• 90Y dosimetry
• PET/computed tomography (PET/CT)
• Positron emission tomography (PET)/magnetic resonance (MR)
• hepatic malignancy
• radioembolization

• Humans
• Positron Emission Tomography Computed Tomography
• Yttrium Radioisotopes/therapeutic use
• Positron-Emission Tomography
• Tomography, Emission-Computed, Single-Photon
• Liver Neoplasms/diagnostic imaging
• Liver Neoplasms/radiotherapy

• Narodowe Centrum Nauki

• Bremsstrahlung
• Characteristic X-rays
• Monte Carlo
• Nanoparticles
• Transarterial radioembolization

• Brachytherapy
• Metastatic liver cancer
• Microspheres
• Transarterial radioembolization
• Yttrium-90

• Brachytherapy/methods
• Carcinoma, Hepatocellular/therapy
• Embolization, Therapeutic/methods
• Humans
• Liver Neoplasms/radiotherapy
• Liver Neoplasms/secondary
• Microspheres
• United States
• Yttrium Radioisotopes/therapeutic use

• R50 CA275877 NCI NIH HHS

• Dosimetry
• Lung shunt fraction
• Monte Carlo
• Scatter correction

Selective internal radiation therapy with Yttrium-90 microspheres is an effective therapy for liver cancer and liver metastases. Yttrium-90 is mainly a high-energy beta particle emitter. These beta particles emit Bremsstrahlung radiation during their interaction with tissue making post-therapy imaging of the radioactivity distribution feasible. Nevertheless, image quality and quantification is difficult due to the continuous energy spectrum which makes resolution modelling, attenuation and scatter estimation challenging and therefore the dosimetry quantification is inaccurate. As a consequence a reconstruction algorithm able to improve resolution could be beneficial.

In this study, the hybrid kernelised expectation maximisation (HKEM) is used to improve resolution and contrast and reduce noise, in addition a modified HKEM called frozen HKEM (FHKEM) is investigated to further reduce noise. The iterative part of the FHKEM kernel was frozen at the 72nd sub-iteration. When using ordered subsets algorithms the data is divided in smaller subsets and the smallest algorithm iterative step is called sub-iteration. A NEMA phantom with spherical inserts was used for the optimisation and validation of the algorithm, and data from 5 patients treated with Selective internal radiation therapy were used as proof of clinical relevance of the method.

The results suggest a maximum improvement of 56% for region of interest mean recovery coefficient at fixed coefficient of variation and better identification of the hot volumes in the NEMA phantom. Similar improvements were achieved with patient data, showing 47% mean value improvement over the gold standard used in hospitals.

Such quantitative improvements could facilitate improved dosimetry calculations with SPECT when treating patients with Selective internal radiation therapy, as well as provide a more visible position of the cancerous lesions in the liver.

• Bremsstrahlung imaging
• Kernel method
• SPECT-CT
• Synergistic image reconstruction
• Tomographic image reconstruction

• Glass microsphere
• Monte Carlo
• Nanoparticles
• Planar imaging
• Transarterial radioembolization

Theranostics is an emerging paradigm that combines imaging and therapy in order to personalize patient treatment. In nuclear medicine, this is achieved by using radiopharmaceuticals that target identical molecular targets for both imaging (using emitted gamma rays) and radiopharmaceutical therapy (using emitted beta, alpha or Auger-electron particles) for the treatment of various diseases, such as cancer. If the therapeutic radiopharmaceutical cannot be imaged quantitatively, a “theranostic pair” imaging surrogate can be used to predict the absorbed radiation doses from the therapeutic radiopharmaceutical. However, theranostic dosimetry assumes that the pharmacokinetics and biodistributions of both radiopharmaceuticals in the pair are identical or very similar, an assumption that still requires further validation for many theranostic pairs. In this review, we consider both same-element and different-element theranostic pairs and attempt to determine if factors exist which may cause inaccurate dose extrapolations in theranostic dosimetry, either intrinsic (e.g. chemical differences) or extrinsic (e.g. injecting different amounts of each radiopharmaceutical) to the radiopharmaceuticals. We discuss the basis behind theranostic dosimetry and present common theranostic pairs and their therapeutic applications in oncology. We investigate general factors that could create alterations in the behavior of the radiopharmaceuticals or the quantitative accuracy of imaging them. Finally, we attempt to determine if there is evidence showing some specific pairs as suitable for theranostic dosimetry. We show that there are a variety of intrinsic and extrinsic factors which can significantly alter the behavior among pairs of radiopharmaceuticals, even if they belong to the same chemical element. More research is needed to determine the impact of these factors on theranostic dosimetry estimates and on patient outcomes, and how to correctly account for them.

