Delocalized nonlinear vibrational modes and discrete breathers in ß-FPUT simple cubic lattice.

The problem of finding various discrete breathers (DBs) in the ß-Fermi-Pasta-Ulam-Tsingou simple cubic lattice is addressed. DBs are obtained by imposing localizing functions on delocalized nonlinear vibrational modes (DNVMs) having frequencies above the phonon spectrum of the lattice. Among 27 DNVMs with the wave vector at the boundary of the first Brillouin zone there are three satisfying this condition. Seven robust DBs of different symmetries are found using this approach.

Donanemab (LY3002813) Phase 1b Study in Alzheimer's Disease: Rapid and Sustained Reduction of Brain Amyloid Measured by Florbetapir F18 Imaging.

BACKGROUND: Donanemab (LY3002813) is an IgG1 antibody directed at an N­terminal pyroglutamate of amyloid beta epitope that is present only in brain amyloid plaques. OBJECTIVES: To assess effects of donanemab on brain amyloid plaque load after single and multiple intravenous doses, as well as pharmacokinetics, safety/tolerability, and immunogenicity. DESIGN: Phase 1b, investigator- and patient-blind, randomized, placebo-controlled study. SETTING: Patients recruited at clinical research sites in the United States and Japan. PARTICIPANTS: 61 amyloid plaque-positive patients with mild cognitive impairment due to Alzheimer's disease and mild-to-moderate Alzheimer's disease dementia. INTERVENTION: Six cohorts were dosed with donanemab: single dose 10-, 20- or 40- mg/kg (N = 18), multiple doses of 10-mg/kg every 2 weeks for 24 weeks (N = 10), and 10- or 20-mg/kg every 4 weeks for 72 weeks (N=18) or placebo (N = 15). MEASUREMENTS: Brain amyloid plaque load, using florbetapir positron emission tomography, was assessed up to 72 weeks. Safety was evaluated by occurrence of adverse events, magnetic resonance imaging, electrocardiogram, vital signs, laboratory testing, neurological monitoring, and immunogenicity. RESULTS: Treatment with donanemab resulted in rapid reduction of amyloid, even after a single dose. By 24 weeks, amyloid positron emission tomography mean changes from baseline for single donanemab doses in Centiloids were: -16.5 (standard error 11.22) 10-mg/kg intravenous; 40.0 (standard error 11.23) 20 mg/kg intravenous; and -49.6 (standard error 15.10) 40-mg/kg intravenous. Mean reduction of amyloid plaque in multiple dose cohorts by 24 weeks in Centiloids were: 55.8 (standard error 9.51) 10-mg/kg every 2 weeks; -50.2 (standard error 10.54) 10-mg/kg every 4 weeks; and -58.4 (standard error 9.66) 20-mg/kg every 4 weeks. Amyloid on average remained below baseline levels up to 72 weeks after a single dose of donanemab. Repeated dosing resulted in continued florbetapir positron emission tomography reductions over time compared to single dosing with 6 out of 28 patients attaining complete amyloid clearance within 24 weeks. Within these, 5 out of 10 patients in the 20 mg/kg every 4 weeks cohort attained complete amyloid clearance within 36 weeks. When dosing with donanemab was stopped after 24 weeks of repeat dosing in the 10 mg every 2 weeks cohort, florbetapir positron emission tomography reductions were sustained up to 72 weeks. For the single dose cohorts on day 1, dose proportional increases in donanemab pharmacokinetics were observed from 10 to 40 mg/kg. Dose proportional increases in pharmacokinetics were also observed at steady state with the multiple dose cohorts. Donanemab clearance was comparable across the dose levels. Mean donanemab elimination-half-life following 20 mg/kg single dose was 9.3 days with range of 5.6 to 16.2 days. Greater than 90% of patients had positive treatment-emergent antidrug antibodies with donanemab. However, overall, the treatment-emergent antidrug antibodies did not have a significant impact on pharmacokinetics. Donanemab was generally well tolerated. Amongst the 46 participants treated with donanemab, the following amyloid-related imaging abnormalities, common to the drug class, were observed: 12 vasogenic cerebral edema events (12 [19.7%] patients), 10 cerebral microhemorrhage events (6 [13.0%] patients), and 2 superficial siderosis events (2 [4.3%] patients). CONCLUSIONS: Single and multiple doses of donanemab demonstrated a rapid, robust, and sustained reduction up to 72 weeks in brain amyloid plaque despite treatment-emergent antidrug antibodies detected in most patients. Amyloid-related imaging abnormalities were the most common treatment-emergent event.

