Showing papers in "EJNMMI Physics in 2016"

Recent developments in time-of-flight PET

Abstract: While the first time-of-flight (TOF)-positron emission tomography (PET) systems were already built in the early 1980s, limited clinical studies were acquired on these scanners. PET was still a research tool, and the available TOF-PET systems were experimental. Due to a combination of low stopping power and limited spatial resolution (caused by limited light output of the scintillators), these systems could not compete with bismuth germanate (BGO)-based PET scanners. Developments on TOF system were limited for about a decade but started again around 2000. The combination of fast photomultipliers, scintillators with high density, modern electronics, and faster computing power for image reconstruction have made it possible to introduce this principle in clinical TOF-PET systems. This paper reviews recent developments in system design, image reconstruction, corrections, and the potential in new applications for TOF-PET. After explaining the basic principles of time-of-flight, the difficulties in detector technology and electronics to obtain a good and stable timing resolution are shortly explained. The available clinical systems and prototypes under development are described in detail. The development of this type of PET scanner also requires modified image reconstruction with accurate modeling and correction methods. The additional dimension introduced by the time difference motivates a shift from sinogram- to listmode-based reconstruction. This reconstruction is however rather slow and therefore rebinning techniques specific for TOF data have been proposed. The main motivation for TOF-PET remains the large potential for image quality improvement and more accurate quantification for a given number of counts. The gain is related to the ratio of object size and spatial extent of the TOF kernel and is therefore particularly relevant for heavy patients, where image quality degrades significantly due to increased attenuation (low counts) and high scatter fractions. The original calculations for the gain were based on analytical methods. Recent publications for iterative reconstruction have shown that it is difficult to quantify TOF gain into one factor. The gain depends on the measured distribution, the location within the object, and the count rate. In a clinical situation, the gain can be used to either increase the standardized uptake value (SUV) or reduce the image acquisition time or administered dose. The localized nature of the TOF kernel makes it possible to utilize local tomography reconstruction or to separate emission from transmission data. The introduction of TOF also improves the joint estimation of transmission and emission images from emission data only. TOF is also interesting for new applications of PET-like isotopes with low branching ratio for positron fraction. The local nature also reduces the need for fine angular sampling, which makes TOF interesting for limited angle situations like breast PET and online dose imaging in proton or hadron therapy. The aim of this review is to introduce the reader in an educational way into the topic of TOF-PET and to give an overview of the benefits and new opportunities in using this additional information.

Physics of pure and non-pure positron emitters for PET: a review and a discussion

Abstract: With the increased interest in new PET tracers, gene-targeted therapy, immunoPET, and theranostics, other radioisotopes will be increasingly used in clinical PET scanners, in addition to 18F. Some of the most interesting radioisotopes with prospective use in the new fields are not pure short-range β+ emitters but can be associated with gamma emissions in coincidence with the annihilation radiation (prompt gamma), gamma-gamma cascades, intense Bremsstrahlung radiation, high-energy positrons that may escape out of the patient skin, and high-energy gamma rays that result in some e +/e − pair production. The high level of sophistication in data correction and excellent quantitative accuracy that has been reached for 18F in recent years can be questioned by these effects. In this work, we review the physics and the scientific literature and evaluate the effect of these additional phenomena on the PET data for each of a series of radioisotopes: 11C, 13N, 15O, 18F, 64Cu, 68Ga, 76Br, 82Rb, 86Y, 89Zr, 90Y, and 124I. In particular, we discuss the present complications arising from the prompt gammas, and we review the scientific literature on prompt gamma correction. For some of the radioisotopes considered in this work, prompt gamma correction is definitely needed to assure acceptable image quality, and several approaches have been proposed in recent years. Bremsstrahlung photons and 176Lu background were also evaluated.

An overview of CEST MRI for non-MR physicists

Abstract: The search for novel image contrasts has been a major driving force in the magnetic resonance (MR) research community, in order to gain further information on the body's physiological and pathological conditions.Chemical exchange saturation transfer (CEST) is a novel MR technique that enables imaging certain compounds at concentrations that are too low to impact the contrast of standard MR imaging and too low to directly be detected in MRS at typical water imaging resolution. For this to be possible, the target compound must be capable of exchanging protons with the surrounding water molecules. This property can be exploited to cause a continuous buildup of magnetic saturation of water, leading to greatly enhanced sensitivity.The goal of the present review is to introduce the basic principles of CEST imaging to the general molecular imaging community. Special focus has been given to the comparison of state-of-the-art CEST methods reported in the literature with their positron emission tomography (PET) counterparts.

Quantitative comparison of PET performance—Siemens Biograph mCT and mMR

Abstract: Integrated clinical whole-body PET/MR systems were introduced in 2010. In order to bring this technology into clinical usage, it is of great importance to compare the performance with the well-established PET/CT. The aim of this study was to evaluate PET performance, with focus on image quality, on Siemens Biograph mMR (PET/MR) and Siemens Biograph mCT (PET/CT). A direct quantitative comparison of the performance characteristics between the mMR and mCT system was performed according to National Electrical Manufacturers Association (NEMA) NU 2-2007 protocol. Spatial resolution, sensitivity, count rate and image quality were evaluated. The evaluation was supplemented with additional standardized uptake value (SUV) measurements. The spatial resolution was similar for the two systems. Average sensitivity was higher for the mMR (13.3 kcps/MBq) compared to the mCT system (10.0 kcps/MBq). Peak noise equivalent count rate (NECR) was slightly higher for the mMR (196 kcps @ 24.4 kBq/mL) compared to the mCT (186 kcps @ 30.1 kBq/mL). Scatter fractions in the clinical activity concentration range yielded lower values for the mCT (34.9 %) compared to those for the mMR (37.0 %). Best image quality of the systems resulted in approximately the same mean hot sphere contrast and a difference of 19 percentage points (pp) in mean cold contrast, in favour of the mCT. In general, point spread function (PSF) increased hot contrast and time of flight (TOF) increased both hot and cold contrast. Highest hot contrast for the smallest sphere (10 mm) was achieved with the combination of TOF and PSF on the mCT. Lung residual error was higher for the mMR (22 %) than that for the mCT (17 %), with no effect of PSF. With TOF, lung residual error was reduced to 8 % (mCT). SUV was accurate for both systems, but PSF caused overestimations for the 13-, 17- and 22-mm spheres. Both systems proved good performance characteristics, and the PET image quality of the mMR was close to that of the mCT. Differences between the systems were mainly due to the TOF possibility on the mCT, which resulted in an overall better image quality, especially for the most challenging settings with higher background activity and small uptake volumes.

