Heather A. Williams

A comparison of PET imaging characteristics of various copper radioisotopes

PurposePET radiotracers which incorporate longer-lived radionuclides enable biological processes to be studied over many hours, at centres remote from a cyclotron. This paper examines the radioisotope characteristics, imaging performance, radiation dosimetry and production modes of the four copper radioisotopes, 60Cu, 61Cu, 62Cu and 64Cu, to assess their merits for different PET imaging applications. MethodsSpatial resolution, sensitivity, scatter fraction and noise-equivalent count rate (NEC) are predicted for 60Cu, 61Cu, 62Cu and 64Cu using a model incorporating radionuclide decay properties and scanner parameters for the GE Advance scanner. Dosimetry for 60Cu, 61Cu and 64Cu is performed using the MIRD model and published biodistribution data for copper(II) pyruvaldehyde bis(N4-methyl)thiosemicarbazone (Cu-PTSM). Results60Cu and 62Cu are characterised by shorter half-lives and higher sensitivity and NEC, making them more suitable for studying the faster kinetics of small molecules, such as Cu-PTSM. 61Cu and 64Cu have longer half-lives, enabling studies of the slower kinetics of cells and peptides and prolonged imaging to compensate for lower sensitivity, together with better spatial resolution, which partially compensates for loss of image contrast. 61Cu-PTSM and 64Cu-PTSM are associated with radiation doses similar to [18F]-fluorodeoxyglucose, whilst the doses for 60Cu-PTSM and 62Cu-PTSM are lower and more comparable with H215O. ConclusionThe physical and radiochemical characteristics of the four copper isotopes make each more suited to some imaging tasks than others. The results presented here assist in selecting the preferred radioisotope for a given imaging application, and illustrate a strategy which can be extended to the majority of novel PET tracers.

Impact of point spread function modelling and time of flight on FDG uptake measurements in lung lesions using alternative filtering strategies

BackgroundThe use of maximum standardised uptake value (SUVmax) is commonplace in oncology positron emission tomography (PET). Point spread function (PSF) modelling and time-of-flight (TOF) reconstructions have a significant impact on SUVmax, presenting a challenge for centres with defined protocols for lesion classification based on SUVmax thresholds. This has perhaps led to the slow adoption of these reconstructions. This work evaluated the impact of PSF and/or TOF reconstructions on SUVmax, SUVpeak and total lesion glycolysis (TLG) under two different schemes of post-filtering.MethodsPost-filters to match voxel variance or SUVmax were determined using a NEMA NU-2 phantom. Images from 68 consecutive lung cancer patients were reconstructed with the standard iterative algorithm along with TOF; PSF modelling - Siemens HD·PET (HD); and combined PSF modelling and TOF - Siemens ultraHD·PET (UHD) with the two post-filter sets. SUVmax, SUVpeak, TLG and signal-to-noise ratio of tumour relative to liver (SNR(T-L)) were measured in 74 lesions for each reconstruction. Relative differences in uptake measures were calculated, and the clinical impact of any changes was assessed using published guidelines and local practice.ResultsWhen matching voxel variance, SUVmax increased substantially (mean increase +32% and +49% for HD and UHD, respectively), potentially impacting outcome in the majority of patients. Increases in SUVpeak were less notable (mean increase +17% and +23% for HD and UHD, respectively). Increases with TOF alone were far less for both measures. Mean changes to TLG were <10% for all algorithms for either set of post-filters. SNR(T-L) were greater than ordered subset expectation maximisation (OSEM) in all reconstructions using both post-filtering sets.ConclusionsMatching image voxel variance with PSF and/or TOF reconstructions, particularly with PSF modelling and in small lesions, resulted in considerable increases in SUVmax, inhibiting the use of defined protocols for lesion classification based on SUVmax. However, reduced partial volume effects may increase lesion detectability. Matching SUVmax in phantoms translated well to patient studies for PSF reconstruction but less well with TOF, where a small positive bias was observed in patient images. Matching SUVmax significantly reduced voxel variance and potential variability of uptake measures. Finally, TLG may be less sensitive to reconstruction methods compared with either SUVmax or SUVpeak.

Accurate markerless respiratory tracking for gated whole body PET using the Microsoft Kinect

The motion due to respiration is responsible for greatly reducing image quality of whole body positron emission tomography, PET. A simple method to produce a respiratory signal to enable gating of PET listmode data using the Microsoft Kinect, a consumer grade 3D scanner, is presented. Phantom data produced by a sinusoidally oscillating phantom being tracked by an existing commercially available respiratory monitoring system and a Kinect based contactless tracking system shows that the Kinect system outperforms the Varian RPM tracking by producing higher resolution traces. When testing the Kinect using human subjects, the collected surface trace is sensitive enough to detect the patients heart rate. This has potential for improving motion correction of whole body imaging by including extra surface information provided by the Kinect, in addition to the basic respiratory signal.

