Clinical feasibility and impact of data-driven respiratory motion compensation studied in 200 whole-body 18F-FDG PET/CT scans.

BACKGROUND: This study examines the clinical feasibility and impact of implementing a fully automated whole-body PET protocol with data-driven respiratory gating in patients with a broad range of oncological and non-oncological pathologies 592 FDG PET/CT patients were prospectively included. 200 patients with lesions in the torso were selected for further analysis, and ungated (UG), belt gated (BG) and data-driven gating (DDG) images were reconstructed. All images were reconstructed using the same data and without prolonged acquisition time for gated images. Images were quantitatively analysed for lesion uptake and metabolic volume, complemented by a qualitative analysis of visual lesion detection. In addition, the impact of gating on treatment response evaluation was evaluated in 23 patients with malignant lymphoma. RESULTS: Placement of the belt needed for BG was associated with problems in 27% of the BG scans, whereas no issues were reported using DDG imaging. For lesion quantification, DDG and BG images had significantly greater SUV values and smaller volumes than UG. The physicians reported notable image blurring in 44% of the UG images that was problematic for clinical evaluation in 4.5% of cases. CONCLUSION: Respiratory motion compensation using DDG is readily integrated into clinical routine and produce images with more accurate and significantly greater SUV values and smaller metabolic volumes. In our broad cohort of patients, the physicians overwhelmingly preferred gated over ungated images, with a slight preference for DDG images. However, even in patients with malignant disease in the torso, no additional diagnostic information was obtained by the gated images that could not be derived from the ungated images.

Clinical Evaluation of a Data-Driven Respiratory Gating Algorithm for Whole-Body PET with Continuous Bed Motion.

Respiratory gating is the standard to prevent respiration effects from degrading image quality in PET. Data-driven gating (DDG) using signals derived from PET raw data is a promising alternative to gating approaches requiring additional hardware (e.g., pressure-sensitive belt gating [BG]). However, continuous-bed-motion (CBM) scans require dedicated DDG approaches for axially extended PET, compared with DDG for conventional step-and-shoot scans. In this study, a CBM-capable DDG algorithm was investigated in a clinical cohort and compared with BG using optimally gated (OG) and fully motion-corrected (elastic motion correction [EMOCO]) reconstructions. Methods: Fifty-six patients with suspected malignancies in the thorax or abdomen underwent whole-body 18F-FDG CBM PET/CT using DDG and BG. Correlation analyses were performed on both gating signals. Besides static reconstructions, OG and EMOCO reconstructions were used for BG and DDG. The metabolic volume, SUVmax, and SUVmean of lesions were compared among the reconstructions. Additionally, the quality of lesion delineation in the different PET reconstructions was independently evaluated by 3 experts. Results: The global correlation coefficient between BG and DDG signals was 0.48 ± 0.11, peaking at 0.89 ± 0.07 when scanning the kidney and liver region. In total, 196 lesions were analyzed. SUV measurements were significantly higher in BG-OG, DDG-OG, BG-EMOCO, and DDG-EMOCO than in static images (P < 0.001; median SUVmax: static, 14.3 ± 13.4; BG-EMOCO, 19.8 ± 15.7; DDG-EMOCO, 20.5 ± 15.6; BG-OG, 19.6 ± 17.1; and DDG-OG, 18.9 ± 16.6). No significant differences between BG-OG and DDG-OG or between BG-EMOCO and DDG-EMOCO were found. Visual lesion delineation was significantly better in BG-EMOCO and DDG-EMOCO than in static reconstructions (P < 0.001); no significant difference was found when comparing BG and DDG for either EMOCO or OG reconstruction. Conclusion: DDG-based motion compensation of CBM PET acquisitions outperforms static reconstructions, delivering qualities comparable to BG approaches. The new algorithm may be a valuable alternative for CBM PET systems.

Feasibility of simultaneous PET-MR perfusion using a novel cardiac perfusion phantom.

BACKGROUND: PET-MR scanners are beginning to be employed for quantitative myocardial perfusion imaging. In order to examine simultaneous perfusion calculations, this work describes a feasibility study of simultaneous PET-MR of gadolinium-based contrast agent (GBCA) and PET radiotracer in a novel cardiac perfusion phantom. RESULTS: [18F]F- and GBCA were injected simultaneously into a cardiac phantom using a range of ground-truth myocardial perfusion rates of 1 to 5 ml/g/min. PET quantification of K1 (ml/g/min) was performed using a single tissue compartment model. MR perfusion was calculated using a model-independent signal deconvolution technique. PET and MR signal traces from the phantom aorta and myocardial sections show true simultaneous PET and MR arterial input functions (AIF) and myocardial uptake respectively at each perfusion rate. Calculation of perfusion parameters showed both K1 and h(t = 0) (PET and MR perfusion parameters respectively) to be linearly related with the ground truth perfusion rate (PT ), and also linearly related to each other (R2 = 0.99). The highest difference in perfusion values between K1 and PT was 16% at 1 ml/g/min, and the mean difference for all other perfusion rates was <3%. CONCLUSIONS: The perfusion phantom allows accurate and reproducible simulation of the myocardial kinetics for simultaneous PET-MR imaging, and may find use in protocol design and development of PET-MR based quantification techniques and direct comparison of quantification of the two modalities.

