1. |
- Bauer, Florian, 1975-
(author)
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Detector Considerations for Time-of-Flight in Positron Emission Tomography
- 2009
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Doctoral thesis (other academic/artistic)abstract
- Positron-Emission-Tomography (PET) is a modern imaging technique in nuclear medicine providing quantitative 3D distribution of a radioactive tracer substance in the human body. The gamma-detector is the first link in the chain of components that constitutes a PET. It converts incoming radiation into optical light pulses, which are detected by photo multiplier tubes. Here the light is converted into electric pulses, to be further processed by the acquisition electronics. Improving detector sensitivity and resolution is of great value in research and in clinical practice. The focus of this work is to improve the detector to give it time-of-flight (TOF) capabilities, in order to further improve sensitivity, which in turn leads to increased image quality, faster scan time and/or reduced dose exposure for the patient. Image quality has improved over the years, but losses in image quality have been reported for heavy patients, due to increased attenuation, and more dispersed counts over a larger volume. Instrumentation limits are still significant in heavy patient images, but the incorporation of TOF information promises to alleviate some of the limitations. In order to improve the timing resolution of the detector fast photo-multipliers and a novel scheme to extract the event timing trigger from a detector by using the summed dynode signal were investigated. When designing new PET detectors, it is important to have detailed understanding and control of the light sharing mechanisms in the crystal arrays. Therefore it was necessary to perform optical simulations and single crystal light output measurements to derive a model for an LSO block detector. Another way to improve the image quality is to use the depth-of-interaction (DOI) of the gamma ray within the detector. It is shown that a multi-layer phoswich detector comprised of LSO with different decay times and TOF capability, combines the benefits of TOF and DOI in one detector, maximizing the effective sensitivity gain.
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2. |
- Dahlbom, Magnus, et al.
(author)
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Effects of high photon fluence rate from therapeutic radionuclides on preclinical and clinical PET systems
- 2016
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In: 2014 IEEE Nuclear Science Symposium and Medical Imaging Conference, NSS/MIC 2014. - 9781479960972
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Conference paper (peer-reviewed)abstract
- Tumor response in radionuclide therapy can be monitored with PET/CT and/or PET/MR. A high background photon fluence from a therapy radionuclide may influence both image quality and quantification, when imaging is performed intra-therapeutically, i.e. with high activity of the therapeutic radionuclide present. Here, count losses and image distortion have been investigated for preclinical and clinical PET systems with different detector designs. The effect on the spatial resolution was studied with a point source of 22Na in a background of 99mTc, where 99mTc emulated the photon emission from a therapeutic radionuclide. An in-house made mouse phantom with silicon tubes filled with 99mTc with a centrally placed 22Na point source was used. For the clinical systems, a 70 cm long NEMA PET Scatter Phantom was used, with a 22Na point source placed at the center whereas the off-center silicon tube was filled with 99mTc. In addition, image quality was also evaluated in the presence of different levels of 99mTc with a 18F-filled NEMA image quality phantom on the preclinical systems and a 18F-filled Jaszczak phantom on the clinical system. Preclinical PET systems with different detector geometries showed that the addition of 99mTc affected the count rate capability considerably, especially those with a low number of read-out channels. The coincidence rate for was significantly reduced when high activities of 99mTc were present. The clinical PET system also showed an effect of reduced coincidence rate with increased photon fluence rate. At high 99mTc activities, the spatial resolution was degraded for both the preclinical and the clinical systems. The quantitative capability of PET systems used intra-therapeutically is significantly affected by the additional high photon fluence rate. The dead-time correction implemented on some of the investigated PET systems, was able to accurately compensate for the coincidence count losses. The reduced spatial resolution at high photon fluence rate, however, remains a potentially limiting factor.
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3. |
- Dahlbom, Sixten, et al.
