EARL compliance measurements on the biograph vision Quadra PET/CT system with a long axial field of view.

BACKGROUND: Our aim was to determine sets of reconstruction parameters for the Biograph Vision Quadra (Siemens Healthineers) PET/CT system that result in quantitative images compliant with the European Association of Nuclear Medicine Research Ltd. (EARL) criteria. Using the Biograph Vision 600 (Siemens Healthineers) PET/CT technology but extending the axial field of view to 106 cm, gives the Vision Quadra currently an around fivefold higher sensitivity over the Vision 600 with otherwise comparable spatial resolution. Therefore, we also investigated how the number of incident positron decays-i.e., exposure-affects EARL compliance. This will allow estimating a minimal acquisition time or a minimal applied dose in clinical scans while retaining data comparability. METHODS: We measured activity recovery curves on a NEMA IEC body phantom filled with an aqueous 18F solution and a sphere to background ratio of 10-1 according to the latest EARL guidelines. Reconstructing 3570 image sets with varying OSEM PSF iterations, post-reconstruction Gaussian filter full width at half maximum (FWHM), and varying exposure from 59 kDecays/ml (= 3 s frame duration) to 59.2 MDecays/ml (= 1 h), allowed us to determine sets of parameters to achieve compliance with the current EARL 1 and EARL 2 standards. Recovery coefficients (RCs) were calculated for the metrics RCmax, RCmean, and RCpeak, and the respective recovery curves were analyzed for monotonicity. The background's coefficient of variation (COV) was also calculated. RESULTS: Using 6 iterations, 5 subsets and 7.8 mm Gauss filtering resulted in optimal EARL1 compliance and recovery curve monotonicity in all analyzed frames, except in the 3 s frames. Most robust EARL2 compliance and monotonicity were achieved with 2 iterations, 5 subsets, and 3.6 mm Gauss FWHM in frames with durations between 30 s and 10 min. RCpeak only impeded EARL2 compliance in the 10 s and 3 s frames. CONCLUSIONS: While EARL1 compliance was robust over most exposure ranges, EARL2 compliance required exposures between 1.2 MDecays/ml to 11.5 MDecays/ml. The Biograph Vision Quadra's high sensitivity makes frames as short as 10 s feasible for comparable quantitative images. Lowering EARL2 RCmax limits closer to unity would possibly even permit shorter frames.

Towards guidelines to harmonize textural features in PET: Haralick textural features vary with image noise, but exposure-invariant domains enable comparable PET radiomics.

PURPOSE: Image texture is increasingly used to discriminate tissues and lesions in PET/CT. For quantification or in computer-aided diagnosis, textural feature analysis must produce robust and comparable values. Because statistical feature values depend on image count statistics, we investigated in depth the stability of Haralick features values as functions of acquisition duration, and for common image resolutions and reconstructions. METHODS: A homogeneous cylindrical phantom containing 9.6 kBq/ml Ge-68 was repeatedly imaged on a Siemens Biograph mCT, with acquisition durations ranging from three seconds to three hours. Images with 1.5, 2, and 4 mm isometrically spaced voxels were reconstructed with filtered back-projection (FBP), ordered subset expectation maximization (OSEM), and the Siemens TrueX algorithm. We analysed Haralick features derived from differently quantized (3 to 8-bit) grey level co-occurrence matrices (GLCMs) as functions of exposure E, which we defined as the product of activity concentration in a volume of interest (VOI) and acquisition duration. The VOI was a 50 mm wide cube at the centre of the phantom. Feature stability was defined for df/dE → 0. RESULTS: The most stable feature values occurred in low resolution FBPs, whereas some feature values from 1.5 mm TrueX reconstructions ranged over two orders of magnitude. Within the same reconstructions, most feature value-exposure curves reached stable plateaus at similar exposures, regardless of GLCM quantization. With 8-bit GLCM, median time to stability was 16 s and 22 s for FBPs, 18 s and 125 s for OSEM, and 23 s, 45 s, and 76 s for PSF reconstructions, with longer durations for higher resolutions. Stable exposures coincided in OSEM and TrueX reconstructions with image noise distributions converging to a Gaussian. In FBP, the occurrence of stable values coincided the disappearance of negatives image values in the VOI. CONCLUSIONS: Haralick feature values depend strongly on exposure, but invariance exists within defined domains of exposure. Here, we present an easily replicable procedure to identify said stable exposure domains, where image noise does not substantially add to textural feature values. Only by imaging at predetermined feature-invariant exposure levels and by adjusting exposure to expected activity concentrations, can textural features have a quantitative use in PET/CT. The necessary exposure levels are attainable by modern PET/CT systems in clinical routine.

