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Purpose: Recent technical advancements in PET imaging have improved sensitivity and spatial resolution. Consequently, clinical nuclear medicine will be confronted with PET images on a previously unfamiliar resolution. To better understand [18F]FDG distribution at submillimetric scale, a direct correlation of radionuclide-imaging and histopathology is required. Methods: A total of five patients diagnosed with a malignancy of the head and neck were injected with a clinical activity of [18F]FDG before undergoing surgical resection. The resected specimen was imaged using a preclinical high-resolution PET/CT, followed by slicing of the specimen. Multiple slices were rescanned using a micro-PET/CT device, and one of the slices was snap-frozen for frozen sections. Frozen sections were placed on an autoradiographic film, followed by haematoxylin and eosin staining to prepare them for histopathological assessment. The results from both autoradiography and histopathology were co-registered using an iterative co-registration algorithm, and regions of interest were identified to study radiotracer uptake. Results: The co-registration between the autoradiographs and their corresponding histopathology was successful in all specimens. The use of this novel methodology allowed direct comparison of autoradiography and histopathology and enabled the visualisation of uncharted heterogeneity in [18F]FDG uptake in both benign and malignant tissue. Conclusion: We here describe a novel methodology enabling the direct co-registration of [18F]FDG autoradiography with the gold standard of histopathology in human malignant tissue. The future use of the current methodology could further increase our understanding of the distribution of radionuclides in surgically excised malignancies and hence, improve the integration of pathology and molecular imaging in a multiscale perspective. Trial registration: ClinicalTrials.gov Identifier: NCT05068687 [ABSTRACT FROM AUTHOR]

Tomographic reconstruction from positron emission tomography (PET) data is an ill-posed problem that requires regularization. An attractive approach is to impose an l1 -regularization constraint, which favors sparse solutions in the wavelet domain. This can be achieved quite efficiently thanks to the iterative algorithm developed by Daubechies et al., 2004. In this paper, we apply this technique and extend it for the reconstruction of dynamic (spatio-temporal) PET data. Moreover, instead of using classical wavelets in the temporal dimension, we introduce exponential-spline wavelets (E-spline wavelets) that are specially tailored to model time activity curves (TACs) in PET. We show that the exponential-spline wavelets naturally arise from the compartmental description of the dynamics of the tracer distribution. We address the issue of the selection of the 'optimal' E-spline parameters (poles and zeros) and we investigate their effect on reconstruction quality. We demonstrate the usefulness of spatio-temporal regularization and the superior performance of E-spline wavelets over conventional Battle-Lemarie wavelets in a series of experiments: the 1-D fitting of TACs, and the tomographic reconstruction of both simulated and clinical data. We find that the E-spline wavelets outperform the conventional wavelets in terms of the reconstructed signal-to-noise ratio (SNR) and the sparsity of the wavelet coefficients. Based on our simulations, we conclude that replacing the conventional wavelets with E-spline wavelets leads to equal reconstruction quality for a 40% reduction of detected coincidences, meaning an improved image quality for the same number of counts or equivalently a reduced exposure to the patient for the same image quality. Index Terms--Differential system, E-spline wavelets, [l.sub.1]-regularization, spatio-temporal positron emission tomography (PET) reconstruction, time-activity-curves.

A maximum likelihood reconstruction algorithm for gated dynamic cardiac PET studies was developed and evaluated. A two dimensional tensor product spline basis spanning the time and gate domain is proposed. The activity variations introduced by the biochemical kinetics and cardiac motion are modeled as conic combinations of the B-spline basis functions. The basis explicitly takes the cyclic nature of the heart motion into account. We make use of the expectation-maximization (EM) algorithm to derive a closed form iteration scheme for the reconstruction. The proposed algorithm is validated through computer simulations of the dynamic NCAT beating heart phantom and the kinetics of [sup.13]N-ammonia uptake. We used the Monte Carlo simulator GATE to simulate a typical PET scanner. We qualitatively found that a reconstruction using cubic splines resulted in smoother images while better delineating the myocardial wall. Fourth order spline modeling reduced the mean squared error (MSE) of binned reconstruction by 56% whereas conventional Gaussian filtering reduced the MSE by 38%. Spline modeling in the gate domain reduced the MSE by 72 % compared to a reduction of 47 % obtained with filtering. Quantitative evaluation of the reconstructed motion information suggested that the number of basis functions in the gate domain could be reduced from 16 in a framed approach to 5 for reconstructions using a higher order spline interpolation. Index Terms--Dynamic and gated PET, myocardium, tensor product splines.

A theoretical formulation of the effective point spread function of a slat collimator on a strip detector has been derived. The used technique to obtain the geometric transfer function, which is the Fourier transform of the effective point source image, is based on the geometric characteristics of a single gap and it accurately describes the performance of the collimation system for system analysis. Valuable conclusions resulting from this geometric transfer function could be made on the sensitivity, on the spatial resolution, and on the line spread function of the imaging system. We found that the sensitivity was dependent on the angle of incidence and on the distance to the detector. The spatial resolution was constant in a plane at a fixed distance to the detector and closed analytical expressions were derived for transaxial line spread profiles. These results were confirmed by the appropriate Monte Carlo simulations. The presented formulation of the geometric transfer function will be useful with usage in iterative reconstruction algorithms to incorporate distance dependent effects. Index Terms--Effective point spread function, geometric transfer function, resolution, sensitivity, solstice.