(author)
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Fire Test Performance of Eleven PFAS-Free Class B Firefighting Foams Varying Fuels, Admixture, Water Types and Foam Generation Techniques
- 2022
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In: Fire technology. - : Springer Science and Business Media LLC. - 0015-2684 .- 1572-8099. ; 58:3, s. 1639-1665
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Journal article (peer-reviewed)abstract
- The firefighting performance of eleven PFAS-free firefighting foams was evaluated using different fuels (Jet A1, commercial heptane and diesel) and types of water (freshwater and synthetic sea water). Moreover, different firefighting foam generation techniques and application methods were evaluated. The firefighting foams were generated as aspirated foams or as compressed air foams (CAFs). The results for CAF showed a higher performance, with respect to extinction time and burn-back resistance, compared to the foam generated using a UNI 86 nozzle. The CAF was not optimised, indicating a further potential of this foam generation technique. The results indicate that the time to fire knockdown decreases with decreasing foam viscosity. The heat flux was shown to be small, although the entire fuel surface was involved in the fire. The tests showed a dependence on fuel type; different products performed differently depending on the fuel. Tests using sea water showed that addition of salt to the foam solution generally prolonged the extinction time, although for one of the firefighting foams a shorter extinction time was observed. Out of the eleven evaluated PFAS-free products there was no product that outperformed the rest. None of the products in the study met the fire test performance requirements in all the referenced standards. Instead, the products seem to have different niches where they perform best e.g., with different types of fuel or water.
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4. |
- Häggström, Ida, 1982-
(author)
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Quantitative methods for tumor imaging with dynamic PET
- 2014
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Doctoral thesis (other academic/artistic)abstract
- There is always a need and drive to improve modern cancer care. Dynamic positron emission tomography (PET) offers the advantage of in vivo functional imaging, combined with the ability to follow the physiological processes over time. In addition, by applying tracer kinetic modeling to the dynamic PET data, thus estimating pharmacokinetic parameters associated to e.g. glucose metabolism, cell proliferation etc., more information about the tissue's underlying biology and physiology can be determined. This supplementary information can potentially be a considerable aid when it comes to the segmentation, diagnosis, staging, treatment planning, early treatment response monitoring and follow-up of cancerous tumors.We have found it feasible to use kinetic parameters for semi-automatic tumor segmentation, and found parametric images to have higher contrast compared to static PET uptake images. There are however many possible sources of errors and uncertainties in kinetic parameters obtained through compartment modeling of dynamic PET data. The variation in the number of detected photons caused by the random nature of radioactive decay, is of course always a major source. Other sources may include: the choice of an appropriate model that is suitable for the radiotracer in question, camera detectors and electronics, image acquisition protocol, image reconstruction algorithm with corrections (attenuation, random and scattered coincidences, detector uniformity, decay) and so on. We have found the early frame sampling scheme in dynamic PET to affect the bias and uncertainty in calculated kinetic parameters, and that scatter corrections are necessary for most but not all parameter estimates. Furthermore, analytical image reconstruction algorithms seem more suited for compartment modeling applications compared to iterative algorithms.This thesis and included papers show potential applications and tools for quantitative pharmacokinetic parameters in oncology, and help understand errors and uncertainties associated with them. The aim is to contribute to the long-term goal of enabling the use of dynamic PET and pharmacokinetic parameters for improvements of today's cancer care.