Nonlinear normal mode interactions in the SF(6) molecule studied with the aid of density functional theory.

Some exact interactions between vibrational modes in systems with discrete symmetry can be described by the theory of the bushes of nonlinear normal modes (NNMs) [G. M. Chechin and V. P. Sakhnenko, Phys. D (Amsterdam, Neth.) 117, 43 (1998)]. Each bush represents a dynamical object conserving the energy of the initial excitation. The existence of bushes of NNMs is ensured by some group-theoretical selection rules. In G. M. Chechin et al. [Int. J. Nonlinear Mech. 38, 1451 (2003)], existence and stability of the bushes of vibrational modes in the simple octahedral model of mass points interacting via Lennard-Jones potential were investigated. In the present paper, we study these dynamical objects by the density functional theory in the SF(6) molecule, which possesses the same symmetry and structure. We have fully confirmed the results previously obtained in the framework of the group-theoretical approach and have found some properties of the bushes of NNMs.

Three-dimensional personalized dosimetry for 188Re liver selective internal radiation therapy based on quantitative post-treatment SPECT studies.

We demonstrate that accurate patient-specific distributions of microspheres labeled with 188Re and resulting absorbed doses can be obtained from single-photon emission computed tomography (SPECT) studies performed after 188Re selective internal radiation therapy when accurate correction methods are employed in image reconstruction. Our quantitative image reconstruction algorithm includes corrections for attenuation, resolution degradations and scatter as well as a window-based compensation for contamination. The procedure has been validated using four phantom experiments containing an 18 ml cylindrical source (82-93 MBq of 188Re activity) simulating a liver tumor. In addition, we applied our approach to post-therapy SPECT studies of ten patients with progressive primary or metastatic liver carcinomas. Our quantitative algorithm accurately (within 9%) recovered 188Re activity from four phantom experiments. In addition, for two patients that received three scans, deviations remained consistent between the measured and the reconstructed activities that were determined from studies with differing severity of the dead-time effect. The analysis of absorbed doses for patient studies allowed us to hypothesize that D90 (the minimum dose received by 90% of the tumor volume) may be a reliable metric relating therapy outcomes to the calculated doses. Among several considered metrics, only D90 showed statistically significant correlation with the overall survival.

Simulation-based reconstruction of absolute activities from the (99m)Tc/(111)In dual-isotope SPECT/CT: phantom experiments and imaging of neuroendocrine tumors.

We investigate the quantitative accuracy of the reconstruction of absolute (99m)Tc and (111)In activities from (99m)Tc/(111)In dual-isotope SPECT studies. The separate reconstruction of two images is achieved by applying Monte Carlo simulation-based corrections for self-scatter and cross-talk between energy windows. For method evaluation, a series of (99m)Tc/(111)In physical phantom experiments was performed using a clinical SPECT/CT camera. The containers were filled with different ratios of (99m)Tc and (111)In activities to create cross-talk with varying severity levels. In addition, we illustrate the performance of our method by reconstructing images from four simultaneous (99m)Tc/(111)In SPECT/CT studies of neuroendocrine patients. Similarly to the phantom experiments, clinical cases provide examples with different severity of cross-talk. Phantom experiments showed that Monte Carlo simulation-based corrections improved both quantitative accuracy and visual properties of (99m)Tc and (111)In images. While the errors of absolute activities for both tracers in six containers ranged from 16% to 75% if no corrections for self-scatter and cross-talk were applied, these errors decreased to below 10% when images were reconstructed with the aforementioned corrections. These activities were measured using regions of interest larger than the true sizes of the containers in order to account for the spill-out effect. Analysis of patient studies confirmed that accurate simulation-based compensations improved resolution and contrast for both (99m)Tc and (111)In images.