• dosimetry
• personalized medicine
• radiopharmaceutical therapy
• radiopharmaceuticals
• theranostics

• 90Y PET
• 90Y microspheres
• 99mTc-MAA
• Liver dosimetry
• Lung shunt
• Prospective/retrospective dosimetry
• Radioembolization dosimetry
• Tumour dosimetry

• PET
• SPECT
• bremsstrahlung
• imaging
• interventional radiology
• radioembolization
• yttrium-90

• Monte-Carlo simulation
• SPECT
• pinhole
• system matrix
• ultra-high-resolution

Transarterial radioembolization (TARE) effectively treats unresectable primary and metastatic liver tumors through intra‐arterial injection of Yttrium‐90 (⁹⁰Y) beta particle emitting microspheres which implant around the tumor. Current dosimetry models are highly simplistic and there is a large need for an image‐based dosimetry post‐TARE, which would improve treatment safety and efficacy. Current post‐TARE imaging is ⁹⁰Y bremsstrahlung SPECT/CT and we study the use of these images for dosimetry. Retrospective image review of ten patients having a Philips Healthcare^TM SPECT/CT following TARE SIR‐Spheres® implantation. Emission series with attenuation correction were resampled to 3 mm resolution and used to create image‐based dose distributions. Dose distributions and analysis were performed in MIM Software SurePlan^TM utilizing SurePlan^TM Local Deposition Method (LDM) and a dose convolution method (WFBH). We sought to implement a patient‐specific background subtraction prior to dose calculation to make these noisy bremsstrahlung SPECT images suitable for post‐TARE dosimetry. On average the percentage of mean background counts to maximum count in the image across all patients was 9.4 ± 4.9% (maximum = 7.6%, minimum = 2.3%). Absolute dose increased and profile line width decreased as background subtraction value increased. The average value of the LDM and WFBH dose methods was statistically the same. As background subtraction value increased, the DVH curves become unrealistic and distorted. Background subtraction on bremsstrahlung SPECT image has a large effect on post‐TARE dosimetry. The background contour defined provides a systematic estimate to the activity background that accounts for the scanner and patient conditions at the time of the image study and is easily implemented using commercially available software. Using the mean count in the background contour as a subtraction across the entire image gave the most realistic dose distributions. This methodology is independent of microsphere and software manufacturer allowing for use with any available products or tools.

• Radioembolization
• Y90 Bremsstrahlung SPECT/CT
• dose distribution
• image-based dosimetry

• deep learning
• model observer
• task-based image quality assessment

• R01 CA240706 NCI NIH HHS
• R01 EB022075 NIBIB NIH HHS

• diagnostic performance
• liver cancer
• nuclear imaging
• theranostic radionuclides
• transarterial radioembolization

• Bremsstrahlung SPECT
• Dosimetry
• Radioembolization
• SIRT
• Yttrium-90
• Yttrium-90 PET

Gallium-67 (Ga-67) imaging is affected by collimator penetration and scatter components owing to the high-energy (HE) gamma-ray emissions. The characterization of penetration and scatter distribution is essential for the optimization of low-energy high-resolution (LEHR), medium energy (ME), and HE collimators and for the development of an effective correction technique. We compared the image quality that can be achieved by 3 collimators for different energy windows using the SIMIND Monte Carlo code.

Simulation experiments were conducted for LEHR, ME, and HE collimators for Ga-67 point source placed at 12-cm distance from the detector surface using the Monte Carlo SIMIND simulation code. Their spectra point spread functions as well as the original, penetration, scattering, and X-rays curves were drawn and analyzed. The parameters full-width at half maximum and full-width at tenth maximum were also investigated.

The original, penetration, and scatter curves within 10% for LEHR were 34.46%, 33.52%, 17.29%, and 14.72%, respectively. Similarly, the original, penetration, scatter, and X-rays within 10% for ME and HE were 83.06%, 10.25%, 6.69%, and 0% and 81.44%, 11.51%, 7.05%, and 0%, respectively. The trade-off between spatial resolution and sensitivity was achieved by using the ME collimator at 185 photopeak of Ga-67.

The Monte Carlo simulation outcomes can be applied for optimal collimator designing and for the development of new correction method in Ga-67 imaging.

