adenosine stress. Time-activity curves, as averaged standardized uptake values (SUVavg), were extracted from dynamic PET for spleen and liver. Maximum SUVavg, stress and rest spleen-to-liver ratio (SLR), and the splenic activity concentration ratio (SAR) were computed. Optimal cut-off values for SSO assessment were estimated from receiver operating characteristics (ROC) curve for maximum SUVavg and SLR. Also, differences between coronary artery disease, myocardial ischemia, beta-blockers, and diabetes were assessed. Data are presented as median [interquartile range]. RESULTS: In concordance with the SSO phenomenon, both the spleen maximum SUVavg and SLR were lower in adenosine stress when compared to rest perfusion (8.1 [6.5, 9.2] versus 16.4 [13.4, 19.0], p < 0.001) and (0.81 [0.63, 1.08] versus 1.86 [1.73, 2.06], p < 0.001), respectively. During adenosine stress, the SSO effect was most prominent 40-160 s after radiotracer injection. Cut-off values of 12.6 and 1.57 for maximum SUVavg and SLR, respectively, were found based on ROC analysis. No differences in SAR, SLRRest, or SLRStress were observed in patients with coronary artery disease, myocardial ischemia, or diabetes. CONCLUSIONS: SSO can be quantified from [15O]H2O PET perfusion and used as a marker for adequate adenosine-induced vasodilatation response. In contrary to other PET perfusion tracers, adenosine-induced SSO is time dependent with [15O]H2O.

Accuracy of the electron transport in mcnp5 and its suitability for ionization chamber response simulations: A comparison with the egsnrc and penelope codes.

PURPOSE: In this work, accuracy of the mcnp5 code in the electron transport calculations and its suitability for ionization chamber (IC) response simulations in photon beams are studied in comparison to egsnrc and penelope codes. METHODS: The electron transport is studied by comparing the depth dose distributions in a water phantom subdivided into thin layers using incident energies (0.05, 0.1, 1, and 10 MeV) for the broad parallel electron beams. The IC response simulations are studied in water phantom in three dosimetric gas materials (air, argon, and methane based tissue equivalent gas) for photon beams ((60)Co source, 6 MV linear medical accelerator, and mono-energetic 2 MeV photon source). Two optional electron transport models of mcnp5 are evaluated: the ITS-based electron energy indexing (mcnp5(ITS)) and the new detailed electron energy-loss straggling logic (mcnp5(new)). The electron substep length (ESTEP parameter) dependency in mcnp5 is investigated as well. RESULTS: For the electron beam studies, large discrepancies (>3%) are observed between the MCNP5 dose distributions and the reference codes at 1 MeV and lower energies. The discrepancy is especially notable for 0.1 and 0.05 MeV electron beams. The boundary crossing artifacts, which are well known for the mcnp5(ITS), are observed for the mcnp5(new) only at 0.1 and 0.05 MeV beam energies. If the excessive boundary crossing is eliminated by using single scoring cells, the mcnp5(ITS) provides dose distributions that agree better with the reference codes than mcnp5(new). The mcnp5 dose estimates for the gas cavity agree within 1% with the reference codes, if the mcnp5(ITS) is applied or electron substep length is set adequately for the gas in the cavity using the mcnp5(new). The mcnp5(new) results are found highly dependent on the chosen electron substep length and might lead up to 15% underestimation of the absorbed dose. CONCLUSIONS: Since the mcnp5 electron transport calculations are not accurate at all energies and in every medium by general clinical standards, caution is needed, if mcnp5 is used with the current electron transport models for dosimetric applications.

Convolutional neural networks for detection of transthyretin amyloidosis in 2D scintigraphy images.