Nonuniform patient attenuation maps can be acquired using an axially moving point source of a high energy isotope that emits a fanbeam of photons. We simulated the Beacon attenuation correction tool attached to multiheaded Single Photon Emission Computed Tomography (SPECT) cameras which uses this approach. We investigated the scatter order of the photons reaching the detector, and the scatter contributions from the different detector components were evaluated for different energy windows. In case of simultaneous emission and transmission scanning the spatial signals are electronically windowed to allow differentiation between photons from the attenuation and from the emission source. However, an additional correction needs to be applied for cross-contamination. When applying the Beacon device in hybrid mode [gammacamera-Positron Emission Tomography (PET)] there are no degrees of freedom for crystal and collimator. The inter-window contamination was thus examined in detail to derive possible protocol optimizations for that dedicated setup. For the case of applying Beacon-SPECT, we performed multiple types of simulations including different crystal thicknesses and different collimators to evaluate the inter-window contamination. The main conclusion of this work is that a thick crystal detector coupled to a Low Energy High Resolution (LEHR) collimator is the best solution for acquiring attenuation maps in low energy applications. For medium energy studies attenuation maps have to be rescaled to account for the low sensitivity near the center of the patient. Fully Monte Carlo simulating the system matrix for medium energy studies on low energy collimators in order to replace the Medium Energy General Purpose (MEGP) collimators by the LEHR variants appeared to be a more valuable approach. This last method is penalized by a computational burden but results in an improved image quality after reconstruction. Index Terms--Beacon, Geant4 Application for Tomographic Emission (GATE), transmission imaging.

The low coincidence fraction (ratio of true coincidences to single events detected) and a limited count rate capability reduce performance of hybrid PET systems as compared with dedicated PET. Axial collimation (i.e., using septa oriented perpendicular to the axis of rotation) has been used to reduce acceptance of photons from outside the field of view, reduce scattered events, and allow the use of 2-D image reconstruction algorithms. The major drawback of axial collimation is a reduced coincidence detection efficiency. The goal of this study was to evaluate the effect of axial collimator septal spacing, as well as to evaluate a new hybrid parallel-fan beam axial collimator design which may better shield out of field-of-view (FOV) photons, reduce the number of scattered events, and increase the sensitivity to the central FOV. The GEANT 3.21 Monte Carlo (MC) simulation code was modified to model a Philips IRIX triple-head hybrid PET system in the 0[degrees] - 90[degrees] - 270[degrees] geometry and used to investigate different axial collimator designs. Both lead and tungsten septa were investigated. Basic PET system parameters such as scatter fraction, global true coincidences to single events (T/S) ratio, axial profiles of the T/S ratio, and energy spectra were examined. Noise equivalent count (NEC) rate curves were plotted. Noise and contrast were evaluated for different collimator designs and reconstruction strategies. Comparisons to an experimentally acquired line source phantom showed that the GEANT 3.21 MC simulation code accurately modeled the Philips IRIX camera. The T/S ratio was observed to increase with increasing septal spacing from 0.77 to 2.27 cm and was approximately constant for larger septal spacing. Widening the septal spacing modified the T/S axial profiles making them more nonuniform with a strong peak toward the axial center of the FOV. Using the hybrid parallel-fan beam axial collimator provided a more uniform axial T/S profile for some septal spacings and improved contrast and decreased the noise in the reconstructed slices. In addition, for a given single events rate, a larger proportion of single events were measured within the photopeak energy window as septal spacing decreased. This observation can have implications on the recorded random rate for some PET systems. Index Terms--Monte Carlo simulation, positron emission tomography (PET), slat collimator.

In PET imaging with large area NaI scintillators, uncertainty in the measured position of a photon hitting the detector at an oblique angle exists due to the thickness of the crystal in the detector. To evaluate the influence of the crystal thickness and the angle of incidence on the spatial resolution, simulations, and measurements of a dual- and triple-headed PET system in different configurations were performed. In the simulations, the resolution was calculated as a function of: head radii, crystal thickness, head orientation, and the maximum angle of incidence. The influence of these parameters (except crystal thickness) was also evaluated by measurements on a dual-headed AXIS and an a triple-headed IRIX PET system. It was observed that reducing the average angle-of-incidence (and, hence, reducing the depth-of-interaction uncertainty) tended to improve the spatial resolution. This could be accomplished by restricting the maximum angle-of-incidence, increasing the separation of the heads or changing the orientation of the heads (a 0-120-240 configuration has a greater average angle-of-incidence than a 0-90-180 or 0-180 configuration). However, when taking the effect of noncolinearity of the annihilation into account, increasing the separation of the heads results in a degradation of resolution. The resolution improved by decreasing the crystal thickness (since depth-of-interaction uncertainty was reduced). The resolution was worst for all parameters expected to yield the highest sensitivity (a thick crystal, small radius, and a large acceptance angle). Index Terms--Camera, gamma, PET, resolution.

Accurate quantification of emission computed tomography data (PET-SPECT) is limited by partial volume effects. This paper compares two approaches, described in the literature, to measure accurately the true tissue tracer activity within a tissue compartment, defined by anatomical side information. The first approach is based on the selection of an appropriate number of regions. The second method is based on a minimum norm least square solution, taking into account the whole image. These methods assume a constant activity within one tissue compartment and have similar performance when this assumption is correct. We demonstrate the equivalence of both methodologies in the case of an appropriate region selection for the first technique. We also propose two new methods allowing activity fluctuations within the same anatomical tissue compartment. The first technique uses the minimum norm least square solution to estimate a higher number of activities within one tissue compartment while taking into account the whole reconstructed emission computed tomography image. The second method estimates the activity of a tissue compartment locally by linear regression analysis within a sliding window. A simple simulation study shows that these techniques yield a more accurate quantification in the case of a nonhomogeneous activity distribution within one tissue compartment. Index Terms--FBP-SPECT, partial volume correction.