Two methods to generate templates for template-based partial volume effect correction: SPECT phantom experiments.

In this paper, we explore the applicability of template-based compensation for the partial volume effect (PVE) for situations where (i) the image has multiple uptake sites (tumors and organs) but only one of them is treated as a region of interest (ROI) with the boundaries available from a high-resolution modality and (ii) no information regarding activities inside or outside this ROI is a priori available. We modeled this situation by performing SPECT acquisitions of phantoms containing 21 containers, which had different shapes and sizes and were filled with different levels of activity. In our analysis, each of these containers was treated as an individual ROI. We compared the performance of two methods of template construction. In method 1, the ROI template value was obtained from a conventionally reconstructed (without PVEC) image. In method 2, the ROI template value was directly (bypassing the PVE-affected conventional image) calculated from projections using region-based reconstruction. Our processing shows that method 1 resulted in consistent (activities for all 21 ROIs were improved) but relatively weak PVE compensation (errors of recovered total activities were equal to or lower than 10% for 5 ROIs only). Application of method 2 resulted in a selective (activities for 19 ROIs were improved) but considerably better compensation when compared to method 1 (errors of recovered total activities were equal to or lower than 10% for 10 ROIs).

Quantitative SPECT/CT reconstruction for ¹77Lu and ¹77Lu/9°Y targeted radionuclide therapies.

We investigated the quantitative accuracy of SPECT/CT imaging studies as would be performed before and after targeted radionuclide therapy (TRT) using phantom experiments with (i) (99m)Tc, (ii) ¹77Lu and (iii) 9°Y/¹77Lu. While the experiment with (99m)Tc imitated a diagnostic scan, the experiments with ¹77Lu and 9°Y/¹77Lu modeled post-therapy acquisitions. At the next stage, we reconstructed images from pre- and post-therapy patient studies. The data were first reconstructed using two methods with limited corrections for the physics effects. Then, to generate quantitatively accurate absolute activity distributions, we applied a hybrid (model-based and window-based) reconstruction strategy where some of the physics effects were accurately modeled while corrections for other effects were empirical and based on information obtained from the projection data. The accuracies of absolute activity recovered by the hybrid method from the six phantom experiments were very similar to each other and acceptable for potential use in TRT. When measured in identical regions of interest, the (99m)Tc 9°activity was reconstructed with errors ranging between -3.3% and 2.9%, while the ¹77Lu activity was reconstructed from experiments with ¹77Lu and Y/¹77Lu with errors ranging between -1.6% and 1.6%. The reconstruction algorithms with limited corrections led to larger and case-specific errors as might have been expected. From a clinical prospective, our results showed that physics-based reconstructions improved resolution of images corresponding to both diagnostic scans with (99m)Tc and post-therapy scans with ¹77Lu. Our analysis of patient study demonstrated that lack of corrections led to overestimation of activities in organs and tumor by 29-39% for the diagnostic scan with (99m)Tc and by 105-218% for post-therapy scan with ¹77Lu.

Quantitative image reconstruction for dual-isotope parathyroid SPECT/CT: phantom experiments and sample patient studies.