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5. |
- Jonsson, Cathrine, 1969-
(author)
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Advances in quantitative emission tomography : development and analysis of methods for validation and correction
- 2000
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Doctoral thesis (other academic/artistic)abstract
- The nuclear medicine imaging techniques SPECT and PET are sensitive tools in mapping various physiological and biochemical processes in vivo. This work was devoted to investigations of methodological and physical properties of the SPECT technique as well as developing methods for validation and correction. Brain imaging was the major focus in this work, but the results are applicable to other examination areas. In the first part regional cerebral blood flow (rCBF) as measured by PET - the golden standard - and by SPECT was compared using a computerised brain atlas. Overall the differences were surprisingly small but revealed an apparent reduced grey-to-white matter ratio for SPECT, mainly due to the lack of scatter correction in SPECT, a lower spatial resolution and a non-linear extraction of the SPECT radiopharmaceutical. Furthermore, the reproducibility of resting state rCBF with SPECT was investigated, imperative information whenever scans are being repeated, as in activation studies, or when comparing an individual scan to a database of scans from healthy individuals. The results indicate that normalised flow data show high intra- and inter-individual reproducibility, expressed as standard deviations, ±1.3% and ±2.9%, respectively. The major error was addressed to the methodology, i.e. the scanning procedure and the atlas adaptation.At that stage of the study, using a clinical protocol, without scatter correction and proper attenuation correction there was no possibility to extract quantitative information from the SPECT images. Therefore, in the subsequent work, a phantom concept (the stack phantom) was designed aiming at experimental validation of the SPECT methodology, including effects of photon interactions. Extracting information where the primary (unscattered) photons are separated from the ones undergoing scattering or attenuation before detection, was, until now, only possible using Monte Carlo simulations. The basis of the novel phantom concept is to sample various 3D-activity distributions from a set of 2D samples. The 2D samples are ordinary paper sheets where the cross sectional radioactivity distribution is printed out using radioactive ink. Mounting the samples together with a certain equidistant axial spacing, using either tissue equivalent material or some low-density material, give possibilities to mimick the very same activity distribution clinically (with degrading photon interactions) as well as almost "pure" primary photon images. The phantom concept is very flexible, any activity distribution may be constructed, pathological patterns can easily be introduced and varied. Moreover, correction methods and software evaluation tools may be assessed and validated with the phantom. However, the phantom has not only applicability in research areas - recurrent quality assurance programs can as well make use of dedicated stack phantoms.In the last phase of this work a scatter correction algorithm was developed, making use of the stack phantom. The correction was developed using a multi-spectral acquisition system. This allowed for spectral acquisitions in each pixel in the projection images. After correcting for the scatter contribution in the upper half of the photo-peak using the shape of the scatter distribution from the Klein-Nishina cross section the resulting estimate of primary photons was mirrored (folded) over to estimate the primary photons in the lower half of the photo-peak. The scatter correction works in each spectrum and hence corrects for the scatter contribution locally. The correction method was validated both with Monte Carlo simulations and the stack-phantom, both indicating accurate results.
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6. |
- Mellhammar, Emma, et al.
(author)
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An attenuation method for reducing count rate losses in preclinical PET during intratherapeutic imaging
- 2017
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In: 2016 IEEE Nuclear Science Symposium, Medical Imaging Conference and Room-Temperature Semiconductor Detector Workshop, NSS/MIC/RTSD 2016. - 9781509016426 ; 2017-January
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Conference paper (peer-reviewed)abstract
- In pre-clinical imaging, tumor response to radionuclide therapy can be monitored with PET imaging. Radionuclides used for therapy such as 177Lu emit a significant amount of low energy photons. These photons may have an energy high enough to penetrate the imaged object and are the prone to be detected. Although these phtons are likely to be rejected electronically, they add dead-time to the system since they need to be processed by the electronics. This is a problem in high-sensitivity pre-clinical PET system with a low number of readout channels, such as the Genisys G8 investigated in this work. The low energy gammas may also affect image quality due to increased probability of pulse pile-up. The use of high-attenuating shields designed to absorb most of the low energy photons emitted from the therapeutic radionuclide were investigated. Cylindrical led shields were constructed with thicknesses between 1 and 3 mm. A 3mm thick cylindrical shield was also constructed out of Rose metal (50% Bi, 28% Pb, and 22% Sn). The diameter of the shield was wide enough to accommodate a NEMA IQ phantom and a mouse. The attenuation of the shields for annihilation radiation was measured with a 22Na point source placed at the center of the FOV. Measurements of the coincidence rate were performed with the lead shields in place. At a of thicknesses of 1 and 3mm, the coincidence rate was reduced by a factor or 0.70 and 0.40, respectively. To study the effect of the presence of a background of low energy gammas on the coincidence count rate and the efficacy of the lead shields, 177Lu was added to a 1 cm diameter hollow sphere. In the presence of 100 MBq of 177Lu, the coincidence count rate was reduced by a factor 0.20 due to the detector dead-time. Although the count rate was reduced by a factor of 0.40 with the 3mm shield around the source, the dead-time effects due to the 177Lu background were less than 7%. 18F imaging of a NEMA phantom and a tumor bearing mouse showed dramatic image distortions in the presence of the 177Lu background. When imaging of with the 3mm shield in place, the image distortions were eliminated and were comparable in to the images acquired without the background activity.