BACKGROUND: Transthyretin amyloidosis (ATTR) is a progressive disease which can be diagnosed non-invasively using bone avid [99mTc]-labeled radiotracers. Thus, ATTR is also an occasional incidental finding on bone scintigraphy. In this study, we trained convolutional neural networks (CNN) to automatically detect and classify ATTR from scintigraphy images. The study population consisted of 1334 patients who underwent [99mTc]-labeled hydroxymethylene diphosphonate (HMDP) scintigraphy and were visually graded using Perugini grades (grades 0-3). A total of 47 patients had visual grade ≥ 2 which was considered positive for ATTR. Two custom-made CNN architectures were trained to discriminate between the four Perugini grades of cardiac uptake. The classification performance was compared to four state-of-the-art CNN models. RESULTS: Our CNN models performed better than, or equally well as, the state-of-the-art models in detection and classification of cardiac uptake. Both models achieved area under the curve (AUC) ≥ 0.85 in the four-class Perugini grade classification. Accuracy was good in detection of negative vs. positive ATTR patients (grade < 2 vs grade ≥ 2, AUC > 0.88) and high-grade cardiac uptake vs. other patients (grade < 3 vs. grade 3, AUC = 0.94). Maximum activation maps demonstrated that the automated deep learning models were focused on detecting the myocardium and not extracardiac features. CONCLUSION: Automated convolutional neural networks can accurately detect and classify different grades of cardiac uptake on bone scintigraphy. The CNN models are focused on clinically relevant image features. Automated screening of bone scintigraphy images using CNN could improve the early diagnosis of ATTR.

Quantitative Monte Carlo-based brain dopamine transporter SPECT imaging.

OBJECTIVE: Brain dopamine transporter imaging with I-123-labeled radioligands is technically demanding due to the small size of the imaging target relative to the spatial resolution of most SPECT systems. In addition, I-123 has high-energy peaks which can penetrate or scatter in the collimator and be detected in the imaging energy window. The aim of this study was to implement Monte Carlo (MC)-based full collimator-detector response (CDR) compensation algorithm for I-123 into a third-party commercial SPECT reconstruction software package and to evaluate its effect on the quantitative accuracy of dopaminergic-image analysis compared to a method where only the geometric component of the CDR is compensated. METHODS: In this work, we utilized a full Monte Carlo collimator-detector model and incorporated it into an iterative SPECT reconstruction algorithm. The full Monte Carlo model reconstruction was compared to standard reconstruction using an anthropomorphic striatal phantom filled with different I-123 striatal/cortex uptake ratios and with clinical I-123 Ioflupane DaTScan studies. RESULTS: Reconstruction with the full model yielded higher (13-25%) striatal uptake ratios than the conventional reconstruction, but the uptake ratios were still much lower than the true ratios due to partial volume effect. Visually, images reconstructed with the full Monte Carlo model had better contrast and resolution than the conventional images, with both phantom and patient studies. CONCLUSIONS: Reconstruction with full Monte Carlo collimator-detector model yields higher quantitative accuracy than conventional reconstruction. Additional work to reduce the partial volume effect related errors would improve the accuracy further.

Estimation of absorbed radiation doses to skin and S-values for organs at risk due to nasal administration of PET agents using Monte Carlo simulations.