We investigated the quantitative accuracy of the model-based dual-isotope single-photon emission computed tomography (DI-SPECT) reconstructions that use Klein-Nishina expressions to estimate the scattered photon contributions to the projection data. Our objective was to examine the ability of the method to recover the absolute activities pertaining to both radiotracers: Tc-99m and I-123. We validated our method through a series of phantom experiments performed using a clinical hybrid SPECT/CT camera (Infinia Hawkeye, GE Healthcare). Different activity ratios and different attenuating media were used in these experiments to create cross-talk effects of varying severity, which can occur in clinical studies. Accurate model-based corrections for scatter and cross-talk with CT attenuation maps allowed for the recovery of the absolute activities from DI-SPECT/CT scans with errors that ranged 0-10% for both radiotracers. The unfavorable activity ratios increased the computational burden but practically did not affect the resulting accuracy. The visual analysis of parathyroid patient data demonstrated that our model-based processing improved adenoma/background contrast and enhanced localization of small or faint adenomas.

An innovative iterative thresholding algorithm for tumour segmentation and volumetric quantification on SPECT images: Monte Carlo-based methodology and validation.

PURPOSE: Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) imaging play an important role in the segmentation of functioning parts of organs or tumours, but an accurate and reproducible delineation is still a challenging task. In this work, an innovative iterative thresholding method for tumour segmentation has been proposed and implemented for a SPECT system. This method, which is based on experimental threshold-volume calibrations, implements also the recovery coefficients (RC) of the imaging system, so it has been called recovering iterative thresholding method (RIThM). The possibility to employ Monte Carlo (MC) simulations for system calibration was also investigated. METHODS: The RIThM is an iterative algorithm coded using MATLAB: after an initial rough estimate of the volume of interest, the following calculations are repeated: (i) the corresponding source-to-background ratio (SBR) is measured and corrected by means of the RC curve; (ii) the threshold corresponding to the amended SBR value and the volume estimate is then found using threshold-volume data; (iii) new volume estimate is obtained by image thresholding. The process goes on until convergence. The RIThM was implemented for an Infinia Hawkeye 4 (GE Healthcare) SPECT/CT system, using a Jaszczak phantom and several test objects. Two MC codes were tested to simulate the calibration images: SIMIND and SimSet. For validation, test images consisting of hot spheres and some anatomical structures of the Zubal head phantom were simulated with SIMIND code. Additional test objects (flasks and vials) were also imaged experimentally. Finally, the RIThM was applied to evaluate three cases of brain metastases and two cases of high grade gliomas. RESULTS: Comparing experimental thresholds and those obtained by MC simulations, a maximum difference of about 4% was found, within the errors (+/- 2% and +/- 5%, for volumes > or = 5 ml or < 5 ml, respectively). Also for the RC data, the comparison showed differences (up to 8%) within the assigned error (+/- 6%). ANOVA test demonstrated that the calibration results (in terms of thresholds or RCs at various volumes) obtained by MC simulations were indistinguishable from those obtained experimentally. The accuracy in volume determination for the simulated hot spheres was between -9% and 15% in the range 4-270 ml, whereas for volumes less than 4 ml (in the range 1-3 ml) the difference increased abruptly reaching values greater than 100%. For the Zubal head phantom, errors ranged between 9% and 18%. For the experimental test images, the accuracy level was within +/- 10%, for volumes in the range 20-110 ml. The preliminary test of application on patients evidenced the suitability of the method in a clinical setting. CONCLUSIONS: The MC-guided delineation of tumor volume may reduce the acquisition time required for the experimental calibration. Analysis of images of several simulated and experimental test objects, Zubal head phantom and clinical cases demonstrated the robustness, suitability, accuracy, and speed of the proposed method. Nevertheless, studies concerning tumors of irregular shape and/or nonuniform distribution of the background activity are still in progress.

Assessment of the severity of partial volume effects and the performance of two template-based correction methods in a SPECT/CT phantom experiment.