The assessment of time-of-flight on image quality and quantification with reduced administered activity and scan times in 18F-FDG PET.

ObjectivesThe last decade has seen considerable technological innovations in PET detectors with the availability, among other advances, of time-of-flight (TOF). TOF has been shown to increase the signal-to-noise ratio (SNR), which should allow for a reduction in acquired counts while maintaining image quality. MethodsFifty-eight patients referred for routine 18F-flurodeoxyglucose (18F-FDG) oncology PET studies were included in this study. Patients with weight below or above 100 kg were prescribed 350 or 400 MBq of 18F-FDG, respectively. Listmode data were acquired for 2.5 min per bed position and reconstructed with ordered-subset expectation maximization (OSEM) reconstruction. TOF reconstruction was performed on reduced-count data, with two levels of reduction (−20 and −40% for patients <100 kg and −16 and −30% for patients >100 kg) achieved by clipping the listmode data. Liver SNR, mediastinum mean standardized uptake value (SUVmean), and lesion maximum standardized uptake value (SUVmax) were measured in all images. All images were visually assessed as adequate or suboptimal. ResultsNo significant difference was seen in mediastinum SUVmean or lesion SUVmax when comparing reduced-count TOF with full-count OSEM images. Compared with the original OSEM images, liver SNR was higher for TOF images using the more conservative −20% reduction of counts (P<0.001, Wilcoxon’s signed-rank test), whereas no significant statistical difference was seen with −40% reductions. ConclusionIncorporation of TOF allows for a reduction in acquired counts; this method has been implemented at our institution, with administered activity reduced for all patients to 280 MBq and a reduction in scan times for all but the largest patients. This has significantly reduced the patient radiation dose and improved scanner flexibility and throughput.

Apical thinning: real or artefact?

Background and objectiveApical thinning is a well-known phenomenon in myocardial perfusion SPECT, often attributed to reduced myocardial thickness at the apex of the left ventricle. Attenuation correction processing appears to exaggerate this effect. Although currently there is agreement that reduced apical counts are not a diagnostic indicator, opinions differ over the cause of this effect; we sought to clarify this using results from a phantom study. MethodsA commercially available anthropomorphic torso phantom was expanded using attachments mimicking tissue and bone to create three phantoms of increasing size. These were imaged using a dual-headed gamma camera and low-dose CT-based attenuation correction. The data were processed using iterative reconstruction, with and without attenuation correction. ResultsThe cardiac insert had a uniform wall thickness and yet defects characteristic of apical thinning appeared after attenuation correction, increasing in severity with phantom size. Before attenuation correction, a flare of activity was seen at the apex corresponding in position and size to the defect after attenuation correction. Further investigations showed the following: depth-dependent resolution was not responsible; the severity of the defect was more noticeably dependent on the addition of breast activity than the addition of attenuating material; the artefact was not unique to one particular algorithm; increasing the number of iterations reduced the severity of the artefact. ConclusionData acquisition and processing methods are thought to be responsible for the apparent apical defect. This phantom study therefore demonstrates that apical thinning is not simply an anatomical feature but can also be an artefact introduced by the use of attenuation correction.

Retention of 99mTc at Ultra-trace Levels in Flowing Column Experiments – Insights into Bioreduction and Biomineralization for Remediation at Nuclear Facilities

ABSTRACT The behavior of technetium at ultra-trace (<10−10 mol l−1) concentrations in bioreducing sediment column experiments was investigated using 99mTc γ-camera imaging. Four flowing sediment columns were biostimulated for varying periods of time, using acetate as an electron donor, such that on the day of imaging they represented oxic, early metal-reducing, Fe(III)-reducing and sulfate-reducing conditions. Prior to imaging, columns were spiked with 9.6 MBq of 99mTc(VII)O4−, which is relevant to the 99Tc mass concentrations observed at nuclear facilities, run under site relevant flow conditions, and imaged using γ-camera imaging at 20 min intervals over 12h. In the oxic column 99mTc behaved as a conservative tracer and did not interact significantly with the sediment. In all of the biostimulated columns 99mTc associated with the sediment although the spike was least mobile in the order sulfate < Fe(III)-reducing < early metal-reducing columns, confirming higher reactivity for 99mTc under increasingly reducing conditions. Columns were destructively sampled after 99mTc decay (5 days storage), and 0.5 N HCl extractable Fe as Fe(II) was measured at 2 cm intervals along the column length. The Fe(II) measured in all electron donor amended columns was present in stoichiometric excess to the 99mTc. Geochemical modelling and aqueous geochemical data from the different biostimulation treatments suggested that the elevated pH observed in the more reduced columns lead to increased sorbed and mineral associated Fe(II), both stronger reductants for Tc(VII) than aqueous Fe(II). In the sulfate reduction column the presence of FeS lead to the fastest rates of 99mTc immobilization. The results are the first to show the variable but significant retention of 99mTc at ultra-trace levels relevant to conditions at many nuclear sites in a range of biostimulated sediment columns and present a positive outlook for the treatment of 99Tc contaminated groundwater through in-situ biostimulation.