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7. |
- Mellhammar, Emma Matilda, et al.
(author)
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Count rate characteristics and image distortion in preclinical PET systems during intratherapeutic radiopharmaceutical therapy imaging
- 2016
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In: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 2159-662X. ; 57:12, s. 1964-1970
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Journal article (peer-reviewed)abstract
- Positron emission tomography (PET) may provide important information on the therapeutic response of radiopharmaceutical therapy (RPT) during therapy. The radiation emission from the RPT radionuclide may disturb the coincidence detection and impair the image resolution. In this study we tested the feasibility to perform intratherapeutic PET on three preclinical PET systems.METHODS: Using (22)Na point sources and phantoms filled with (18)F, and a phantom filled with either (99m)Tc or (177)Lu, the coincidence count rate and the spatial resolution when both a PET and a therapeutic radionuclide were present in the PET camera, were evaluated. (99m)Tc was used as a substitute for a generic therapeutic radioisotope, since it has a suitable half-life and is easy obtainable.RESULTS: High activities of (99m)Tc deteriorated the coincidence count rate from the (18)F-filled phantom with a (22)Na point source on all three systems evaluated. One of the systems could to a high degree correct the count rate with its dead time correction. The spatial resolution was degraded at high activities of (99m)Tc for all systems. On one of the systems (177)Lu increased the coincidence count rate and slightly affected the spatial resolution. The results for high activities of (177)Lu were similar to those for (99m)Tc.CONCLUSION: Intratherapeutic imaging might be a feasible method to study RPT treatment response. However, some sensitive preclinical PET systems, unable to handle high count rates, suffer count losses and may also introduce image artifacts.
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8. |
- Mellhammar, Emma, et al.
(author)
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Preserving Preclinical PET Quality During Intratherapeutic Imaging in Radionuclide Therapy with Rose Metal Shielding Reducing Photon Flux
- 2019
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In: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 2159-662X. ; 60:5, s. 710-715
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Journal article (peer-reviewed)abstract
- Performing PET imaging during ongoing radionuclide therapy can be a promising method to follow tumor response in vivo. However, the high therapeutic activity can interfere with the PET camera performance and degrade both image quality and quantitative capabilities. As a solution, low-energy photon emissions from the therapeutic radionuclide can be highly attenuated, still allowing sufficient detection of annihilation photons in coincidence. Methods: Hollow Rose metal cylinders with walls 2-4 mm thick were used to shield a 22Na point source and a uniform phantom filled with 18F as they were imaged on a preclinical PET camera with increasing activities of 177Lu. A mouse with a subcutaneous tumor was injected with 18F-FDG and imaged with an additional 120 MBq of 177Lu and repeated with shields surrounding the animal. Results: The addition of 177Lu to the volume imaged continuously degraded the image quality with increasing activity. The image quality was improved when shielding was introduced. The shields showed a high ability to produce stable and reproducible results for both spatial resolution and quantification of up to 120 MBq of 177Lu activity (maximum activity tested). Conclusion: Without shielding, the activity quantification will be inaccurate for time points at which therapeutic activities are high. The suggested method shows that the shields reduce the noise induced by the 177Lu and therefore enable longitudinal quantitative intratherapeutic imaging studies.
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9. |
- Mellhammar, Emma, et al.