PURPOSE: The intranasal (IN) administration of radiopharmaceuticals is of interest in being a viable route for the delivery of radiopharmaceuticals that do not ordinarily cross the blood-brain barrier (BBB). However, to be viable in a patient population, good image quality as well as safety of the administration should be demonstrated. This work provides radiation dosimetry calculations and simulations related to the radiation safety of performing such experiments in a human cohort. METHODS: We performed Monte Carlo (MC) simulations to estimate radiation dose to the skin inside a cylindrical model of the nasal cavity assuming a homogenous distribution layer of 11 C and 18 F and calculated a geometry conversion factor (FP-C ) which can be used to convert from a planar geometry to a cylindrical geometry using more widely available software tools. We compared radiation doses from our simulated cylindrical geometry with the planar dose estimates employing our geometry conversion factor from VARSKIN 6.1 software and also from an analytical equation. Furthermore, in order to estimate radiation dosimetry to surrounding organs of interest, we performed a voxelized MC simulation of a fixed radioactivity inside the nasal cavity and calculated S-values to organs such as the eyes, thyroid, and brain. RESULTS: MC simulations of contamination scenarios using planar absorbed doses of 15.50 and 8.60 mGy/MBq for 18 F and 11 C, respectively, and 35.70 and 19.80 mGy/MBq per hour for cylindrical geometries, leading to determination of an FP-C of 2.3. Planar absorbed doses (also in units of mGy/MBq) determined by the analytical equation were 16.96 and 8.68 (18 F and 11 C) and using VARSKIN were 16.60 and 9.26 (18 F and 11 C), respectively. Application of FP-C to these results demonstrates values with a maximum difference of 9.41% from the cylindrical geometry MC calculation, demonstrating that when accounting for geometry, more simplistic techniques can be utilized to estimate IN dosimetry. Voxelized MC simulations of radiation dosimetry from a fixed source of 1 MBq of activity confined to the nasal cavity resulted in S-values to the thyroid, eyes, and brain of 1.72 x 10-6 , 1.93 x 10-5 , and 3.51 x 10-6  mGy/MBq·s, respectively, for 18 F and 1.80 × 10-6 , 1.95 × 10-5 , and 3.54 × 10-6  mGy/MBq·s for 11 C. CONCLUSION: Dosimetry concerns about IN administrations of PET radiotracers should be considered before clinical use. Values presented in the simulations such as the S-values can be further used for assessment of absorbed doses in cases of IN administration, and can be used to develop and adapt specific study protocols. All three presented methods provided similar results when considering the use of a geometry conversion factor for planar to cylindrical geometry, demonstrating that standard tools rather than dedicate MC simulations may be used to perform dose calculations in nasal administrations.

Assessment of ejection fraction and heart perfusion using myocardial perfusion single-photon emission computed tomography in Finland and Estonia: a multicenter phantom study.

OBJECTIVES: Myocardial SPECT/CT imaging is frequently performed to assess myocardial perfusion and dynamic parameters of heart function, such as ejection fraction (EF). However, potential pitfalls exist in the imaging chain that can unfavorably affect diagnosis and treatment. We performed a national cardiac quality control study to investigate how much SPECT/CT protocols vary between different nuclear medicine units in Finland, and how this may affect the heart perfusion and EF values. METHODS: Altogether, 21 nuclear medicine units participated with 27 traditional SPECT/CT systems and two cardiac-centered IQ-SPECT systems. The reproducibility of EF and the uniformity of perfusion were studied using a commercial dynamic heart phantom. SPECT/CT acquisitions were performed and processed at each participating unit using their own clinical protocol and with a standardized protocol. The effects of acquisition protocols and analysis routines on EF estimates and uniformity of perfusion were studied. RESULTS: Considerable variation in EF estimates and in the uniformity of perfusion were observed between the units. Uniformity of perfusion was improved in some units after applying the higher count-statistic standard acquisition protocol. EF estimates varied more due to differences in analysis routines than as a result of different acquisition protocols. The results obtained with the two IQ-SPECT systems differed substantially from the traditional multipurpose cameras. CONCLUSION: On average, the EF and heart perfusion were accurately estimated by SPECT/CT, but high errors could be produced if the acquisition and analysis routines were poorly optimized. Eight of the 21 participants altered their imaging protocol after this quality control tour.

A Nordic survey of CT doses in hybrid PET/CT and SPECT/CT examinations.