• Ga-67 imaging
• penetration
• primary photons (original)
• scatter
• SIMIND
• sensitivity

• %FOV
• Bremsstrahlung imaging
• SPECT
• Signal-to-Background ratio
• Yttrium-90

• y-90
• spect
• joint spectral reconstruction
• bremsstrahlung
• energy-window subset

• Algorithms
• Image Processing, Computer-Assisted
• Likelihood Functions
• Monte Carlo Method
• Phantoms, Imaging
• Tomography, Emission-Computed, Single-Photon
• Yttrium Radioisotopes/therapeutic use

• R01 EB022075 NIBIB NIH HHS

Prior to ⁹⁰Y hepatic radioembolization, a dosage of ^99mTc‐macroaggregated albumin (^99mTc‐MAA) is administered to simulate the distribution of the ⁹⁰Y‐loaded microspheres. This pretreatment procedure enables lung shunt estimation, detection of potential extrahepatic depositions, and estimation of the intrahepatic dose distribution. However, the predictive accuracy of the MAA particle distribution is often limited. Ideally, ⁹⁰Y microspheres would also be used for the pretreatment procedure. Based on previous research, the pretreatment activity should be limited to the estimated safety threshold of 100 MBq, making imaging challenging. The purpose of this study was to evaluate the quality of intra‐ and extrahepatic imaging of ⁹⁰Y‐based pretreatment positron emission tomography/computed tomography (PET/CT) and quantitative single photon emission computed tomography (SPECT)/CT scans, by means of phantom experiments and a patient study.

An anthropomorphic phantom with three extrahepatic depositions was filled with ⁹⁰Y chloride to simulate a lung shunt fraction (LSF) of 5.3% and a tumor to nontumor ratio (T/N) of 7.9. PET /CT (Siemens Biograph mCT) and Bremsstrahlung SPECT/CT (Siemens Symbia T16) images were acquired at activities ranging from 1999 MBq down to 24 MBq, representing post‐ and pretreatment activities. PET/CT images were reconstructed with the clinical protocol and SPECT/CT images were reconstructed with a quantitative Monte Carlo‐based reconstruction protocol. Estimated LSF, T/N, contrast to noise ratio of all extrahepatic depositions, and liver parenchymal and tumor dose were compared with the phantom ground truth. A clinically reconstructed SPECT/CT of 150 MBq ^99mTc represented the current clinical standard. In addition, a ⁹⁰Y pretreatment scan was simulated for a patient by acquiring posttreatment PET/CT and SPECT/CT data with shortened acquisition times.

At an activity of 100 MBq ⁹⁰Y, PET/CT overestimated LSF [+10 percentage point (pp)], underestimated liver parenchymal dose (−3 Gy/GBq), and could not detect the extrahepatic depositions. SPECT/CT more accurately estimated LSF (−0.7 pp), parenchymal dose (−0.3 Gy/GBq) and could detect all three extrahepatic depositions. ^99mTc SPECT/CT showed similar accuracy as ⁹⁰Y SPECT/CT (LSF: +0.2 pp, parenchymal dose: +0.4 Gy/GBq, all extrahepatic depositions visible), although the noise level in the liver compartment was considerably lower for ^99mTc SPECT/CT compared to ⁹⁰Y SPECT/CT. The patient’s SPECT/CT simulating a pretreatment ⁹⁰Y procedure accurately represented the posttreatment ⁹⁰Y microsphere distribution.

Quantitative SPECT/CT of 100 MBq ⁹⁰Y could accurately estimate LSF, T/N, parenchymal and tumor dose, and visualize extrahepatic depositions.

• PET/CT
• SPECT/CT
• dosimetry
• radioembolization
• yttrium-90

• DMSA
• SPECT
• administered activity guidelines
• dose reduction/optimization
• pediatric imaging
• task-based image quality

The choice of the radionuclide has a key role in nuclear medicine which appearing the lowest scatter fraction. In addition, the presence of penetrated and scattered photons from collimator in single-photon emission computed tomography images degrades resolution and contrast. Thus, image quality depends on sensitivity and resolution of the collimator–detector system. The goal of this study was to compare the image quality that can be achieved by three radionuclides: technetium-99 m (Tc-99 m), iodine-123 (I-123), and samarium-153 (Sm-153).

Tc-99 m and Sm-153 were imaged with low-energy high resolution (LEHR) collimator, while I-123 was imaged with medium-energy (ME) collimator. We modeled the Siemens Symbia Medical system using Monte Carlo simulation code SIMIND. The imaging characteristics of each radionuclide were investigated by simulated data: point spread function, sensitivity (Cps/MBq) and geometric, penetration and scattering distribution.