Accuracy and variability of quantitative measurements using PET with time-of-flight information and resolution modelling

Quantitative measurements are increasingly used in cancer staging and therapy monitoring. This work investigates the impact of resolution modeling and time-of-flight reconstruction on the accuracy and variability of two types of activity concentration (AC) measurements, mean and maximum, in spheres of different sizes and contrast. Results are compared with conventional OSEM reconstruction that does not include these additions. Positive bias was seen in nearly all maximum AC measurements, particularly with OSEM in larger, low contrast spheres with no or small amounts of post-filtering. Maximum AC was far less dependent on sphere size in high contrast with combined resolution modeling and time-of-flight. Resolution modeling and time-of-flight were shown to reduce the variability of maximum AC measurements for all sphere sizes and post-filters. Negative bias was seen in all mean AC measurements, with mean AC recovery being greatest in smaller spheres with resolution modeling and time-of-flight. Mean AC recovery was comparable in the larger spheres for all reconstruction algorithms. Either no or very small reductions in the variability of mean AC measurements were seen with resolution modeling and time-of-flight.

Quantifying technetium and strontium bioremediation potential in flowing sediment columns.

The high-yield fission products 99Tc and 90Sr are found as problematic radioactive contaminants in groundwater at nuclear sites. Treatment options for radioactively contaminated land include bioreduction approaches, and this paper explores 99mTc and 90Sr behavior and stability under a range of biogeochemical conditions stimulated by electron donor addition methods. Dynamic column experiments with sediment from the Sellafield nuclear facility, completed at site relevant flow conditions, demonstrated that Fe(III)-reducing conditions had developed by 60 days. Sediment reactivity toward 99Tc was then probed using a 99mTc(VII) tracer at <10-10 mol L-1 and γ camera imaging showed full retention of 99mTc in acetate amended systems. Sediment columns were then exposed to selected treatments to examine the effects of different acetate amendment regimes and reoxidation scenarios over 55 days when they were again imaged with 99mTc. Here, partially oxidized sediments with no further electron donor additions remained reactive toward 99mTc under relevant groundwater O2 and NO3- concentrations over 55 days. Immobilization of 99mTc was highest where continuous acetate amendment had resulted in sulfate-reducing conditions. Interestingly, the sulfate reducing system showed enhanced Sr retention when stable Sr2+ was added continuously as a proxy for 90Sr. Overall, sediment reactivity was nondestructively imaged over an extended period to provide new information about dynamic iron and radionuclide biogeochemistry throughout realistic sediment redox cycling regimes.

Optimising the transport properties and reactivity of microbially-synthesised magnetite for in situ remediation

Engineered nanoparticles offer the potential for remediation of land and water that has been contaminated by organics and metals. Microbially synthesized nano-scale magnetite, prepared from Fe(III) oxides by subsurface Fe(III)-reducing bacteria, offers a scalable biosynthesis route to such a nano-scale remediation reagent. To underpin delivery of “bionanomagnetite” (BNM) nanomaterial during in situ treatment options, we conducted a range of batch and column experiments to assess and optimise the transport and reactivity of the particles in porous media. Collectively these experiments, which include state of the art gamma imaging of the transport of 99m Tc-labelled BNM in columns, showed that non-toxic, low cost coatings such as guar gum and salts of humic acid can be used to enhance the mobility of the nanomaterial, while maintaining reactivity against target contaminants. Furthermore, BNM reactivity can be enhanced by the addition of surface coatings of nano-Pd, extending the operational lifetime of the BNM, in the presence of a simple electron donor such as hydrogen or formate.

Microbial impacts on 99mTc migration through sandstone under highly alkaline conditions relevant to radioactive waste disposal

Geological disposal of intermediate level radioactive waste in the UK is planned to involve the use of cementitious materials, facilitating the formation of an alkali-disturbed zone within the host rock. The biogeochemical processes that will occur in this environment, and the extent to which they will impact on radionuclide migration, are currently poorly understood. This study investigates the impact of biogeochemical processes on the mobility of the radionuclide technetium, in column experiments designed to be representative of aspects of the alkali-disturbed zone. Results indicate that microbial processes were capable of inhibiting 99mTc migration through columns, and X-ray radiography demonstrated that extensive physical changes had occurred to the material within columns where microbiological activity had been stimulated. The utilisation of organic acids under highly alkaline conditions, generating H2 and CO2, may represent a mechanism by which microbial processes may alter the hydraulic conductivity of a geological environment. Column sediments were dominated by obligately alkaliphilic H2-oxidising bacteria, suggesting that the enrichment of these bacteria may have occurred as a result of H2 generation during organic acid metabolism. The results from these experiments show that microorganisms are able to carry out a number of processes under highly alkaline conditions that could potentially impact on the properties of the host rock surrounding a geological disposal facility for intermediate level radioactive waste.