(author)
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Small-scale dosimetry for alpha particle 241Am source cell irradiation and estimation of γ-H2AX foci distribution in prostate cancer cell line PC3
- 2022
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In: EJNMMI Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 9:1
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Journal article (peer-reviewed)abstract
- Background: The development of new targeted alpha therapies motivates improving alpha particle dosimetry. For alpha particles, microscopic targets must be considered to estimate dosimetric quantities that can predict the biological response. As double-strand breaks (DSB) on DNA are the main cause of cell death by ionizing radiation, cell nuclei are relevant volumes necessary to consider as targets. Since a large variance is expected of alpha particle hits in individual cell nuclei irradiated by an uncollimated alpha-emitting source, the damage induced should have a similar distribution. The induction of DSB can be measured by immunofluorescent γ-H2AX staining. The cell γ-H2AX foci distribution and alpha particle hits distribution should be comparable and thereby verify the necessity to consider the relevant dosimetric volumes. Methods: A Monte Carlo simulation model of an 241Am source alpha particle irradiation setup was combined with two versions of realistic cell nuclei phantoms. These were generated from DAPI-stained PC3 cells imaged with fluorescent microscopy, one consisting of elliptical cylinders and the other of segmented mesh volumes. PC3 cells were irradiated with the 241Am source for 4, 8 and 12 min, and after 30 min fixated and stained with immunofluorescent γ-H2AX marker. The detected radiation-induced foci (RIF) were compared to simulated RIF. Results: The mesh volume phantom detected a higher mean of alpha particle hits and energy imparted (MeV) per cell nuclei than the elliptical cylinder phantom, but the mean specific energy (Gy) was very similar. The mesh volume phantom detected a slightly larger variance between individual cells, stemming from the more extreme and less continuous distribution of cell nuclei sizes represented in this phantom. The simulated RIF distribution from both phantoms was in good agreement with the detected RIF, although the detected distribution had a zero-inflated shape not seen in the simulated distributions. An estimate of undetected foci was used to correct the detected RIF distribution and improved the agreement with the simulations. Conclusion: Two methods to generate cell nuclei phantoms for Monte Carlo dosimetry simulations were tested and generated similar results. The simulated and detected RIF distributions from alpha particle-irradiated PC3 cells were in good agreement, proposing the necessity to consider microscopic targets in alpha particle dosimetry.
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10. |
- Mellhammar, Emma, et al.
(author)
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Tumor Control Probability and Small-Scale Monte Carlo Dosimetry : Effects of Heterogenous Intratumoral Activity Distribution in Radiopharmaceutical Therapy
- 2023
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In: Journal of Nuclear Medicine. - 0161-5505. ; 64:10, s. 1-6
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Journal article (peer-reviewed)abstract
- In radiopharmaceutical therapy, intratumoral uptake of radioactivity usually leads to heterogeneous absorbed dose distribution. The likelihood of treatment success can be estimated with the tumor control probability (TCP), which requires accurate dosimetry, estimating the absorbed dose rate per unit activity to individual tumor cells. Methods: Xenograft cryosections of the prostate cancer cell line LNCaP treated with [177Lu]Lu-PSMA-617 were evaluated with digital autoradiography and stained with hematoxylin and eosin. The digital autoradiography images were used to define the source in a Monte Carlo simulation of the absorbed dose, and the stained sections were used to detect the position of cell nuclei to relate the intratumoral absorbed dose heterogeneity to the cell density. Simulations were performed for 225Ac, 177Lu, and 90Y. TCP was calculated to estimate the mean necessary injected activity for a high TCP. A hypothetical case of activity mainly taken up on the tumor borders was generated and used to simulate the absorbed dose. Results: The absorbed dose per decay to tumor cells was calculated from the staining and simulation results to avoid underestimating the tumor response from low absorbed doses in tumor regions with low cell density. The mean of necessary injected activity to reach a 90% TCP for 225Ac, 177Lu, and 90Y was found to be 18.3 kBq (range, 18–22 kBq), 24.3 MBq (range, 20–29 MBq), and 5.6 MBq (range, 5–6 MBq), respectively. Conclusion: To account for the heterogeneous absorbed dose generated from nonuniform intratumoral activity uptake, dosimetry models can estimate the mean necessary activity to reach a sufficient TCP for treatment response. This approach is necessary to accurately evaluate the efficacy of suggested radiopharmaceuticals for therapy.
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