Tc-99 m and Sm-153 give best and results with LEHR collimator for spatial resolution (full width at half maximum [FWHM] = 3.19 mm; full width at tenth maximum [FWTM] = 6.73 mm) and (FWHM = 3.22 mm; FWTM = 7.39 mm), respectively. Whereas, I-123 provided with ME collimator a lower resolution (FWHM = 4.89 mm; FWTM = 9.89 mm). The sensitivity recorded by Tc-99 m, Sm-153, and I-153 were (31.21 Cps/MBq), (10.16 Cps/MBq), and (51.22 Cps/MBq), respectively.

Tc-99 m and Sm-153 give the best and generally similar imaging properties with LEHR. For I-123, the ME collimator helps lowering the influence of high-energy gamma rays.

• Geometric
• SIMIND
• imaging
• penetration
• resolution
• scattering
• sensitivity

• 90Y
• 99mTc
• SPECT/CT
• dosimetry
• radiomicrosphere therapy

• Embolization, Therapeutic
• Humans
• Liver Neoplasms/radiotherapy
• Microspheres
• Phantoms, Imaging
• Prognosis
• Radiopharmaceuticals
• Radiotherapy Dosage
• Radiotherapy Planning, Computer-Assisted/methods
• Radiotherapy, Intensity-Modulated/methods
• Retrospective Studies
• Technetium Tc 99m Aggregated Albumin/therapeutic use
• Tomography, Emission-Computed, Single-Photon/methods
• Tomography, X-Ray Computed/methods
• Yttrium Radioisotopes/therapeutic use

• CNS-1532061 National Science Foundation

• Bremsstrahlung
• CNR
• Jaszczak phantom
• SIMIND
• yttrium-90 single-photon emission computed tomography imaging

Rhenium-188-labelled-Lipiodol radioembolization is a safe and cost-effective treatment for primary liver cancer. In order to determine correlations between treatment doses and patient response to therapy, accurate patient-specific dosimetry is required. Up to date, the reported dosimetry of ¹⁸⁸Re-Lipiodol has been based on whole-body (WB) planar imaging only, which has limited quantitative accuracy. The aim of the present study is to determine the in vivo pharmacokinetics, bio-distribution, and organ-level dosimetry of ¹⁸⁸Re-AHDD-Lipiodol radioembolization using a combination of post-treatment planar and quantitative SPECT/CT images. Furthermore, based on the analysis of the pharmacokinetic data, a practical and relatively simple imaging and dosimetry method that could be implemented in clinics for ¹⁸⁸Re-AHDD-Lipiodol radioembolization is proposed.

Thirteen patients with histologically proven hepatocellular carcinoma underwent ¹⁸⁸Re-AHDD-Lipiodol radioembolization. A series of 2–3 WB planar images and one SPECT/CT scan were acquired over 48 h after the treatment. The time-integrated activity coefficients (TIACs, also known as residence-times) and absorbed doses of tumors and organs at risk (OARs) were determined using a hybrid WB/SPECT imaging method.

Whole-body imaging showed that ¹⁸⁸Re-AHDD-Lipiodol accumulated mostly in the tumor and liver tissue but a non-negligible amount of the pharmaceutical was also observed in the stomach, lungs, salivary glands, spleen, kidneys, and urinary bladder. On average, the measured effective half-life of ¹⁸⁸Re-AHDD-Lipiodol was 12.5 ± 1.9 h in tumor. The effective half-life in the liver and lungs (the two organs at risk) was 12.6 ± 1.7 h and 12.0 ± 1.9 h, respectively. The presence of ¹⁸⁸Re in other organs was probably due to the chemical separation and subsequent release of the free radionuclide from Lipiodol.

The average doses per injected activity in the tumor, liver, and lungs were 23.5 ± 40.8 mGy/MBq, 2.12 ± 1.78 mGy/MBq, and 0.11 ± 0.05 mGy/MBq, respectively. The proposed imaging and dosimetry method, consisting of a single SPECT/CT for activity determination followed by ¹⁸⁸Re-AHDD-Lipiodol clearance with the liver effective half-life of 12.6 h, resulted in TIACs estimates (and hence, doses) mostly within ± 20% from the reference TIACs (estimated using three WB images and one SPECT/CT).

The large inter-patient variability of the absorbed doses in tumors and normal tissue in ¹⁸⁸Re-HDD-Lipiodol radioembolization patients emphasizes the importance of patient-specific dosimetry calculations based on quantitative post-treatment SPECT/CT imaging.

The online version of this article (10.1186/s40658-018-0227-6) contains supplementary material, which is available to authorized users.