Abdo-Man: a 3D-printed anthropomorphic phantom for validating quantitative SIRT

Abstract: The use of selective internal radiation therapy (SIRT) is rapidly increasing, and the need for quantification and dosimetry is becoming more widespread to facilitate treatment planning and verification. The aim of this project was to develop an anthropomorphic phantom that can be used as a validation tool for post-SIRT imaging and its application to dosimetry. The phantom design was based on anatomical data obtained from a T1-weighted volume-interpolated breath-hold examination (VIBE) on a Siemens Aera 1.5 T MRI scanner. The liver, lungs and abdominal trunk were segmented using the Hermes image processing workstation. Organ volumes were then uploaded to the Delft Visualization and Image processing Development Environment for smoothing and surface rendering. Triangular meshes defining the iso-surfaces were saved as stereo lithography (STL) files and imported into the Autodesk® Meshmixer software. Organ volumes were subtracted from the abdomen and a removable base designed to allow access to the liver cavity. Connection points for placing lesion inserts and filling holes were also included. The phantom was manufactured using a Stratasys Connex3 PolyJet 3D printer. The printer uses stereolithography technology combined with ink jet printing. Print material is a solid acrylic plastic, with similar properties to polymethylmethacrylate (PMMA). Measured Hounsfield units and calculated attenuation coefficients of the material were shown to also be similar to PMMA. Total print time for the phantom was approximately 5 days. Initial scans of the phantom have been performed with Y-90 bremsstrahlung SPECT/CT, Y-90 PET/CT and Tc-99m SPECT/CT. The CT component of these images compared well with the original anatomical reference, and measurements of volume agreed to within 9 %. Quantitative analysis of the phantom was performed using all three imaging techniques. Lesion and normal liver absorbed doses were calculated from the quantitative images in three dimensions using the local deposition method. 3D printing is a flexible and cost-efficient technology for manufacture of anthropomorphic phantom. Application of such phantoms will enable quantitative imaging and dosimetry methodologies to be evaluated, which with optimisation could help improve outcome for patients.

A novel planar image-based method for bone marrow dosimetry in 177 Lu-DOTATATE treatment correlates with haematological toxicity

Abstract: 177Lu-DOTATATE is a valuable treatment option for patients with advanced neuroendocrine tumours overexpressing somatostatin receptors. Though well tolerated in general, bone marrow toxicity can, besides renal exposure, become dose limiting and affect the ability to sustain future therapies. The aim of this study was to develop a novel planar image-based method for bone marrow dosimetry and evaluate its correlation with haematological toxicity during 177Lu-DOTATATE treatment. In this study, 46 patients with advanced neuroendocrine tumours were treated with 7.2 GBq (3.5–8.3 GBq) of 177Lu-DOTATATE on two to five occasions. Planar gamma camera images were acquired at 2, 24, 48 and 168 h post-injection. Whole-body regions of interest were created in the images, and a threshold-based segmentation algorithm was applied to separate the uptake of 177Lu-DOTATATE into high and low uptake compartments. The conjugate view method was used to quantify the activity, the accumulated activity was calculated and the absorbed dose to the bone marrow was estimated according to the MIRD scheme. Patients were monitored for haematological toxicity based on haemoglobin (Hb), white blood cell (WBC) and platelet (PLT) counts every other week during the treatment period. The mean absorbed dose to the bone marrow was estimated to 0.20 Gy (0.11–0.37 Gy) per 7.4 GBq of 177Lu-DOTATATE, and the mean dose per fraction correlated with a decrease in Hb (p = 0.01), WBC (p < 0.01) and PLT (p < 0.01) counts. The total mean absorbed dose to the bone marrow was 0.64 Gy (0.30–1.5 Gy) per 24 GBq (8.2–37 GBq) of 177Lu-DOTATATE and also correlated with a decrease in Hb (p < 0.01), WBC (p = 0.01) and PLT (p < 0.01) counts. The planar image-based method developed in this study resulted in similar absorbed doses to the bone marrow as reported in earlier studies with blood-based bone marrow dosimetry. The results correlated with haematological toxicity, making it a promising method for estimating bone marrow doses in 177Lu-DOTATATE treatment without the need for blood and urine sampling.

CADA-computer-aided DaTSCAN analysis.

Abstract: Dopamine transporter (DaT) imaging (DaTSCAN) is useful for the differential diagnosis of parkinsonian syndromes. Visual evaluation of DaTSCAN images represents the generally accepted diagnostic method, but it is strongly dependent on the observer’s experience and shows inter- and intra-observer variability. A reliable and automatic method for DaTSCAN evaluation can provide objective quantification; it is desirable for longitudinal studies, and it allows for a better follow-up control. Moreover, it is crucial for an automated method to produce coherent measures related to the severity of motor symptoms. In this work, we propose a novel fully automated technique for DaTSCAN analysis that generates quantitative measures based on striatal intensity, shape, symmetry and extent. We tested these measures using a support vector machine (SVM) classifier. The proposed measures reached 100 % accuracy in distinguishing between patients with Parkinson’s disease (PD) and control subjects. We also demonstrate the existence of a linear relationship and an exponential trend between pooled structural and functional striatal characteristics and the Unified Parkinson’s disease Rating Scale (UPDRS) motor score. We present a novel, highly reproducible, user-independent technique for DaTSCAN analysis producing quantitative measures directly connected to striatum uptake and shape. In our method, no a priori assumption is required on the spatial conformation and localization of striatum, and both uptake and symmetry contribute to the index quantification. These measures can reliably support a computer-assisted decision system.

