The clinical utility of digital and long field-of-view positron emission/computed tomography for oncology

Aim: To evaluate the performance of a state-of-the-art digital (dPET/CT) and long field-of-view (LAFOV) positron emission/computer tomography (PET/CT) system and to quantify how this translates into improved image quality, lesion detection, diagnostic certainty, lower dose, faster examinations and improved dynamic range. In doing so, some of the first evidence for these novel systems is provided. Methods: This thesis presents five studies which evaluate state-of-the-art dPET/CT systems by means of a matched-pair comparison of a digital with an analogue system, their performance and influence on diagnostic certainty and interrater reliability, the feasibility of reduced applied radiopharmaceutical activities in digital systems, the clinical performance of a novel LAFOV PET/CT system and the feasibility of using these for late acquisition of images for the diagnosis of recurrent prostate cancer. Results: dPET/CT systems revealed higher detection rate compared to an analogue PET/CT system as well as improved interrater reliability and diagnostic certainty. dPET/CT systems allow for 75% reduction in applied radiopharmaceutical activity or scan time. LAFOV PET/CT furnish orders of magnitude increases in count density, the possibility to reduce the total examination time to 30s or reductions in applied activity as well as the ability to examine at much later time points once multiple half-lives have elapsed without detriment to image quality. Conclusion: Digital and LAFOV PET/CT systems exhibit improved performance when compared to analogue and short-axial field-of-view systems, with demonstrated improvement in clinically relevant outcomes such as improved detection rate and diagnostic certainty

Evaluation of image signal-to-noise ratio in time-of-flight PET

In PET imaging Noise Equivalent Counts (NEC) is a common image quality index, derived to be proportional to image SNR 2 and used as an index of general system performance. Many studies have shown that TOF information leads to reduced noise, faster image convergence, and improved SNR. However, the original NEC formula does not account for any contribution of timing resolution to the final image quality, and modified versions of the formula have been proposed to account for the reduction in noise variance and increased sensitivity due to TOF information. In this study, we aim to investigate the relationship between NEC and image SNR in uniform phantoms when OSEM and TOF OSEM image reconstruction is applied. Two cylindrical uniform phantoms, 20 and 35 cm in diameter, were acquired over a wide range of activity levels on a Philips Gemini TF PET scanner. Multiple realizations of the original scans were obtained through bootstrapping and reconstructed with OSEM and TOF OSEM algorithms to obtain mean and standard deviation images. The ratio of the mean value in a central ROI over both images was taken as a measure of image SNR. NEC was calculated from the original data using both the classical and a TOF-adapted formula. The results show that Trues have a better proportionality with image SNR 2 than NEC and TOF NEC in the considered range of activities. Timing resolution and Random fraction appear to have a limited influence on image SNR, but the usage of a matched TOF kernel in reconstruction is found to be necessary to maximize the gain

State of art and next challenges in instrumentation for quality control in hadrontherapy centres

In this document we aim at summarising the different points so far addressed and those that are still to be resolved in instrumentation for quality control in hadrontherapy centres. This includes on line in beam PET for dose deposition monitoring, beam hodoscope and prompt gamma monitoring

State of the art in total body PET

The idea of a very sensitive positron emission tomography (PET) system covering a large portion of the body of a patient already dates back to the early 1990s. In the period 2000–2010, only some prototypes with long axial field of view (FOV) have been built, which never resulted in systems used for clinical research. One of the reasons was the limitations in the available detector technology, which did not yet have sufficient energy resolution, timing resolution or countrate capabilities for fully exploiting the benefits of a long axial FOV design. PET was also not yet as widespread as it is today: the growth in oncology, which has become the major application of PET, appeared only after the introduction of PET-CT (early 2000).The detector technology used in most clinical PET systems today has a combination of good energy and timing resolution with higher countrate capabilities and has now been used since more than a decade to build time-of-flight (TOF) PET systems with fully 3D acquisitions. Based on this technology, one can construct total body PET systems and the remaining challenges (data handling, fast image reconstruction, detector cooling) are mostly related to engineering. The direct benefits of long axial FOV systems are mostly related to the higher sensitivity. For single organ imaging, the gain is close to the point source sensitivity which increases linearly with the axial length until it is limited by solid angle and attenuation of the body. The gains for single organ (compared to a fully 3D PET 20-cm axial FOV) are limited to a factor 3–4. But for long objects (like body scans), it increases quadratically with scanner length and factors of 10–40 × higher sensitivity are predicted for the long axial FOV scanner. This application of PET has seen a major increase (mostly in oncology) during the last 2 decades and is now the main type of study in a PET centre. As the technology is available and the full body concept also seems to match with existing applications, the old concept of a total body PET scanner is seeing a clear revival. Several research groups are working on this concept and after showing the potential via extensive simulations; construction of these systems has started about 2 years ago. In the first phase, two PET systems with long axial FOV suitable for large animal imaging were constructed to explore the potential in more experimental settings. Recently, the first completed total body PET systems for human use, a 70-cm-long system, called PennPET Explorer, and a 2-m-long system, called uExplorer, have become reality and first clinical studies have been shown. These results illustrate the large potential of this concept with regard to low-dose imaging, faster scanning, whole-body dynamic imaging and follow-up of tracers over longer periods. This large range of possible technical improvements seems to have the potential to change the current clinical routine and to expand the number of clinical applications of molecular imaging. The J-PET prototype is a prototype system with a long axial FOV built from axially arranged plastic scintillator strips.This paper gives an overview of the recent technical developments with regard to PET scanners with a long axial FOV covering at least the majority of the body (so called total body PET systems). After explaining the benefits and challenges of total body PET systems, the different total body PET system designs proposed for large animal and clinical imaging are described in detail. The axial length is one of the major factors determining the total cost of the system, but there are also other options in detector technology, design and processing for reducing the cost these systems. The limitations and advantages of different designs for research and clinical use are discussed taking into account potential applications and the increased cost of these systems