We investigated the severity of partial volume effects (PVE), which may occur in SPECT/CT studies, and the performance of two template-based correction techniques. A hybrid SPECT/CT system was used to scan a thorax phantom that included lungs, a heart insert and six cylindrical containers of different sizes and activity concentrations. This phantom configuration allowed us to have non-uniform background activity and a combination of spill-in and spill-out effects for several compartments. The reconstruction with corrections for attenuation, scatter and resolution loss but not PVE correction accurately recovered absolute activities in large organs. However, the activities inside segmented 17-120 mL containers were underestimated by 20%-40%. After applying our PVE correction to the data pertaining to six small containers, the accuracy of the recovered total activity improved with errors ranging between 3% and 22% (non-iterative method) and between 5% and 15% (method with an iteratively updated background activity). While the non-iterative template-based algorithm demonstrated slightly better accuracy for cases with less severe PVE than the iterative algorithm, it underperformed in situations with considerable spill out and/or mixture of spill-in and spill-out effects.

Quantitative accuracy of the closed-form least-squares solution for targeted SPECT.

The aim of this study is to investigate the quantitative accuracy of the closed-form least-squares solution (LSS) for single photon emission computed tomography (SPECT). The main limitation for employing this method in actual clinical reconstructions is the computational cost related to operations with a large-sized system matrix. However, in some clinical situations, the size of the system matrix can be decreased using targeted reconstruction. For example, some oncology SPECT studies are characterized by intense tracer uptakes that are localized in relatively small areas, while the remaining parts of the patient body have only a low activity background. Conventional procedures reconstruct the activity distribution in the whole object, which leads to relatively poor image accuracy/resolution for tumors while computer resources are wasted, trying to rebuild diagnostically useless background. In this study, we apply a concept of targeted reconstruction to SPECT phantom experiments imitating such oncology scans. Our approach includes two major components: (i) disconnection of the entire imaging system of equations and extraction of only those parts that correspond to the targets, i.e., regions of interest (ROI) encompassing active containers/tumors and (ii) generation of the closed-form LSS for each target ROI. We compared these ROI-based LSS with those reconstructed by the conventional MLEM approach. The analysis of the five processed cases from two phantom experiments demonstrated that the LSS approach outperformed MLEM in terms of the noise level inside ROI. On the other hand, MLEM better recovered total activity if the number of iterations was large enough. For the experiment without background activity, the ROI-based LSS led to noticeably better spatial activity distribution inside ROI. However, the distributions pertaining to both approaches were practically identical for the experiment with the concentration ratio 7:1 between the containers and the background.

An enhancement of quantitative accuracy of the SPECT/CT activity distribution reconstructions: Physical phantom experiments.

For many clinical SPECT studies, it is important to know not only the total activity in an organ of interest, but also the details regarding the activity distribution. In our approach, the anatomical information significantly contributes to improve reconstructed images through CT-based attenuation, scatter, and voxelized partial volume effect corrections. Our method uses the low dose CT image of each particular organ or object (e.g., tumor) to create an object-specific numeric template. Assuming that the sequential projection and reconstruction of this template result in a similar deterioration as in the real image, the template information is being used to correct this image on a voxel-by-voxel basis. In our phantom experiments using clinical camera and protocols, we recovered total activities with errors less than approximately 6% for 33ml tumor models and approximately 9% for 120ml heart insert.

Complexity and accuracy of image registration methods in SPECT-guided radiation therapy.

The use of functional imaging in radiotherapy treatment (RT) planning requires accurate co-registration of functional imaging scans to CT scans. We evaluated six methods of image registration for use in SPECT-guided radiotherapy treatment planning. Methods varied in complexity from 3D affine transform based on control points to diffeomorphic demons and level set non-rigid registration. Ten lung cancer patients underwent perfusion SPECT-scans prior to their radiotherapy. CT images from a hybrid SPECT/CT scanner were registered to a planning CT, and then the same transformation was applied to the SPECT images. According to registration evaluation measures computed based on the intensity difference between the registered CT images or based on target registration error, non-rigid registrations provided a higher degree of accuracy than rigid methods. However, due to the irregularities in some of the obtained deformation fields, warping the SPECT using these fields may result in unacceptable changes to the SPECT intensity distribution that would preclude use in RT planning. Moreover, the differences between intensity histograms in the original and registered SPECT image sets were the largest for diffeomorphic demons and level set methods. In conclusion, the use of intensity-based validation measures alone is not sufficient for SPECT/CT registration for RTTP. It was also found that the proper evaluation of image registration requires the use of several accuracy metrics.