Radiation exposure of the spleen during 177 Lu-DOTATATE treatment and its correlation with haematological toxicity and spleen volume

Abstract: Somatostatin analogue-based radionuclide therapy with 177Lu-DOTATATE is an important treatment option for patients with advanced neuroendocrine tumours overexpressing somatostatin receptors. In addition to the kidneys, the bone marrow is a major dose-limiting organ. The correlation between developed haematological toxicity and absorbed dose to the bone marrow is poor, which indicates that other factors affect haematological response. The spleen has an important role in the haematopoetic system, including being a reservoir for blood cells. It is also the organ that receives the highest mean absorbed dose during 177Lu-DOTATATE treatment. The aim of this study was to analyse mean absorbed dose to the spleen and its correlation with haematological toxicity, and to explore changes in splenic volume. The study included 41 patients treated with 7.2 GBq (3.5–8.3 GBq) of 177Lu-DOTATATE on two to five occasions. Following each fraction, planar whole-body scans were acquired at 2, 24, 48, and 168 h, and a SPECT/CT at 24 h post-injection. Mean absorbed spleen dose was calculated utilising planar images for time-activity data and SPECT to adjust activity amounts. Splenic volume information was collected from diagnostic CT scans at baseline and follow-up. Median and total absorbed spleen doses were estimated to 4.5 and 15 Gy, respectively. Total absorbed spleen dose correlated with decrease in Hb (p = 0.02), but not WBC (p = 0.31) or PLT (p = 0.65) counts. For patients without bone metastases, mean absorbed spleen dose correlated with decrease in PLT (p = 0.04) but not Hb (p = 0.16) or WBC (p = 0.42) counts. The spleen volume was reduced to 75 % (p < 0.001) of original values (200 vs. 260 ml) at a mean follow-up of 36 months. Haematological toxicity according to Hb counts was moderately but significantly correlated with total absorbed spleen dose. This supports the possibility that radiation exposure of the spleen affects overall haematological response during 177Lu-DOTATATE treatment.

Phantom criteria for qualification of brain FDG and amyloid PET across different cameras.

Abstract: While fluorodeoxyglucose (FDG) and amyloid PET is valuable for patient management, research, and clinical trial of therapeutics on Alzheimer’s disease, the specific details of the PET scanning method including the PET camera model type influence the image quality, which may further affect the interpretation of images and quantitative capabilities. To make multicenter PET data reliable and to establish PET scanning as a universal diagnostic technique and a verified biomarker, we have proposed phantom test procedures and criteria for optimizing image quality across different PET cameras. As the method, four physical parameters (resolution, gray-white contrast, uniformity, and image noise) were selected as essential to image quality for brain FDG and amyloid PET and were measured with a Hoffman 3D brain phantom and a uniform cylindrical phantom on a total of 12 currently used PET models. The phantom radioactivity and acquisition time were determined based on the standard scanning protocol for each PET drug (FDG, 11C-PiB, 18F-florbetapir, and 18F-flutemetamol). Reconstruction parameters were either determined based on the methods adopted in ADNI, J-ADNI, and other research and clinical trials or optimized based on measured phantom image parameters under various reconstruction conditions. As the result, phantom test criteria were proposed as follows: (i) 8 mm FWHM or better resolution and (ii) gray/white %contrast ≥55 % with the Hoffman 3D brain phantom and (iii) SD of 51 small region of interests (ROIs) ≤0.0249 (equivalent to 5 % variation) for uniformity and (iv) image noise (SD/mean) ≤15 % for a large ROI with the uniform cylindrical phantom. These criteria provided image quality conforming to those multicenter clinical studies and were also achievable with most of the PET cameras that are currently used. The proposed phantom test criteria facilitate standardization and qualification of brain FDG and amyloid PET images and deserve further evaluation by future multicenter clinical studies.

Organ-specific SPECT activity calibration using 3D printed phantoms for molecular radiotherapy dosimetry.

Abstract: Patient-specific absorbed dose calculations for molecular radiotherapy require accurate activity quantification. This is commonly derived from Single-Photon Emission Computed Tomography (SPECT) imaging using a calibration factor relating detected counts to known activity in a phantom insert. A series of phantom inserts, based on the mathematical models underlying many clinical dosimetry calculations, have been produced using 3D printing techniques. SPECT/CT data for the phantom inserts has been used to calculate new organ-specific calibration factors for 99m Tc and 177Lu. The measured calibration factors are compared to predicted values from calculations using a Gaussian kernel. Measured SPECT calibration factors for 3D printed organs display a clear dependence on organ shape for 99m Tc and 177Lu. The observed variation in calibration factor is reproduced using Gaussian kernel-based calculation over two orders of magnitude change in insert volume for 99m Tc and 177Lu. These new organ-specific calibration factors show a 24, 11 and 8 % reduction in absorbed dose for the liver, spleen and kidneys, respectively. Non-spherical calibration factors from 3D printed phantom inserts can significantly improve the accuracy of whole organ activity quantification for molecular radiotherapy, providing a crucial step towards individualised activity quantification and patient-specific dosimetry. 3D printed inserts are found to provide a cost effective and efficient way for clinical centres to access more realistic phantom data.

Technical note: how to determine the FDG activity for tumour PET imaging that satisfies European guidelines

Abstract: For tumour imaging with PET, the literature proposes to administer a patient-specific FDG activity that depends quadratically on a patient’s body weight. However, a practical approach on how to implement such a protocol in clinical practice is currently lacking. We aimed to provide a practical method to determine a FDG activity formula for whole-body PET examinations that satisfies both the EANM guidelines and this quadratic relation. We have developed a methodology that results in a formula describing the patient-specific FDG activity to administer. A PET study using the NEMA NU-2001 image quality phantom forms the basis of our method. This phantom needs to be filled with 2.0 and 20.0 kBq FDG/mL in the background and spheres, respectively. After a PET acquisition of 10 min, a reconstruction has to be performed that results in sphere recovery coefficients (RCs) that are within the specifications as defined by the EANM Research Ltd (EARL). By performing reconstructions based on shorter scan durations, the minimal scan time per bed position (T min) needs to be extracted using an image coefficient of variation (COV) of 15 %. At T min, the RCs should be within EARL specifications as well. Finally, the FDG activity (in MBq) to administer can be described by $$ A=c \cdot {w}^2\cdot \frac{T_{\min }}{t} $$ with c a constant that is typically 0.0533 (MBq/kg2), w the patient’s body weight (in kg), and t the scan time per bed position that is chosen in a clinical setting (in seconds). We successfully demonstrated this methodology using a state-of-the-art PET/CT scanner. We provide a practical method that results in a formula describing the FDG activity to administer to individual patients for whole-body PET examinations, taking into account both the EANM guidelines and a quadratic relation between FDG activity and patient’s body weight. This formula is generally applicable to any PET system, using a specified image reconstruction and scan time per bed position.