Digital versus analogue PET in [68Ga]Ga-PSMA-11 PET/CT for recurrent prostate cancer: a matched-pair comparison.

PURPOSE: Digital PET/CT scanners represent a significant step forward in molecular imaging. We report here the clinical impact of digital PET in PSMA-PET/CT. METHODS: In this retrospective study, 88 consecutive patients who underwent [68Ga]Ga-PSMA-11 PET/CT on a digital PET/CT (dPET/CT) scanner for recurrent prostate cancer (PC) were included in a first cohort. In a second step, 88 individuals who underwent an analogue [68Ga]Ga-PSMA-11 PET/CT (aPET/CT) were selected after they were matched to the first cohort for clinical parameters. Following consensus read by two nuclear medicine physicians, the number and type of PC lesions as well as benign, PSMA-positive lesions were recorded. The results were complemented by extensive [68Ga]Ga phantom measurements to determine imaging characteristics of both scanners. RESULTS: dPET/CT revealed a greater number of PC lesions compared to aPET/CT (326 versus 142) as well as a proportional increase in benign causes of tracer-uptake (144 versus 65). A greater number of scans were noted as pathological for PC on dPET/CT (74/88) compared to aPET/CT (64/88, p < 0.05). The PSMA positivity rate for PC was significantly higher in dPET/CT for the lowest PSA values (PSA < 2.0 ng/ml, p < 0.05). CONCLUSION: dPET/CT detected more PC lesions compared to aPET/CT. A significantly higher rate of pathological PET/CTs was noted in the group with the lowest PSA values. A higher number of benign PSMA-positive lesions were also noted in dPET/CT. The differences could be plausibly explained by the measured imaging characteristics of the scanners.

Technical Note: Transconvolution based equalization of positron energy effects for the use of 68 Ge/68 Ga phantoms in determining 18 F PET recovery.

PURPOSE: Avoiding measurement variability from 18 F phantom preparation by using 68 Ge/68 Ga phantoms for the determination of 18 F recovery curves (RC) in clinical quality assurance measurements and for PET/CT site qualification in multicentre clinical trials. METHODS: RCs were obtained from PET/CT measurements of seven differently sized phantom spheres filled either with 18 F or with 68 Ga. RCs for the respective other isotope were then determined by two different methods: In the first method, images were convolved with positron range transconvolution functions derived from positron annihilation distributions found in literature. This method generated recasted images matching images using the respective other isotope. In the second method, the PET/CT system's isotope independent (intrinsic) point spread function was determined from said phantom measurements and convolved with numerical representations simulating hot spheres filled with the respective other isotope. These simulations included the isotope specific positron annihilation distributions. Recovered activity concentrations were compared between recasted images, simulated images, and the originally acquired images. RESULTS: 18 F and 68 Ga recovery was successfully determined from image acquisitions of the respective opposite isotope as well as from the simulations. 68 Ga RCs derived from 18 F data had a normalized root-mean-square deviation (NRMSD) from real 68 Ga measurements of 0.019% when using the first method and of 0.008% when using the second method. 18 F RCs derived from 68 Ga data had a NRMSD from real 18 F measurements of 0.036% when using the first method and of 0.038% when using the second method. CONCLUSIONS: Applying the principles of transconvolution, 18 F RCs can be recalculated from 68 Ga phantom measurements with excellent accuracy. The maximal additionally introduced error was below 0.4% of the error currently accepted for RCs in the site qualification of multicentre clinical trials by the EARL program of the European Association of Nuclear Medicine (EANM). Therefore, our methods legitimately allow for the use of long-lived solid state 68 Ge/68 Ga phantoms instead of manually prepared 18 F phantoms to characterize comparability of 18 F measurements across different imaging sites or of longitudinal 18 F measurements at a single PET/CT system.

T2-relaxometry predicts outcome of DBS in idiopathic Parkinson's disease.