BACKGROUND: Computed tomography (CT) scans are routinely performed in positron emission tomography (PET) and single photon emission computed tomography (SPECT) examinations globally, yet few surveys have been conducted to gather national diagnostic reference level (NDRL) data for CT radiation doses in positron emission tomography/computed tomography (PET/CT) and single photon emission computed tomography/computed tomography (SPECT/CT). In this first Nordic-wide study of CT doses in hybrid imaging, Nordic NDRL CT doses are suggested for PET/CT and SPECT/CT examinations specific to the clinical purpose of CT, and the scope for optimisation is evaluated. Data on hybrid imaging CT exposures and clinical purpose of CT were gathered for 5 PET/CT and 8 SPECT/CT examinations via designed booklet. For each included dataset for a given facility and scanner type, the computed tomography dose index by volume (CTDIvol) and dose length product (DLP) was interpolated for a 75-kg person (referred to as CTDIvol,75kg and DLP75kg). Suggested NDRL (75th percentile) and achievable doses (50th percentile) were determined for CTDIvol,75kg and DLP75kg according to clinical purpose of CT. Differences in maximum and minimum doses (derived for a 75-kg patient) between facilities were also calculated for each examination and clinical purpose. RESULTS: Data were processed from 83 scanners from 43 facilities. Data were sufficient to suggest Nordic NDRL CT doses for the following: PET/CT oncology (localisation/characterisation, 15 systems); infection/inflammation (localisation/characterisation, 13 systems); brain (attenuation correction (AC) only, 11 systems); cardiac PET/CT and SPECT/CT (AC only, 30 systems); SPECT/CT lung (localisation/characterisation, 12 systems); bone (localisation/characterisation, 30 systems); and parathyroid (localisation/characterisation, 13 systems). Great variations in dose were seen for all aforementioned examinations. Greatest differences in DLP75kg for each examination, specific to clinical purpose, were as follows: SPECT/CT lung AC only (27.4); PET/CT and SPECT/CT cardiac AC only (19.6); infection/inflammation AC only (18.1); PET/CT brain localisation/characterisation (16.8); SPECT/CT bone localisation/characterisation (10.0); PET/CT oncology AC only (9.0); and SPECT/CT parathyroid localisation/characterisation (7.8). CONCLUSIONS: Suggested Nordic NDRL CT doses are presented according to clinical purpose of CT for PET/CT oncology, infection/inflammation, brain, PET/CT and SPECT/CT cardiac, and SPECT/CT lung, bone, and parathyroid. The large variation in doses suggests great scope for optimisation in all 8 examinations.

Heterogeneity of myocardial 2-[18F]fluoro-2-deoxy-D-glucose uptake is a typical feature in cardiac sarcoidosis: a study of 231 patients.

Aims: The goal of the investigation was to evaluate whether a semi-quantitative method reflecting myocardial 2-[18F]fluoro-2-deoxy-D-glucose (FDG) uptake heterogeneity has added value in addition to visual analysis in the diagnosis of cardiac sarcoidosis (CS). Methods and results: This retrospective analysis included 271 consecutive patients suspected of CS attending cardiac positron emission tomography combined with computed tomography (PET-CT) at our institution between 2007 and 2013. Visual analysis of PET-CT and semi-quantitative analysis of heterogeneity [coefficient of variation (CoV)] of myocardial FDG uptake were performed. The presence of CS and initial symptoms were verified from patient data. The criteria for CS included histological verification from the myocardium or from an extracardiac site. Thirty cancer patients without cardiac disease were included as controls. CS was diagnosed in 48/231 (20.8%) of analysed patients. Of these, 13 (27.1%) had no extracardial signs of the disease and 30 (62.5%) had FDG positive mediastinal lymph nodes. Visual analysis of PET-CT identified 48.9% of the CS patients. We found a cut-off value of 0.184 for CoV to have the best accuracy to detect CS from a patient population with suspected CS (75.0% sensitivity and 51.4% specificity). Compared to controls, CoV identified CS patients with a good accuracy (68.8% sensitivity and 93.3% specificity). CS patients with FDG positive mediastinal lymph nodes had higher CoV than CS patients without lymph node involvement (0.282 vs. 0.208, P = 0.016). CS patients with more severe initial symptoms had a higher CoV than patients with more benign symptoms (0.283 vs. 0.195, P = 0.01). Conclusion: CoV provides a good addition to visual analysis of cardiac FDG PET-CT in diagnosis of CS. As a semi-quantitative measure, it reduces intra-observer variability. It also seems to indicate more severe disease, but to confirm this, prospective studies are needed.