Optimization of brain PET imaging for a multicentre trial: the French CATI experience

Abstract: Background CATI is a French initiative launched in 2010 to handle the neuroimaging of a large cohort of subjects recruited for an Alzheimer’s research program called MEMENTO. This paper presents our test protocol and results obtained for the 22 PET centres (overall 13 different scanners) involved in the MEMENTO cohort. We determined acquisition parameters using phantom experiments prior to patient studies, with the aim of optimizing PET quantitative values to the highest possible per site, while reducing, if possible, variability across centres.

Left ventricular function assessment using 123I/99mTc dual-isotope acquisition with two semi-conductor cadmium-zinc-telluride (CZT) cameras: a gated cardiac phantom study.

Abstract: The impact of increased energy resolution of cadmium–zinc–telluride (CZT) cameras on the assessment of left ventricular function under dual-isotope conditions (99mTc and 123I) remains unknown. The Amsterdam-gated dynamic cardiac phantom (AGATE, Vanderwilt techniques, Boxtel, The Netherlands) was successively filled with a solution of 123I alone, 99mTc alone, and a mixture of 123I and 99mTc. A total of 12 datasets was acquired with each commercially available CZT camera (DNM 530c, GE Healthcare and DSPECT, Biosensors International) using both energy windows (99mTc or 123I) with ejection fraction set to 33, 45, and 60 %. End-diastolic (EDV) and end-systolic (ESV) volumes, ejection fraction (LVEF), and regional wall motion and thickening (17-segment model) were assessed using Cedars-Sinai QGS Software. Concordance between single- and dual-isotope acquisitions was tested using Lin’s concordance correlation coefficient (CCC) and Bland–Altman plots. There was no significant difference between single- or simultaneous dual-isotope acquisition (123I and 99mTc) for EDV, ESV, LVEF, or segmental wall motion and thickening. Myocardial volumes using single- (123I, 99mTc) and dual-isotope (reconstructed using both 123I and 99mTc energy windows) acquisitions were, respectively, the following: EDV (mL) 88 ± 27 vs. 89 ± 27 vs. 92 ± 29 vs. 90 ± 26 for DNM 530c (p = NS) and 82 ± 20 vs. 83 ± 22 vs. 79 ± 19 vs. 77 ± 20 for DSPECT (p = NS); ESV (mL) 40 ± 1 vs. 41 ± 2 vs. 41 ± 2 vs. 42 ± 1 for DNM 530c (p = NS) and 37 ± 5 vs. 37 ± 1 vs. 35 ± 3 vs. 34 ± 2 for DSPECT (p = NS); LVEF (%) 52 ± 14 vs. 51 ± 13 vs. 53 ± 13 vs. 51 ± 13 for DNM 530c (p = NS) and 52 ± 16 vs. 54 ± 13 vs. 54 ± 14 vs. 54 ± 13 for DSPECT (p = NS); regional motion (mm) 6.72 ± 2.82 vs. 6.58 ± 2.52 vs. 6.86 ± 2.99 vs. 6.59 ± 2.76 for DNM 530c (p = NS) and 6.79 ± 3.17 vs. 6.81 ± 2.75 vs. 6.71 ± 2.50 vs. 6.62 ± 2.74 for DSPECT (p = NS). The type of camera significantly impacted only on ESV (p < 0.001). The new CZT cameras yielded similar results for the assessment of LVEF and regional motion using different energy windows (123I or 99mTc) and acquisition types (single vs. dual). With simultaneous dual-isotope acquisitions, the presence of 123I did not impact on LVEF assessment within the 99mTc energy window for either CZT camera.

A 3D-printed anatomical pancreas and kidney phantom for optimizing SPECT/CT reconstruction settings in beta cell imaging using 111In-exendin.

Abstract: Quantitative single photon emission computed tomography (SPECT) is challenging, especially for pancreatic beta cell imaging with 111In-exendin due to high uptake in the kidneys versus much lower uptake in the nearby pancreas. Therefore, we designed a three-dimensionally (3D) printed phantom representing the pancreas and kidneys to mimic the human situation in beta cell imaging. The phantom was used to assess the effect of different reconstruction settings on the quantification of the pancreas uptake for two different, commercially available software packages. 3D-printed, hollow pancreas and kidney compartments were inserted into the National Electrical Manufacturers Association (NEMA) NU2 image quality phantom casing. These organs and the background compartment were filled with activities simulating relatively high and low pancreatic 111In-exendin uptake for, respectively, healthy humans and type 1 diabetes patients. Images were reconstructed using Siemens Flash 3D and Hermes Hybrid Recon, with varying numbers of iterations and subsets and corrections. Images were visually assessed on homogeneity and artefacts, and quantitatively by the pancreas-to-kidney activity concentration ratio. Phantom images were similar to clinical images and showed comparable artefacts. All corrections were required to clearly visualize the pancreas. Increased numbers of subsets and iterations improved the quantitative performance but decreased homogeneity both in the pancreas and the background. Based on the phantom analyses, the Hybrid Recon reconstruction with 6 iterations and 16 subsets was found to be most suitable for clinical use. This work strongly contributed to quantification of pancreatic 111In-exendin uptake. It showed how clinical images of 111In-exendin can be interpreted and enabled selection of the most appropriate protocol for clinical use.