INTRODUCTION: Deep brain stimulation (DBS) nowadays is a well-established treatment of motor symptoms in Parkinson's disease. The subthalamic nucleus (STN) is a common target for DBS, because motor improvements have been shown to be superior to best medical therapy, if DBS electrodes have been appropriately positioned. DBS target identification can be assisted by MRI beyond structural imaging by spatially resolved measurement of T2-relaxation times (T2r). AIM: We pose the question, whether T2r of the STN is linked to the severity of the disease and whether outcome of DBS may be correlated to an asymmetric manifestation of the disease. Further, we investigated if abnormal T2r in the STN may be predictive for outcome of DBS. METHODS: Twelve patients underwent preoperative MR imaging including a multi echo relaxometry sequence (3 Tesla, Siemens Medical Systems, Erlangen, Germany) ahead of DBS. T2r were determined for STN, substantia nigra (SN), red nucleus (RN) and centrum semiovale (CSO). Unified Parkinson's disease Rating Scale (UPDRS) scores were tested before and after DBS. Patients' T2r and deduced values representing left-right asymmetry of measurements were correlated with UPDRS scores and measures for outcome of DBS. Furthermore, patients' T2r were compared with T2r measurements in 12 healthy controls (HC). RESULTS: Patients' T2r for SN (mean 45.4 ms ± 4.4 ms) and STN (mean 56.4 ms ± 3.8 ms) were significantly shorter than T2r in HCs for SN (mean 60.7 ± 4.6) and STN (mean 66.1 ms ± 4.0 ms). While no mean T2r asymmetry was found in the SN, patients' mean T2r for STN showed a weakened left-right correlation (Pearson correlation coefficient 0.19 versus 0.72 in HC) indicating asymmetric degeneration. T2r asymmetry was not linked to the more severely affected hemisphere. The respective lower T2r within the left or right target region was significantly correlated to the outcome in terms of UPDRS III improvement in "off" state (Pearson correlation 0.82 corresponding to p â‰ª 0.01). Patients with T2r of STN lower than 50 ms showed no response to DBS in the UPDRS. The maximum T2r for SN correlated to the improvement between UPDRS "off" minus and "on" (Dopamine response) but failed to predict DBS outcome. CONCLUSIONS: The lower boundaries of T2r in the STN predict motor outcome in DBS. T2r asymmetry in the STN is not associated with increased clinical symptoms, but with response to therapy. Thus, patients with very low T2r may be inappropriate candidates for DBS.

Isotope independent determination of PET/CT modulation transfer functions from phantom measurements on spheres.

PURPOSE: A PET/CT system's imaging capabilities are best described by its point spread function (PSF) in the spatial domain or equivalently by its modulation transfer function (MTF) in the spatial frequency domain. Knowing PSFs or MTFs is a prerequisite for many numerical methods attempting to improve resolution and to reduce the partial volume effect. In PET/CT, the observed PSF is a convolution of the system's intrinsic imaging capabilities including image reconstruction (PSF0) and the positron range function (PRF) of the imaged ß+ emitting isotope. A PRF describes the non-Gaussian distribution of ß+ annihilation events around a hypothetical point source. The main aim was to introduce a new method for determining a PET/CT system's intrinsic MTF (MTF0) from phantom measurements of hot spheres independently of the ß+ emitting isotope used for image acquisition. Secondary aim was to examine non-Gaussian and nonlinear MTFs of a modern iterative reconstruction algorithm. METHODS: PET/CT images of seven phantom spheres with volumes ranging from 0.25 to 16 ml and filled either with 18F or with 68Ga were acquired and reconstructed using filtered back projection (FBP). MTFs were modeled with linear splines. The spline fit iteratively minimized the mean squared error between the acquired PET/CT image and a convolution of the thereof derived PSF with a numerical representation of the imaged hot phantom sphere. For determining MTF0, the numerical sphere representations were convolved with a PRF, simulating a fill with either 18F or 68Ga. The MTFs determined by this so-called MTF fit method were compared with MTFs derived from point source measurements and also compared with MTFs derived with a previously published PSF fit method. The MTF fit method was additionally applied to images reconstructed by a vendor iterative algorithm with PSF recovery (Siemens TrueX). RESULTS: The MTF fit method was able to determine 18F and 68Ga dependent MTFs and MTF0 from FBP reconstructed images. Root-mean-square deviation between fit determined MTFs and point source determined MTFs ranged from 0.023 to 0.039. MTFs from Siemens TrueX reconstructions varied with size of the imaged sphere. CONCLUSIONS: MTF0 can be determined regardless of the imaged isotope, when using existing PRF models for the MTF fit method presented. The method proves that modern iterative PET/CT reconstruction algorithms have nonlinear imaging properties. This behaviour is not accessible by point source measurements. MTFs resulting from these clinically applied algorithms need to be estimated from objects of similar geometry to those intended for clinical imaging.

Transconvolution and the virtual positron emission tomograph--a new method for cross calibration in quantitative PET∕CT imaging.