Phantom and clinical evaluation of the effect of full Monte Carlo collimator modelling in post-SIRT yttrium-90 Bremsstrahlung SPECT imaging.

BACKGROUND: Post-therapy SPECT/CT imaging of 90Y microspheres delivered to hepatic malignancies is difficult, owing to the continuous, high-energy Bremsstrahlung spectrum emitted by 90Y. This study aimed to evaluate the utility of a commercially available software package (HybridRecon, Hermes Medical Solutions AB) which incorporates full Monte Carlo collimator modelling. Analysis of image quality was performed on both phantom and clinical images in order to ultimately provide a recommendation of an optimum reconstruction for post-therapy 90Y microsphere SPECT/CT imaging. A 3D-printed anthropomorphic liver phantom was filled with 90Y with a sphere-to-background ratio of 4:1 and imaged on a GE Discovery 670 SPECT/CT camera. Datasets were reconstructed using ordered-subsets expectation maximization (OSEM) 1-7 iterations in order to identify the optimal OSEM reconstruction (5 iterations, 15 subsets). Quantitative analysis was subsequently carried out on phantom datasets obtained using four reconstruction algorithms: the default OSEM protocol (2 iterations, 10 subsets) and the optimised OSEM protocol, both with and without full Monte Carlo collimator modelling. The quantitative metrics contrast recovery (CR) and background variability (BV) were calculated. The four algorithms were then used to retrospectively reconstruct 10 selective internal radiation therapy (SIRT) patient datasets which were subsequently blind scored for image quality by a consultant radiologist. RESULTS: The optimised OSEM reconstruction (5 iterations, 15 subsets with full MC collimator modelling) increased the CR by 42% (p < 0.001) compared to the default OSEM protocol (2 iterations, 10 subsets). The use of full Monte Carlo collimator modelling was shown to further improve CR by 14% (30 mm sphere, CR = 90%, p < 0.05). The consultant radiologist had a significant preference for the optimised OSEM over the default OSEM protocol (p < 0.001), with the optimised OSEM being the favoured reconstruction in every one of the 10 clinical cases presented. CONCLUSIONS: OSEM (5 iterations, 15 subsets) with full Monte Carlo collimator modelling is quantitatively the optimal image reconstruction for post-SIRT 90Y Bremsstrahlung SPECT/CT imaging. The use of full Monte Carlo collimator modelling for correction of image-degrading effects significantly increases contrast recovery without degrading clinical image quality.

Ejection fraction in myocardial perfusion imaging assessed with a dynamic phantom: comparison between IQ-SPECT and LEHR.

BACKGROUND: Developments in single photon emission tomography instrumentation and reconstruction methods present a potential for decreasing acquisition times. One of such recent options for myocardial perfusion imaging (MPI) is IQ-SPECT. This study was motivated by the inconsistency in the reported ejection fraction (EF) and left ventricular (LV) volume results between IQ-SPECT and more conventional low-energy high-resolution (LEHR) collimation protocols. IQ-SPECT and LEHR quantitative results were compared while the equivalent number of iterations (EI) was varied. The end-diastolic (EDV) and end-systolic volumes (ESV) and the derived EF values were investigated. A dynamic heart phantom was used to produce repeatable ESVs, EDVs and EFs. Phantom performance was verified by comparing the set EF values to those measured from a gated multi-slice X-ray computed tomography (CT) scan (EFTrue). The phantom with an EF setting of 45, 55, 65 and 70% was imaged with both IQ-SPECT and LEHR protocols. The data were reconstructed with different EI, and two commonly used clinical myocardium delineation software were used to evaluate the LV volumes. RESULTS: The CT verification showed that the phantom EF settings were repeatable and accurate with the EFTrue being within 1% point from the manufacture's nominal value. Depending on EI both MPI protocols can be made to produce correct EF estimates, but IQ-SPECT protocol produced on average 41 and 42% smaller EDV and ESV when compared to the phantom's volumes, while LEHR protocol underestimated volumes by 24 and 21%, respectively. The volume results were largely similar between the delineation methods used. CONCLUSIONS: The reconstruction parameters can greatly affect the volume estimates obtained from perfusion studies. IQ-SPECT produces systematically smaller LV volumes than the conventional LEHR MPI protocol. The volume estimates are also software dependent.