Fully automated calculation of image-derived input function in simultaneous PET/MRI in a sheep model

Abstract: Obtaining the arterial input function (AIF) from image data in dynamic positron emission tomography (PET) examinations is a non-invasive alternative to arterial blood sampling. In simultaneous PET/magnetic resonance imaging (PET/MRI), high-resolution MRI angiographies can be used to define major arteries for correction of partial-volume effects (PVE) and point spread function (PSF) response in the PET data. The present study describes a fully automated method to obtain the image-derived input function (IDIF) in PET/MRI. Results are compared to those obtained by arterial blood sampling. To segment the trunk of the major arteries in the neck, a high-resolution time-of-flight MRI angiography was postprocessed by a vessel-enhancement filter based on the inertia tensor. Together with the measured PSF of the PET subsystem, the arterial mask was used for geometrical deconvolution, yielding the time-resolved activity concentration averaged over a major artery. The method was compared to manual arterial blood sampling at the hind leg of 21 sheep (animal stroke model) during measurement of blood flow with O15-water. Absolute quantification of activity concentration was compared after bolus passage during steady state, i.e., between 2.5- and 5-min post injection. Cerebral blood flow (CBF) values from blood sampling and IDIF were also compared. The cross-calibration factor obtained by comparing activity concentrations in blood samples and IDIF during steady state is 0.98 ± 0.10. In all examinations, the IDIF provided a much earlier and sharper bolus peak than in the time course of activity concentration obtained by arterial blood sampling. CBF using the IDIF was 22 % higher than CBF obtained by using the AIF yielded by blood sampling. The small deviation between arterial blood sampling and IDIF during steady state indicates that correction of PVE and PSF is possible with the method presented. The differences in bolus dynamics and, hence, CBF values can be explained by the different sampling locations (hind leg vs. major neck arteries) with differences in delay/dispersion. It will be the topic of further work to test the method on humans with the perspective of replacing invasive blood sampling by an IDIF using simultaneous PET/MRI.

A novel statistical analysis method to improve the detection of hepatic foci of (111)In-octreotide in SPECT/CT imaging.

Abstract: Low uptake ratios, high noise, poor resolution, and low contrast all combine to make the detection of neuroendocrine liver tumours by 111In-octreotide single photon emission tomography (SPECT) imaging a challenge. The aim of this study was to develop a segmentation analysis method that could improve the accuracy of hepatic neuroendocrine tumour detection. Our novel segmentation was benchmarked by a retrospective analysis of patients categorized as either 111In-octreotide positive (111In-octreotide(+)) or 111In-octreotide negative (111In-octreotide(−)) for liver tumours. Following a 3-year follow-up period, involving multiple imaging modalities, we further segregated 111In-octreotide-negative patients into two groups: one with no confirmed liver tumours (111In-octreotide(−)/radtech(−)) and the other, now diagnosed with liver tumours (111In-octreotide(−)/radtech(+)). We retrospectively applied our segmentation analysis to see if it could have detected these previously missed tumours using 111In-octreotide. Our methodology subdivided the liver and determined normalized numbers of uptake foci (nNUF), at various threshold values, using a connected-component labelling algorithm. Plots of nNUF against the threshold index (ThI) were generated. ThI was defined as follows: ThI = (c max − c thr)/c max, where c max is the maximal threshold value for obtaining at least one, two voxel sized, uptake focus; c thr is the voxel threshold value. The maximal divergence between the nNUF values for 111In-octreotide(−)/radtech(−), and 111In-octreotide(+) livers, was used as the optimal nNUF value for tumour detection. We also corrected for any influence of the mean activity concentration on ThI. The nNUF versus ThI method (nNUFTI) was then used to reanalyze the 111In-octreotide(−)/radtech(−) and 111In-octreotide(−)/radtech(+) groups. Of a total of 53 111In-octreotide(−) patients, 40 were categorized as 111In-octreotide(−)/radtech(−) and 13 as 111In-octreotide(−)/radtech(+) group. Optimal separation of the nNUF values for 111In-octreotide(−)/radtech(−) and 111In-octreotide(+) groups was defined at the nNUF value of 0.25, to the right of the bell shaped nNUFTI curve. ThIs at this nNUF value were dependent on the mean activity concentration and therefore normalized to generate nThI; a significant difference in nThI values was found between the 111In-octreotide(−)/radtech(−) and the 111In-octreotide(−)/radtech(+) groups (P < 0.01). As a result, four of the 13 111In-octreotide(−)/radtech(+) livers were redesigned as 111In-octreotide(+). The nNUFTI method has the potential to improve the diagnosis of liver tumours using 111In-octreotide.

Radiation dosimetry of the α 4 β 2 nicotinic receptor ligand (+)-[ 18 F]flubatine, comparing preclinical PET/MRI and PET/CT to first-in-human PET/CT results

Abstract: Both enantiomers of [18F]flubatine are new radioligands for neuroimaging of α4β2 nicotinic acetylcholine receptors with positron emission tomography (PET) exhibiting promising pharmacokinetics which makes them attractive for different clinical questions. In a previous preclinical study, the main advantage of (+)-[18F]flubatine compared to (−)-[18F]flubatine was its higher binding affinity suggesting that (+)-[18F]flubatine might be able to detect also slight reductions of α4β2 nAChRs and could be more sensitive than (−)-[18F]flubatine in early stages of Alzheimer’s disease. To support the clinical translation, we investigated a fully image-based internal dosimetry approach for (+)-[18F]flubatine, comparing mouse data collected on a preclinical PET/MRI system to piglet and first-in-human data acquired on a clinical PET/CT system. Time-activity curves (TACs) were obtained from the three species, the animal data extrapolated to human scale, exponentially fitted and the organ doses (OD), and effective dose (ED) calculated with OLINDA. The excreting organs (urinary bladder, kidneys, and liver) receive the highest organ doses in all species. Hence, a renal/hepatobiliary excretion pathway can be assumed. In addition, the ED conversion factors of 12.1 μSv/MBq (mice), 14.3 μSv/MBq (piglets), and 23.0 μSv/MBq (humans) were calculated which are well within the order of magnitude as known from other 18F-labeled radiotracers. Although both enantiomers of [18F]flubatine exhibit different binding kinetics in the brain due to the respective affinities, the effective dose revealed no enantiomer-specific differences among the investigated species. The preclinical dosimetry and biodistribution of (+)-[18F]flubatine was shown and the feasibility of a dose assessment based on image data acquired on a small animal PET/MR and a clinical PET/CT was demonstrated. Additionally, the first-in-human study confirmed the tolerability of the radiation risk of (+)-[18F]flubatine imaging which is well within the range as caused by other 18F-labeled tracers. However, as shown in previous studies, the ED in humans is underestimated by up to 50 % using preclinical imaging for internal dosimetry. This fact needs to be considered when applying for first-in-human studies based on preclinical biokinetic data scaled to human anatomy.