PURPOSE: Positron emission tomography (PET)∕computed tomography (CT) measurements on small lesions are impaired by the partial volume effect, which is intrinsically tied to the point spread function of the actual imaging system, including the reconstruction algorithms. The variability resulting from different point spread functions hinders the assessment of quantitative measurements in clinical routine and especially degrades comparability within multicenter trials. To improve quantitative comparability there is a need for methods to match different PET∕CT systems through elimination of this systemic variability. Consequently, a new method was developed and tested that transforms the image of an object as produced by one tomograph to another image of the same object as it would have been seen by a different tomograph. The proposed new method, termed Transconvolution, compensates for differing imaging properties of different tomographs and particularly aims at quantitative comparability of PET∕CT in the context of multicenter trials. METHODS: To solve the problem of image normalization, the theory of Transconvolution was mathematically established together with new methods to handle point spread functions of different PET∕CT systems. Knowing the point spread functions of two different imaging systems allows determining a Transconvolution function to convert one image into the other. This function is calculated by convolving one point spread function with the inverse of the other point spread function which, when adhering to certain boundary conditions such as the use of linear acquisition and image reconstruction methods, is a numerically accessible operation. For reliable measurement of such point spread functions characterizing different PET∕CT systems, a dedicated solid-state phantom incorporating (68)Ge∕(68)Ga filled spheres was developed. To iteratively determine and represent such point spread functions, exponential density functions in combination with a Gaussian distribution were introduced. Furthermore, simulation of a virtual PET system provided a standard imaging system with clearly defined properties to which the real PET systems were to be matched. A Hann window served as the modulation transfer function for the virtual PET. The Hann's apodization properties suppressed high spatial frequencies above a certain critical frequency, thereby fulfilling the above-mentioned boundary conditions. The determined point spread functions were subsequently used by the novel Transconvolution algorithm to match different PET∕CT systems onto the virtual PET system. Finally, the theoretically elaborated Transconvolution method was validated transforming phantom images acquired on two different PET systems to nearly identical data sets, as they would be imaged by the virtual PET system. RESULTS: The proposed Transconvolution method matched different PET∕CT-systems for an improved and reproducible determination of a normalized activity concentration. The highest difference in measured activity concentration between the two different PET systems of 18.2% was found in spheres of 2 ml volume. Transconvolution reduced this difference down to 1.6%. In addition to reestablishing comparability the new method with its parameterization of point spread functions allowed a full characterization of imaging properties of the examined tomographs. CONCLUSIONS: By matching different tomographs to a virtual standardized imaging system, Transconvolution opens a new comprehensive method for cross calibration in quantitative PET imaging. The use of a virtual PET system restores comparability between data sets from different PET systems by exerting a common, reproducible, and defined partial volume effect.

Metabolic pathway and distribution of superparamagnetic iron oxide nanoparticles: in vivo study.

BACKGROUND: Experimental tissue fusion benefits from the selective heating of superparamagnetic iron oxide nanoparticles (SPIONs) under high frequency irradiation. However, the metabolic pathways of SPIONs for tissue fusion remain unknown. Hence, the goal of this in vivo study was to analyze the distribution of SPIONs in different organs by means of magnetic resonance imaging (MRI) and histological analysis after a SPION-containing patch implantation. METHODS: SPION-containing patches were implanted in rats. Three animal groups were studied histologically over six months. Degradation assessment of the SPION-albumin patch was performed in vivo using MRI for iron content localization and biodistribution. RESULTS: No SPION degradation or accumulation into the reticuloendothelial system was detected by MRI, MRI relaxometry, or histology, outside the area of the implantation patch. Concentrations from 0.01 µg/mL to 25 µg/mL were found to be hyperintense in T1-like gradient echo sequences. The best differentiation of concentrations was found in T2 relaxometry, susceptibility-sensitive gradient echo sequences, and in high repetition time T2 images. Qualitative and semiquantitative visualization of small concentrations and accumulation of SPIONs by MRI are feasible. In histological liver samples, Kupffer cells were significantly correlated with postimplantation time, but no differences were observed between sham-treated and induction/no induction groups. Transmission electron microscopy showed local uptake of SPIONs in macrophages and cells of the reticuloendothelial system. Apoptosis staining using caspase showed no increased toxicity compared with sham-treated tissue. Implanted SPION patches were relatively inert with slow, progressive local degradation over the six-month period. No distant structural alterations in the studied tissue could be observed. CONCLUSION: Systemic bioavailability may play a role in specific SPION implant toxicity and therefore the local degradation process is a further aspect to be assessed in future studies.

A navigation system for percutaneous needle interventions based on PET/CT images: design, workflow and error analysis of soft tissue and bone punctures.