[Comparison of the results of magnetic resonance urography and other examination methods in patients with iatrogenic injuries of the ureter and pelvis-ureteral segment].

MR urography was made in 25 patients (age 24-70, mean age 48.6 years, 20 females, 5 males) with iatrogenic injury of the upper urinary tract (UUT). A comparison group consisted of 15 patients without nephrostomic drainage who had no contraindications for intravenous contrast preparations. MR urography was performed in frontal and sagittal projections. The examination was made before and 20 min after intravenous injection of 20 mg diuretic. Five patients received additionally excretory MR urography with intravenous injection of magnevist (0.2 ml/kg, 3 ml/s just before the examination). Mean duration of urography was 21 (18-23) min. The results were compared to findings of ultrasound or x-ray investigations, diapevtic ureteroscopy or open surgical intervention. The results were similar to those of x-ray CT. In patients with ureteral obliteration MR urography was less informative than joint antegrade and retrograde ureteropyelography as the ureter could not be visualized beneath the injury. In 2 patients examined with intravenous urography and x-ray CT, definite length of ureteral stricture was obtained only with MR urography. In 5 patients with hydronephrotic transformation MR urography was much more informative than excretory urography. MR urography provided information sufficient for diagnosis. Sensitivity of MR urography and that with diuretic load was 86.8 and 92.3%, respectively. MR urography, even without contrast enhancement, provides images with high resolution sufficient for visualization of the ureter distally of the stricture and is a method of choice in patients with subnormal renal function, intolerance to iodine-containing contrast media, with hyperthyroidism and pregnant women after the first trimester.

An APD-based iterative reconstruction method for simultaneous technetium-99m/iodine-123 SPECT imaging.

Dual-isotope SPECT (DI-SPECT) studies offer significant advantages over sequential scans, foremost among them faster acquisition and perfect image registration. However, reconstructed images may be affected by substantial cross-talk contamination rendering them inadequate for diagnosis. This effect is especially strong for isotopes with close photopeak energies, such as (99m)Tc (140keV) and (123)I (159keV). In this paper we present an iterative DI-SPECT reconstruction method which includes accurate, analytically computed scatter corrections provided by the APD (analytical photon distribution) algorithm. This algorithm calculates first and second order Compton scatter (based on the Klein-Nishina formula) and first order Rayleigh scatter. Both self-scatter and cross-talk between the two isotopes are evaluated using patient specific attenuation maps and an initial activity distribution estimate. To validate our method we performed experiments using the Data Spectrum, Inc. thorax phantom and a SPECT/CT camera system. Reconstructed images demonstrate significant improvement in data quantitation. Their quantitative accuracy increases up to a factor of two, even for activity ratios which strongly enhance cross-talk effects and seriously degrade projections.

Accuracy of quantitative reconstructions in SPECT/CT imaging.

The goal of this study was to determine the quantitative accuracy of our OSEM-APDI reconstruction method based on SPECT/CT imaging for Tc-99m, In-111, I-123, and I-131 isotopes. Phantom studies were performed on a SPECT/low-dose multislice CT system (Infinia-Hawkeye-4 slice, GE Healthcare) using clinical acquisition protocols. Two radioactive sources were centrally and peripherally placed inside an anthropometric Thorax phantom filled with non-radioactive water. Corrections for attenuation, scatter, collimator blurring and collimator septal penetration were applied and their contribution to the overall accuracy of the reconstruction was evaluated. Reconstruction with the most comprehensive set of corrections resulted in activity estimation with error levels of 3-5% for all the isotopes.