Evaluation of spatial dependence of point spread function-based PET reconstruction using a traceable point-like 22 Na source

Abstract: The point spread function (PSF) of positron emission tomography (PET) depends on the position across the field of view (FOV). Reconstruction based on PSF improves spatial resolution and quantitative accuracy. The present study aimed to quantify the effects of PSF correction as a function of the position of a traceable point-like 22Na source over the FOV on two PET scanners with a different detector design. We used Discovery 600 and Discovery 710 (GE Healthcare) PET scanners and traceable point-like 22Na sources (<1 MBq) with a spherical absorber design that assures uniform angular distribution of the emitted annihilation photons. The source was moved in three directions at intervals of 1 cm from the center towards the peripheral FOV using a three-dimensional (3D)-positioning robot, and data were acquired over a period of 2 min per point. The PET data were reconstructed by filtered back projection (FBP), the ordered subset expectation maximization (OSEM), OSEM + PSF, and OSEM + PSF + time-of-flight (TOF). Full width at half maximum (FWHM) was determined according to the NEMA method, and total counts in regions of interest (ROI) for each reconstruction were quantified. The radial FWHM of FBP and OSEM increased towards the peripheral FOV, whereas PSF-based reconstruction recovered the FWHM at all points in the FOV of both scanners. The radial FWHM for PSF was 30–50 % lower than that of OSEM at the center of the FOV. The accuracy of PSF correction was independent of detector design. Quantitative values were stable across the FOV in all reconstruction methods. The effect of TOF on spatial resolution and quantitation accuracy was less noticeable. The traceable 22Na point-like source allowed the evaluation of spatial resolution and quantitative accuracy across the FOV using different reconstruction methods and scanners. PSF-based reconstruction reduces dependence of the spatial resolution on the position. The quantitative accuracy over the entire FOV of the PET system is good, regardless of the reconstruction methods, although it depends slightly on the position.

Pharmacokinetic modeling of a novel hypoxia PET tracer [18F]HX4 in patients with non-small cell lung cancer.

Abstract: [18F]HX4 is a promising new PET tracer developed to identify hypoxic areas in tumor tissue. This study analyzes [18F]HX4 kinetics and assesses the performance of simplified methods for quantification of [18F]HX4 uptake. To this end, eight patients with non-small cell lung cancer received dynamic PET scans at three different time points (0, 120, and 240 min) after injection of 426 ± 72 MBq [18F]HX4, each lasting 30 min. Several compartment models were fitted to time activity curves (TAC) derived from various areas within tumor tissue using image-derived input functions. Best fits were obtained using the reversible two-tissue compartment model with blood volume parameter (2T4k+VB). Simplified measures correlated well with VT estimates (tumor-to-blood ratio (TBr) R 2 = 0.96, tumor-to-muscle ratio R 2 = 0.94, standardized uptake value R 2 = 0.89). [18F]HX4 shows reversible kinetics in tumor tissue: 2T4k+VB. TBr based on static imaging at 2 or 4 h can be used for quantification of [18F]HX4 uptake.

Simultaneous PET/MRI with 13C magnetic resonance spectroscopic imaging (hyperPET): phantom-based evaluation of PET quantification

Abstract: Background Integrated PET/MRI with hyperpolarized 13C magnetic resonance spectroscopic imaging (13C-MRSI) offers simultaneous, dual-modality metabolic imaging. A prerequisite for the use of simultaneous imaging is the absence of interference between the two modalities. This has been documented for a clinical whole-body system using simultaneous 1H-MRI and PET but never for 13C-MRSI and PET. Here, the feasibility of simultaneous PET and 13C-MRSI as well as hyperpolarized 13C-MRSI in an integrated whole-body PET/MRI hybrid scanner is evaluated using phantom experiments.

Simultaneous Tc-99m and I-123 dual-radionuclide imaging with a solid-state detector-based brain-SPECT system and energy-based scatter correction

Abstract: A brain single-photon emission computed tomography (SPECT) system using cadmium telluride (CdTe) solid-state detectors was previously developed. This CdTe-SPECT system is suitable for simultaneous dual-radionuclide imaging due to its fine energy resolution (6.6 %). However, the problems of down-scatter and low-energy tail due to the spectral characteristics of a pixelated solid-state detector should be addressed. The objective of this work was to develop a system for simultaneous Tc-99m and I-123 brain studies and evaluate its accuracy. A scatter correction method using five energy windows (FiveEWs) was developed. The windows are Tc-lower, Tc-main, shared sub-window of Tc-upper and I-lower, I-main, and I-upper. This FiveEW method uses pre-measured responses for primary gamma rays from each radionuclide to compensate for the overestimation of scatter by the triple-energy window method that is used. Two phantom experiments and a healthy volunteer experiment were conducted using the CdTe-SPECT system. A cylindrical phantom and a six-compartment phantom with five different mixtures of Tc-99m and I-123 and a cold one were scanned. The quantitative accuracy was evaluated using 18 regions of interest for each phantom. In the volunteer study, five healthy volunteers were injected with Tc-99m human serum albumin diethylene triamine pentaacetic acid (HSA-D) and scanned (single acquisition). They were then injected with I-123 N-isopropyl-4-iodoamphetamine hydrochloride (IMP) and scanned again (dual acquisition). The counts of the Tc-99m images for the single and dual acquisitions were compared. In the cylindrical phantom experiments, the percentage difference (PD) between the single and dual acquisitions was 5.7 ± 4.0 % (mean ± standard deviation). In the six-compartment phantom experiment, the PDs between measured and injected activity for Tc-99m and I-123 were 14.4 ± 11.0 and 2.3 ± 1.8 %, respectively. In the volunteer study, the PD between the single and dual acquisitions was 4.5 ± 3.4 %. This CdTe-SPECT system using the FiveEW method can provide accurate simultaneous dual-radionuclide imaging. A solid-state detector SPECT system using the FiveEW method will permit quantitative simultaneous Tc-99m and I-123 study to become clinically applicable.