• AHDD-Lipiodol
• Dosimetry
• Hepatocellular carcinoma
• Quantitative SPECT
• Radioembolization
• Rhenium-188

• Dose-effect relationship
• Dosimetry
• Personalized medicine
• Radiobiological model
• Radioembolization
• Theranostics

• Siemens USA

A major toxicity concern in radioembolization therapy of hepatic malignancies is radiation-induced pneumonitis and sclerosis due to hepatopulmonary shunting of ⁹⁰Y microspheres. Currently, ^99mTc macroaggregated albumin (^99mTc-MAA) imaging is used to estimate the lung shunt fraction (LSF) prior to treatment. The aim of this study was to evaluate the accuracy/precision of LSF estimated from ^99mTc planar and SPECT/CT phantom imaging, and within this context, to compare the corresponding LSF and lung-absorbed dose values from ^99mTc-MAA patient studies. Additionally, LSFs from pre- and post-therapy imaging were compared.

A liver/lung torso phantom filled with ^99mTc to achieve three lung shunt values was scanned by planar and SPECT/CT imaging with repeat acquisitions to assess accuracy and precision. To facilitate processing of patient data, a workflow that relies on SPECT and CT-based auto-contouring to define liver and lung volumes for the LSF calculation was implemented. Planar imaging-based LSF estimates for 40 patients, obtained from their medical records, were retrospectively compared with SPECT/CT imaging-based calculations with attenuation and scatter correction. Additionally, in a subset of 20 patients, the pre-therapy estimates were compared with ⁹⁰Y PET/CT-based measurements.

In the phantom study, improved accuracy in LSF estimation was achieved using SPECT/CT with attenuation and scatter correction (within 13% of the true value) compared with planar imaging (up to 44% overestimation). The results in patients showed a similar trend with planar imaging significantly overestimating LSF compared to SPECT/CT. There was no correlation between lung shunt estimates and the delay between ^99mTc-MAA administration and scanning, but off-target extra hepatic uptake tended to be more likely in patients with a longer delay. The mean lung absorbed dose predictions for the 28 patients who underwent therapy was 9.3 Gy (range 1.3–29.4) for planar imaging and 3.2 Gy (range 0.4–13.4) for SPECT/CT. For the patients with post-therapy imaging, the mean LSF from ⁹⁰Y PET/CT was 1.0%, (range 0.3–2.8). This value was not significantly different from the mean LSF estimate from ^99mTc-MAA SPECT/CT (mean 1.0%, range 0.4–1.6; p = 0.968), but was significantly lower than the mean LSF estimate based on planar imaging (mean 4.1%, range 1.2–15.0; p = 0.0002).

The improved accuracy demonstrated by the phantom study, agreement with ⁹⁰Y PET/CT in patient studies, and the practicality of using auto-contouring for liver/lung definition suggests that ^99mTc-MAA SPECT/CT with scatter and attenuation corrections should be used for lung shunt estimation prior to radioembolization.

• 90Y PET/CT
• 99mTc-MAA SPECT/CT
• Lung shunt
• Transarterial radioembolization (TARE)

• Humans
• Image Processing, Computer-Assisted/methods
• Monte Carlo Method
• Phantoms, Imaging
• Radiopharmaceuticals
• Single Photon Emission Computed Tomography Computed Tomography/methods
• Yttrium Radioisotopes

• R01 EB022075 NIBIB NIH HHS

• Arterially directed therapies
• Colorectal cancer liver metastases
• Hepatic malignancy
• Myelosuppression
• Radioembolization
• SIR-spheres
• SIRT
• Selective internal radiation therapy
• Yttrium-90

Radioembolization is an alternative palliative treatment for hepatocellular carcinoma. Here, we examine the uptake differences between tumor tissue phenotypes and present a cross-section of the absorbed dose throughout a liver tissue specimen.

A patient with hepatocellular carcinoma was treated with ⁹⁰Y radioembolization followed by liver tissue resection. Gamma camera images and autoradiographs were collected and biopsy tissue samples were analyzed using a gamma well counter and light microscopy.

An analysis of 25 punched biopsy tissue samples identified 4 tissue regions: Normal tissue, viable tumor tissue with and without infarcted areas, and tumor areas with postnecrotic scar tissue. Autoradiography and biopsy tissue sample measurements showed large dose differences between viable and postnecrotic tumor tissue (159 Gy vs 23 Gy).

Radioembolization of 90 yttrium with resin microspheres produces heterogeneous-absorbed dose distributions in the treatment of unifocal hepatic malignancies that could not be accurately determined with current gamma camera imaging techniques.

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.

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.

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.

• Image reconstruction
• Monte Carlo scatter correction
• Quantitative SPECT
• Yttrium-90 Bremsstrahlung

• SIRT
• SPECT
• dosimetry
• quantitation
• radioembolization