Dosimetry software Hermes Internal Radiation Dosimetry: from quantitative image reconstruction to voxel-level absorbed dose distribution.

OBJECTIVE: The aim of this work is to validate a software package called Hermes Internal Radiation Dosimetry (HIRD) for internal dose assessment tailored for clinical practice. The software includes all the necessary steps to perform voxel-level absorbed dose calculations including quantitative reconstruction, image coregistration and volume of interest tools. METHODS: The basics of voxel-level dosimetry methods and implementations to HIRD software are reviewed. Then, HIRD is validated using simulated SPECT/CT data and data from Lu-DOTATATE-treated patients by comparing absorbed kidney doses with OLINDA/EXM-based dosimetry. In addition, electron and photon dose components are studied separately in an example patient case. RESULTS: The simulation study showed that HIRD can reproduce time-activity curves accurately and produce absorbed doses with less than 10% error for the kidneys, liver and spleen. From the patient data, the absorbed kidney doses calculated using HIRD and using OLINDA/EXM were highly correlated (Pearson's correlation coefficient, r=0.98). From Bland-Altman plot analysis, an average absorbed dose difference of -2% was found between the methods. In addition, we found that in Lu-DOTATATE-treated patients, photons can contribute over 10% of the kidney's total dose and is partly because of cross-irradiation from high-uptake lesions close to the kidneys. CONCLUSION: HIRD is a straightforward voxel-level internal dosimetry software. Its clinical utility was verified with simulated and clinical Lu-DOTATATE-treated patient data. Patient studies also showed that photon contribution towards the total dose can be relatively high and voxel-level dose calculations can be valuable in cases where the target organ is in close proximity to high-uptake organs.

Multicellular dosimetric chain for molecular radiotherapy exemplified with dose simulations on 3D cell spheroids.

PURPOSE: Absorbed radiation dose-response relationships are not clear in molecular radiotherapy (MRT). Here, we propose a voxel-based dose calculation system for multicellular dosimetry in MRT. We applied confocal microscope images of a spherical cell aggregate i.e. a spheroid, to examine the computation of dose distribution within a tissue from the distribution of radiopharmaceuticals. METHODS: A confocal microscope Z-stack of a human hepatocellular carcinoma HepG2 spheroid was segmented using a support-vector machine algorithm and a watershed function. Heterogeneity in activity uptake was simulated by selecting a varying amount of the cell nuclei to contain 111In, 125I, or 177Lu. Absorbed dose simulations were carried out using vxlPen, a software application based on the Monte Carlo code PENELOPE. RESULTS: We developed a schema for radiopharmaceutical dosimetry. The schema utilizes a partially supervised segmentation method for cell-level image data together with a novel main program for voxel-based radiation dose simulations. We observed that for 177Lu, radiation cross-fire enabled full dose coverage even if the radiopharmaceutical had accumulated to only 60% of the spheroid cells. This effect was not found with 111In and 125I. Using these Auger/internal conversion electron emitters seemed to guarantee that only the cells with a high enough activity uptake will accumulate a lethal amount of dose, while neighboring cells are spared. CONCLUSIONS: We computed absorbed radiation dose distributions in a 3D-cultured cell spheroid with a novel multicellular dosimetric chain. Combined with pharmacological studies in different tissue models, our cell-level dosimetric calculation method can clarify dose-response relationships for radiopharmaceuticals used in MRT.