A study of SPECT/CT camera stability for quantitative imaging

Abstract: The purpose of this study was twofold: to evaluate the quantitative stability of a SPECT/CT gamma camera over time and to determine if daily flood acquisitions can reliably serve as calibration factors for quantitative SPECT. Using a cylindrical water phantom filled with measured amounts of 99mTc, factors were calculated to convert counts/cc to activity/cps. Measurements were made over an 18-month period. System sensitivity data calculated from 57Co daily quality assurance (DQA) flood acquisitions were then compared to the 99mTc calibration factors to determine the relationship of the factors. The coefficient of variation is 2.7 % for the 99mTc cylinder conversion factors and 2.6 % for the 57Co DQA flood data. The greatest difference between the cylinder conversion factors and the flood data is less than 3 %. Based on the results, the camera was stable within 3 % over an 18-month time period. The daily flood source acquisitions can be a reliable source for tracking camera stability and may provide information on updating the calibration factor for quantitative imaging.

Effect of dosimeter's position on occupational radiation extremity dose measurement for nuclear medicine workers during (18)F-FDG preparation for PET/CT.

Abstract: The recent spread of positron emission tomography-computed tomography (PET/CT) poses extremity dosimetry challenges. The question arose whether the radiation dose measured by the ring thermoluminescent dosimeter usually worn on the proximal phalanx (P1) of the index finger measures doses that are representative of the true doses received by the upper extremities of the operators. A prospective individual dosimetry study was performed in which the personal equivalent dose Hp (0.07) received during a specific 2-[18F]fluoro-2-deoxy-d-glucose (18F-FDG) manual dose-dispensing procedure was measured in a paired design by two operational personal electronic dosimeters fitted on the palm side of the index finger, namely in the P1 and distal phalanx (P3) positions. The study participants were ten nuclear medicine technologists working in two nuclear medicine departments. The personal equivalent radiation doses received by the palm side of the proximal phalanx of the index finger [Hp (0.07)P1] and that received by the distal phalanx [Hp (0.07)P3] were compared. The median Hp (0.07)P3/Hp (0.07)P1 ratio per participant varied between 1.0 and 2.5 (based on 23 to 31 measurements per participant). The 271 paired measurements revealed a crude Hp (0.07)P3/Hp (0.07)P1 ratio of 1.67, significantly different from 1 (p = 0.0004, 95 % CI [1.35–2.07]). When adjusted on participant’s gender and mother vial activity, the ratio was similar (1.53, p = 0.003, 95 % CI [1.22–1.92]). The study demonstrated a significant disparity that may exist between the radiation doses measured in the P1 and P3 positions of operators during 18F-FDG manipulation. These findings emphasize the importance of performing workplace dosimetry studies adapted to each radiopharmaceutical and manipulation thereof, aiming to guarantee optimal workers’ dosimetry monitoring schemes. Hospital Nursing and Paramedical Research Program (PHRIP, 2011–2013) from the French Ministry of Health (DGOS), http://social-sante.gouv.fr/IMG/pdf/Resultats_PHRIP_2011.pdf

A gamma-distribution convolution model of 99m Tc-MIBI thyroid time-activity curves

Abstract: The convolution approach to thyroid time-activity curve (TAC) data fitting with a gamma distribution convolution (GDC) TAC model following bolus intravenous injection is presented and applied to 99mTc-MIBI data. The GDC model is a convolution of two gamma distribution functions that simultaneously models the distribution and washout kinetics of the radiotracer. The GDC model was fitted to thyroid region of interest (ROI) TAC data from 1 min per frame 99mTc-MIBI image series for 90 min; GDC models were generated for three patients having left and right thyroid lobe and total thyroid ROIs, and were contrasted with washout-only models, i.e., less complete models. GDC model accuracy was tested using 10 Monte Carlo simulations for each clinical ROI. The nine clinical GDC models, obtained from least counting error of counting, exhibited corrected (for 6 parameters) fit errors ranging from 0.998% to 1.82%. The range of all thyroid mean residence times (MRTs) was 212 to 699 min, which from noise injected simulations of each case had an average coefficient of variation of 0.7% and a not statistically significant accuracy error of 0.5% (p = 0.5, 2-sample paired t test). The slowest MRT value (699 min) was from a single thyroid lobe with a tissue diagnosed parathyroid adenoma also seen on scanning as retained marker. The two total thyroid ROIs without substantial pathology had MRT values of 278 and 350 min overlapping a published 99mTc-MIBI thyroid MRT value. One combined value and four unrelated washout-only models were tested and exhibited R-squared values for MRT with the GDC, i.e., a more complete concentration model, ranging from 0.0183 to 0.9395. The GDC models had a small enough TAC noise-image misregistration (0.8%) that they have a plausible use as simulations of thyroid activity for querying performance of other models such as washout models, for altered ROI size, noise, administered dose, and image framing rates. Indeed, of the four washout-only models tested, no single model approached the apparent accuracy of the GDC model using only 90 min of data. Ninety minutes is a long gamma-camera acquisition time for a patient, but a short a time for most kinetic models. Consequently, the results should be regarded as preliminary.

Measurement of cardiovascular function using a novel view-sharing PET reconstruction method and tracer kinetic analysis

Abstract: Recent advancements in PET instrumentation have made the non-invasive assessment of cardiovascular function in small animals a reality. The majority of small animal PET systems use stationary detector gantries, thus affording high temporal resolution imaging of cardiac function. Systems designed to maximize spatial resolution and detection sensitivity employing rotating gantry designs are suboptimal when high temporal resolution imaging is needed. To overcome this limitation, the current work developed a novel view-sharing data analysis scheme suitable for dynamic cardiac PET imaging using 18F-NaF as the tracer and tracer kinetic model analysis. This scheme was tested in a rat model of cardiovascular function where the relationship between direct transonic flow measures of cardiac output were highly correlated (f(x) = 1.0216x − 24.233, R = 0.9158, p < 0.001) with the new model. Similarly, derived measures of stroke volume were also highly correlated (f(x) = 0.9655x − 0.0428, R = 0.9453, p < 0.001) with the current approach. Administration of xylazine caused a statistically significant increase in stroke volume (0.32 ± 0.07 ml, p = 0.003, n = 4) and a significant decrease in both heart rate (−155 ± 7.1 beats/min, p < 0.001, n = 4) and cardiac output (−75.9 ± 23.0 ml/kg min, p = 0.01, n = 4). These findings suggest that the new sinogram binning and kinetic modeling methods produce reliable cardiac function measures suitable for longitudinal monitoring of cardiovascular function.

