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 incorporating68Ge/68Ga 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.
CX 546, an allosteric positive modulator of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid‐type ionotropic glutamate receptors (AMPARs), belongs to a drug class called ampakines. These ...compounds have been shown to enhance long‐term potentiation (LTP), a cellular model of learning and memory, and improve animal learning task performance, and have augmented cognition in neurodegenerative patients. However, the chronic effect of CX546 on synaptic structures has not been examined. The structure and integrity of dendritic spines are thought to play a role in learning and memory, and their abnormalities have been implicated in cognitive disorders. In addition, their structural plasticity has been shown to be important for cognitive function, such that dendritic spine remodeling has been proposed as the morphological correlate for LTP. Here, we tested the effect of CX546 on dendritic spine remodeling following long‐term treatment. We found that, with prolonged CX546 treatment, organotypic hippocampal slice cultures showed a significant reduction in CA3–CA1 excitatory synapse and spine density. Electrophysiological approaches revealed that the CA3–CA1 circuitry compensates for this synapse loss by increasing synaptic efficacy through enhancement of presynaptic release probability. CX546‐treated slices showed prolonged and enhanced potentiation upon LTP induction. Furthermore, structural plasticity, namely spine head enlargement, was also more pronounced after CX546 treatment. Our results suggest a concordance of functional and structural changes that is enhanced with prolonged CX546 exposure. Thus, the improved cognitive ability of patients receiving ampakine treatment may result from the priming of synapses through increases in the structural plasticity and functional reliability of hippocampal synapses.
Here, we report that chronic treatment with the ampakine, CX546, results in the loss of excitatory synapses and dendritic spines in CA1 pyramidal neurons of the hippocampus. At the same time, chronic CX546 treatment enhances presynaptic release probability and both structural and functional plasticity following LTP induction. Our findings suggest that neurons are conditioned by ampakine to be more responsive to learning paradigms; thus improving cognitive functions.
Brain trauma can disrupt synaptic connections, and this in turn can prompt axons to sprout and form new connections. If these new axonal connections are aberrant, hyperexcitability can result. It has ...been shown that ablating tropomyosin‐related kinase B (TrkB), a receptor for brain‐derived neurotrophic factor (BDNF), can reduce axonal sprouting after hippocampal injury. However, it is unknown whether inhibiting BDNF‐mediated axonal sprouting will reduce hyperexcitability. Given this, our purpose here was to determine whether pharmacologically blocking BDNF inhibits hyperexcitability after injury‐induced axonal sprouting in the hippocampus. To induce injury, we made Schaffer collateral lesions in organotypic hippocampal slice cultures. As reported by others, we observed a 50% reduction in axonal sprouting in cultures treated with a BDNF blocker (TrkB‐Fc) 14 days after injury. Furthermore, lesioned cultures treated with TrkB‐Fc were less hyperexcitable than lesioned untreated cultures. Using electrophysiology, we observed a two‐fold decrease in the number of CA3 neurons that showed bursting responses after lesion with TrkB‐Fc treatment, whereas we found no change in intrinsic neuronal firing properties. Finally, evoked field excitatory postsynaptic potential recordings indicated an increase in network activity within area CA3 after lesion, which was prevented with chronic TrkB‐Fc treatment. Taken together, our results demonstrate that blocking BDNF attenuates injury‐induced hyperexcitability of hippocampal CA3 neurons. Axonal sprouting has been found in patients with post‐traumatic epilepsy. Therefore, our data suggest that blocking the BDNF–TrkB signaling cascade shortly after injury may be a potential therapeutic target for the treatment of post‐traumatic epilepsy.
Here, we report that following Schaffer collateral lesion, Brain‐Derived Neurotrophic Factor (BDNF) release can lead to axonal sprouting and hyperexcitability of area CA3 pyramidal neurons. Moreover, using patch‐clamp and field EPSP recordings we show that this hyperexcitability is not due to changes in intrinsic electrical properties of CA3 pyramidal neurons, but rather through BDNF‐dependent synapse formation.
The physical properties of yttrium-90 (
Y) allow for imaging with positron emission tomography/computed tomography (PET/CT). The increased sensitivity of long axial field-of-view (LAFOV) PET/CT ...scanners possibly allows to overcome the small branching ratio for positron production from
Y decays and to improve for the post-treatment dosimetry of
Y of selective internal radiation therapy.
For the challenging case of an image quality body phantom, we compare a full Monte Carlo (MC) dose calculation with the results from the two commercial software packages Simplicit90Y and Hermes. The voxel dosimetry module of Hermes relies on the
Y images taken with a LAFOV PET/CT, while the MC and Simplicit90Y dose calculations are image independent.
The resulting doses from the MC calculation and Simplicit90Y agree well within the error margins. The image-based dose calculation with Hermes, however, consistently underestimates the dose. This is due to the mismatch of the activity distribution in the PET images and the size of the volume of interest. We found that only for the smallest phantom sphere there is a statistically significant dependence of the Hermes dose on the image reconstruction parameters and scan time.