Percutaneous needle intervention based on PET/CT images is effective, but exposes the patient to unnecessary radiation due to the increased number of CT scans required. Computer assisted intervention can reduce the number of scans, but requires handling, matching and visualization of two different datasets. While one dataset is used for target definition according to metabolism, the other is used for instrument guidance according to anatomical structures. No navigation systems capable of handling such data and performing PET/CT image-based procedures while following clinically approved protocols for oncologic percutaneous interventions are available. The need for such systems is emphasized in scenarios where the target can be located in different types of tissue such as bone and soft tissue. These two tissues require different clinical protocols for puncturing and may therefore give rise to different problems during the navigated intervention. Studies comparing the performance of navigated needle interventions targeting lesions located in these two types of tissue are not often found in the literature. Hence, this paper presents an optical navigation system for percutaneous needle interventions based on PET/CT images. The system provides viewers for guiding the physician to the target with real-time visualization of PET/CT datasets, and is able to handle targets located in both bone and soft tissue. The navigation system and the required clinical workflow were designed taking into consideration clinical protocols and requirements, and the system is thus operable by a single person, even during transition to the sterile phase. Both the system and the workflow were evaluated in an initial set of experiments simulating 41 lesions (23 located in bone tissue and 18 in soft tissue) in swine cadavers. We also measured and decomposed the overall system error into distinct error sources, which allowed for the identification of particularities involved in the process as well as highlighting the differences between bone and soft tissue punctures. An overall average error of 4.23 mm and 3.07 mm for bone and soft tissue punctures, respectively, demonstrated the feasibility of using this system for such interventions. The proposed system workflow was shown to be effective in separating the preparation from the sterile phase, as well as in keeping the system manageable by a single operator. Among the distinct sources of error, the user error based on the system accuracy (defined as the distance from the planned target to the actual needle tip) appeared to be the most significant. Bone punctures showed higher user error, whereas soft tissue punctures showed higher tissue deformation error.

Multimodal target correction by local bone registration: a PET/CT evaluation.

PET/CT guidance for percutaneous interventions allows biopsy of suspicious metabolically active bone lesions even when no morphological correlation is delineable in the CT images. Clinical use of PET/CT guidance with conventional step-by-step technique is time consuming and complicated especially in cases in which the target lesion is not shown in the CT image. Our recently developed multimodal instrument guidance system (IGS) for PET/CT improved this situation. Nevertheless, bone biopsies even with IGS have a trade-off between precision and intervention duration which is proportional to patient and personnel exposure to radiation. As image acquisition and reconstruction of PET may take up to 10 minutes, preferably only one time consuming combined PET/CT acquisition should be needed during an intervention. In case of required additional control images in order to check for possible patient movements/deformations, or to verify the final needle position in the target, only fast CT acquisitions should be performed. However, for precise instrument guidance accounting for patient movement and/or deformation without having a control PET image, it is essential to be able to transfer the position of the target as identified in the original PET/CT to a changed situation as shown in the control CT.

PET/CT-guided biopsies of metabolically active bone lesions: applications and clinical impact.

PURPOSE: In a minority of cases a definite diagnosis and stage grouping in cancer patients is not possible based on the imaging information of PET/CT. We report our experience with percutaneous PET/CT-guided bone biopsies to histologically verify the aetiology of hypermetabolic bone lesions. METHODS: We retrospectively reviewed the data of 20 consecutive patients who underwent multimodal image-guided bone biopsies using a dedicated PET/CT system in a step-by-step technique. Technical and clinical success rates of PET/CT-guided biopsies were evaluated. Questionnaires were sent to the referring physicians to assess the impact of biopsies on patient management and to check the clinical need for PET/CT-guided biopsies. RESULTS: Clinical indications for biopsy were to histologically verify the aetiology of metabolically active bone lesions without a morphological correlate confirming the suspicion of metastases in 15 patients, to determine the origin of suspected metastases in 3 patients and to evaluate the appropriateness of targeted therapy options in 2 patients. Biopsies were technically successful in all patients. In 19 of 20 patients a definite histological diagnosis was possible. No complications or adverse effects occurred. The result of PET/CT-guided bone biopsies determined a change of the planned treatment in overall 56% of patients, with intramodality changes, e.g. chemotherapy with palliative instead of curative intent, and intermodality changes, e.g. systemic therapy instead of surgery, in 22 and 50%, respectively. CONCLUSION: PET/CT-guided bone biopsies are a promising alternative to conventional techniques to make metabolically active bone lesions-especially without a distinctive morphological correlate-accessible for histological verification. PET/CT-guided biopsies had a major clinical impact in patients who otherwise cannot be reliably stage grouped at the time of treatment decisions.