Transesterification of Poly(Ethylene Terephthalate) and Bisphenol-A-Polycarbonate

Blends of Poly(ethylene terephthalate) (PET) and bisphenol-A-polycarbonate (PC) have been made by solution and melt blending and these blends were subject to isothermal heating to induce a transesterification reaction. The raw materials and products of this reaction have been studied by a variety of different methods to ascertain the chemical, physical and mechanical properties they possess. The conclusions drawn are listed below. PET and PC are immiscible but are compatibilised by transesterification. Transesterification is a second order reversible process and is fast only when water is present, when absent the rate of transesterification is so slow that little or no reaction is observed in after 60 minutes at 300 c. When water is present in the blend significant chain scission and degradation takes place, this is not observed in the absence of water• The material obtained from melt blending has a molecular weight higher than that of commercial PET and it is possible to increase it further by standard solid state polymerization techniques. The PC concentration in PET is critical to the existence and extent of crystallisation. PET blends containing 10% PC are not significantly stronger or weaker than commercial PET and perform very similarly to the yield point. PET blends containing 10% PC are less ductile than commercial PET and will therefore fail sooner when they have yielded under tension. PET blends containing 10% PC do not injection mould as well as commercial PET under conventional procedures for PET, surface crazing and voiding is observe

Magnetic Resonance-Based Attenuation Correction and Scatter Correction in Neurological Positron Emission Tomography/Magnetic Resonance Imaging—Current Status With Emerging Applications

In this review, we will summarize the past and current state-of-the-art developments in attenuation and scatter correction approaches for hybrid positron emission tomography (PET) and magnetic resonance (MR) imaging. The current status of the methodological advances for producing accurate attenuation and scatter corrections on PET/MR systems are described, in addition to emerging clinical and research applications. Future prospects and potential applications that benefit from accurate data corrections to improve the quantitative accuracy and clinical applicability of PET/MR are also discussed. Novel clinical and research applications where improved attenuation and scatter correction methods are beneficial are highlighted

[¹⁸F]fluorination of biorelevant arylboronic acid pinacol ester scaffolds synthesized by convergence techniques

Aim: The development of small molecules through convergent multicomponent reactions (MCR) has been boosted during the last decade due to the ability to synthesize, virtually without any side-products, numerous small drug-like molecules with several degrees of structural diversity.(1) The association of positron emission tomography (PET) labeling techniques in line with the “one-pot” development of biologically active compounds has the potential to become relevant not only for the evaluation and characterization of those MCR products through molecular imaging, but also to increase the library of radiotracers available. Therefore, since the [18F]fluorination of arylboronic acid pinacol ester derivatives tolerates electron-poor and electro-rich arenes and various functional groups,(2) the main goal of this research work was to achieve the 18F-radiolabeling of several different molecules synthesized through MCR. Materials and Methods: [18F]Fluorination of boronic acid pinacol esters was first extensively optimized using a benzaldehyde derivative in relation to the ideal amount of Cu(II) catalyst and precursor to be used, as well as the reaction solvent. Radiochemical conversion (RCC) yields were assessed by TLC-SG. The optimized radiolabeling conditions were subsequently applied to several structurally different MCR scaffolds comprising biologically relevant pharmacophores (e.g. β-lactam, morpholine, tetrazole, oxazole) that were synthesized to specifically contain a boronic acid pinacol ester group. Results: Radiolabeling with fluorine-18 was achieved with volumes (800 μl) and activities (≤ 2 GBq) compatible with most radiochemistry techniques and modules. In summary, an increase in the quantities of precursor or Cu(II) catalyst lead to higher conversion yields. An optimal amount of precursor (0.06 mmol) and Cu(OTf)2(py)4 (0.04 mmol) was defined for further reactions, with DMA being a preferential solvent over DMF. RCC yields from 15% to 76%, depending on the scaffold, were reproducibly achieved. Interestingly, it was noticed that the structure of the scaffolds, beyond the arylboronic acid, exerts some influence in the final RCC, with electron-withdrawing groups in the para position apparently enhancing the radiolabeling yield. Conclusion: The developed method with high RCC and reproducibility has the potential to be applied in line with MCR and also has a possibility to be incorporated in a later stage of this convergent “one-pot” synthesis strategy. Further studies are currently ongoing to apply this radiolabeling concept to fluorine-containing approved drugs whose boronic acid pinacol ester precursors can be synthesized through MCR (e.g. atorvastatin)