Multimodality calibration for simultaneous fluoroscopic and nuclear imaging.

Abstract: Background Simultaneous real-time fluoroscopic and nuclear imaging could benefit image-guided (oncological) procedures. To this end, a hybrid modality is currently being developed by our group, by combining a c-arm with a gamma camera and a four-pinhole collimator. Accurate determination of the system parameters that describe the position of the x-ray tube, x-ray detector, gamma camera, and collimators is crucial to optimize image quality. The purpose of this study was to develop a calibration method that estimates the system parameters used for reconstruction. A multimodality phantom consisting of five point sources was created. First, nuclear and fluoroscopic images of the phantom were acquired at several distances from the image intensifier. The system parameters were acquired using physical measurement, and multimodality images of the phantom were reconstructed. The resolution and co-registration error of the point sources were determined as a measure of image quality. Next, the system parameters were estimated using a calibration method, which adjusted the parameters in the reconstruction algorithm, until the resolution and co-registration were optimized. For evaluation, multimodality images of a second set of phantom acquisitions were reconstructed using calibrated parameter sets. Subsequently, the resolution and co-registration error of the point sources were determined as a measure of image quality. This procedure was performed five times for different noise simulations. In addition, simultaneously acquired fluoroscopic and nuclear images of two moving syringes were obtained with parameter sets from before and after calibration.

Lesion quantification and detection in myocardial (18)F-FDG PET using edge-preserving priors and anatomical information from CT and MRI: a simulation study.

Abstract: The limited spatial resolution of the clinical PET scanners results in image blurring and does not allow for accurate quantification of very thin or small structures (known as partial volume effect). In cardiac imaging, clinically relevant questions, e.g. to accurately define the extent or the residual metabolic activity of scarred myocardial tissue, could benefit from partial volume correction (PVC) techniques. The use of high-resolution anatomical information for improved reconstruction of the PET datasets has been successfully applied in other anatomical regions. However, several concerns linked to the use of any kind of anatomical information for PVC on cardiac datasets arise. The moving nature of the heart, coupled with the possibly non-simultaneous acquisition of the anatomical and the activity datasets, is likely to introduce discrepancies between the PET and the anatomical image, that in turn might mislead lesion quantification and detection. Non-anatomical (edge-preserving) priors could represent a viable alternative for PVC in this case. In this work, we investigate and compare the regularizing effect of different anatomical and non-anatomical priors applied during maximum-a-posteriori (MAP) reconstruction of cardiac PET datasets. The focus of this paper is on accurate quantification and lesion detection in myocardial 18F-FDG PET. Simulated datasets, obtained with the XCAT software, are reconstructed with different algorithms and are quantitatively analysed. The results of this simulation study show a superiority of the anatomical prior when an ideal, perfectly matching anatomy is used. The anatomical information must clearly differentiate between normal and scarred myocardial tissue for the PVC to be successful. In case of mismatched or missing anatomical information, the quality of the anatomy-based MAP reconstructions decreases, affecting both overall image quality and lesion quantification. The edge-preserving priors produce reconstructions with good noise properties and recovery of activity, with the advantage of not relying on an external, additional scan for anatomy. The performance of edge-preserving priors is acceptable but inferior to those of a well-applied anatomical prior that differentiates between lesion and normal tissue, in the detection and quantification of a lesion in the reconstructed images. When considering bull’s eye plots, all of the tested MAP algorithms produced comparable results.

An automatic delineation method for bone marrow absorbed dose estimation in (89)Zr PET/CT studies.

Abstract: The study aims to develop and validate an automatic delineation method for estimating red bone marrow (RM) activity concentration and absorbed dose in 89Zr positron emission tomography/computed tomography (PET/CT) studies. Five patients with advanced colorectal cancer received 37.1 ± 0.9 MBq [89Zr] cetuximab within 2 h after administration of a therapeutic dose of 500 mg m−2 unlabelled cetuximab. Per patient, five PET/CT scans were acquired on a Gemini TF-64 PET/CT scanner at 1, 24, 48, 96 and 144 h post injection. Low dose CT data were used to manually generate volumes of interest (VOI) in the lumbar vertebrae (LV). In addition, LV VOI were generated automatically using an active contour method in a low dose CT. RM activity was then determined by mapping the low dose CT-derived RM VOI onto the corresponding PET scans. Finally, these activities were used to derive residence times and, subsequently, the self and total RM absorbed doses using OLINDA/EXM 1.1. High correlations (r 2 > 0.85) between manual and automated VOI methods were obtained for both RM activity concentrations and total absorbed doses. On average, the automatic method provided values that were lower than 5 % compared to the manual method. An automated and efficient VOI method, based on an active contour approach, was developed, enabling accurate estimates of RM activity concentrations and total absorbed doses.

Estimation of activity of administered 18 F-fluorodeoxyglucose by measurement of the dose equivalent rate on the right temporal region of the head

Abstract: Positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) is now a routine procedure for the management of cancer patients. Intravenous administration of FDG is sometimes halted due to troubles. In such cases, estimations of the FDG dosage injected prior to halting administration may be helpful. We have established a method of estimating the activity of FDG to patients on the basis of the dose equivalent rate on the surface of the right temporal region of the head. The correlation of actual administered dosage with independent variables, such as the dose equivalent rate on the right temporal region of the head, age, sex, and body weight, was analyzed using multiple regression analysis to obtain linear, quadratic, and cubic regression equations. When entering independent variables, the cubic regression equation could be used to estimate an administered dosage with an accuracy of ±10 % for 62 % of all patients and ±20 % for 90 % of all patients. We conclude that this method is useful for estimating the administered dosage from the dose equivalent rate on the temporal region of the head.

A robust conversion method of radioactivities between plastic and NaI scintillation well counters for long-term quality control and quality assurance.

Abstract: Purpose The purpose of this study is to specify a simple procedure for a robust data conversion of radioactivity value between plastic scintillator (PL) and NaI scintillator (NaI) devices.