Our study shows that Simplicit90Y's local deposition model can provide a reliable dose estimate. On the other hand, the image based dose calculation suffers from the suboptimal reconstruction of the
Y distribution in small structures.
We aimed to print a solid-state germanium-68 phantom for positron emission tomography (PET) with excellent control of the activity concentration in the phantom material, with safe handling ...characteristics, and without inactive walls. To this end, we developed a novel method for incorporating germanium-68 into hydrophobic stereo-lithography monomers. The spontaneous phase transfer process provides complexation and induces phase transfer of aqueous ionic germanium-68 into the hydrophobic monomers, ensures homogenous isotope distribution in the rigid polymer matrix, and prevents leaching in aqueous environments. With this method, we additively manufactured radioactive spheres following the International Electrotechnical Commission design with the addition of a small sphere of 7.7 mm diameter. Extended leaching testing demonstrated near perfect source tightness. The same phantom can be repeatedly used in the quality management of multicenter clinical trials, without preparative errors. Long-lived solid-state phantoms produced with this method will provide consistent and reproducible validation of total body PET/CT systems. PET images with these phantoms acquired within a decaying gallium-68 background at different signal to background ratios showed homogenous activity distribution and no fill-related artefacts. The varying background allowed the assessment of trial specific acquisition protocols that match a given clinical question much better than todays predefined standard protocol.
Purpose
Avoiding measurement variability from 18F phantom preparation by using 68Ge/68Ga phantoms for the determination of 18F 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 18F or with 68Ga. 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
18F and 68Ga recovery was successfully determined from image acquisitions of the respective opposite isotope as well as from the simulations. 68Ga RCs derived from 18F data had a normalized root‐mean‐square deviation (NRMSD) from real 68Ga measurements of 0.019% when using the first method and of 0.008% when using the second method. 18F RCs derived from 68Ga data had a NRMSD from real 18F measurements of 0.036% when using the first method and of 0.038% when using the second method.
Conclusions
Applying the principles of transconvolution, 18F RCs can be recalculated from 68Ga 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 68Ge/68Ga phantoms instead of manually prepared 18F phantoms to characterize comparability of 18F measurements across different imaging sites or of longitudinal 18F measurements at a single PET/CT system.
Purpose
To investigate the performance of the new long axial field-of-view (LAFOV) Biograph Vision Quadra PET/CT and a standard axial field-of-view (SAFOV) Biograph Vision 600 PET/CT (both: Siemens ...Healthineers) system using an intra-patient comparison.
Methods
Forty-four patients undergoing routine oncological PET/CT were prospectively included and underwent a same-day dual-scanning protocol following a single administration of either
18
F-FDG (
n
= 20),
18
F-PSMA-1007 (
n
= 16) or
68
Ga-DOTA-TOC (
n
= 8). Half the patients first received a clinically routine examination on the SAFOV (FOV
axial
26.3 cm) in continuous bed motion and then immediately afterwards on the LAFOV system (10-min acquisition in list mode, FOV
axial
106 cm); the second half underwent scanning in the reverse order. Comparisons between the LAFOV at different emulated scan times (by rebinning list mode data) and the SAFOV were made for target lesion integral activity, signal to noise (SNR), target lesion to background ratio (TBR) and visual image quality.
Results
Equivalent target lesion integral activity to the SAFOV acquisitions (16-min duration for a 106 cm FOV) were obtained on the LAFOV in 1.63 ± 0.19 min (mean ± standard error). Equivalent SNR was obtained by 1.82 ± 1.00 min LAFOV acquisitions. No statistically significant differences (
p
> 0.05) in TBR were observed even for 0.5 min LAFOV examinations. Subjective image quality rated by two physicians confirmed the 10 min LAFOV to be of the highest quality, with equivalence between the LAFOV and the SAFOV at 1.8 ± 0.85 min. By analogy, if the LAFOV scans were maintained at 10 min, proportional reductions in applied radiopharmaceutical could obtain equivalent lesion integral activity for activities under 40 MBq and equivalent doses for the PET component of <1 mSv.
Conclusion
Improved image quality, lesion quantification and SNR resulting from higher sensitivity were demonstrated for an LAFOV system in a head-to-head comparison under clinical conditions. The LAFOV system could deliver images of comparable quality and lesion quantification in under 2 min, compared to routine SAFOV acquisition (16 min for equivalent FOV coverage). Alternatively, the LAFOV system could allow for low-dose examination protocols. Shorter LAFOV acquisitions (0.5 min), while of lower visual quality and SNR, were of adequate quality with respect to target lesion identification, suggesting that ultra-fast or low-dose acquisitions can be acceptable in selected settings.
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.
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.
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.
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.
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