Pitfalls and Artifacts in the Use of PET/CT in Oncology Imaging.

Accurate reporting of combined PET/CT imaging requires a thorough understanding of the normal and variant physiological distribution of tracers as well as common incidental findings and technical artifacts. We describe these pitfalls and artifacts, what action may help to mitigate them in clinical practice, and what further action may be appropriate. This review presents these in a region-based approach, in order to closely mimic clinical practice, and focuses on technical artifacts followed by a description of two commonly used oncologic tracers: FDG and choline.

An Experimentally Established Key Intermediate in Benzene Nitration with Mixed Acid.

Experimental evidence is reported for the first intermediate in the classic SEAr reaction of benzene nitration with mixed acid. The UV/Vis spectroscopic investigation of the reaction showed an intense absorption at 320 nm (appearing as a band shoulder) arising from a reaction intermediate. Our theoretical modeling shows that the interaction between the two principal reactants with solvent (H2SO4) molecules significantly affects the structure of the initial complex. In this complex, a larger distance between the aromatic ring and nitronium ion precludes the possibility for electronic charge transfer from the benzene π-system to the electrophile. The computational modeling of the potential energy surface reveals that the reaction favors a stepwise mechanism with intermediate formation of π- and σ-(arenium ion) complexes.

Structural isomerization of the gas-phase 2-norbornyl cation revealed with infrared spectroscopy and computational chemistry.

In an attempt to produce the 2-norbornyl cation (2NB(+)) in the gas phase, protonation of norbornene was accomplished in a pulsed discharge ion source coupled with a supersonic molecular beam. The C7H11(+) cation was size-selected in a time-of-flight mass spectrometer and investigated with infrared laser photodissociation spectroscopy using the method of "tagging" with argon. The resulting vibrational spectrum, containing sharp bands in the C-H stretching and fingerprint regions, was compared to that predicted by computational chemistry. However, the measured spectrum did not match that of 2NB(+), prompting a detailed computational study of other possible isomers of C7H11(+). This study finds five isomers more stable than 2NB(+). The spectrum obtained corresponds to the 1,3-dimethylcyclopentenyl cation, the global minimum-energy structure for C7H11(+), which is produced through an unanticipated ring-opening rearrangement path.

On transcending the impasse of respiratory motion correction applications in routine clinical imaging - a consideration of a fully automated data driven motion control framework.

Positron emission tomography (PET) is increasingly used for the detection, characterization, and follow-up of tumors located in the thorax. However, patient respiratory motion presents a unique limitation that hinders the application of high-resolution PET technology for this type of imaging. Efforts to transcend this limitation have been underway for more than a decade, yet PET remains for practical considerations a modality vulnerable to motion-induced image degradation. Respiratory motion control is not employed in routine clinical operations. In this article, we take an opportunity to highlight some of the recent advancements in data-driven motion control strategies and how they may form an underpinning for what we are presenting as a fully automated data-driven motion control framework. This framework represents an alternative direction for future endeavors in motion control and can conceptually connect individual focused studies with a strategy for addressing big picture challenges and goals.

Carbene-stabilized beryllium borohydride.

The reaction of N-heterocyclic carbene, L:, with BeCl(2) quantitatively yields L:BeCl(2)1 (L: = :C{N(2,6-Pr(i)(2)C(6)H(3))CH}(2)). The carbene-stabilized beryllium borohydride monomer L:Be(BH(4))(2)2 is prepared by the reaction of 1 with LiBH(4). Compound 3, prepared by the reaction of 2 with Na(2)[Fe(CO)(4)]·dioxane, represents an unusual "dual reduction" of the imidazole ring (i.e., hydroboration of the C═C backbone and hydrogenation of the C2 carbene center).

Extension of a data-driven gating technique to 3D, whole body PET studies.

Respiratory gating can be used to separate a PET acquisition into a series of near motion-free bins. This is typically done using additional gating hardware; however, software-based methods can derive the respiratory signal from the acquired data itself. The aim of this work was to extend a data-driven respiratory gating method to acquire gated, 3D, whole body PET images of clinical patients. The existing method, previously demonstrated with 2D, single bed-position data, uses a spectral analysis to find regions in raw PET data which are subject to respiratory motion. The change in counts over time within these regions is then used to estimate the respiratory signal of the patient. In this work, the gating method was adapted to only accept lines of response from a reduced set of axial angles, and the respiratory frequency derived from the lung bed position was used to help identify the respiratory frequency in all other bed positions. As the respiratory signal does not identify the direction of motion, a registration-based technique was developed to align the direction for all bed positions. Data from 11 clinical FDG PET patients were acquired, and an optical respiratory monitor was used to provide a hardware-based signal for comparison. All data were gated using both the data-driven and hardware methods, and reconstructed. The centre of mass of manually defined regions on gated images was calculated, and the overall displacement was defined as the change in the centre of mass between the first and last gates. The mean displacement was 10.3 mm for the data-driven gated images and 9.1 mm for the hardware gated images. No significant difference was found between the two gating methods when comparing the displacement values. The adapted data-driven gating method was demonstrated to successfully produce respiratory gated, 3D, whole body, clinical PET acquisitions.

Starlike aluminum-carbon aromatic species.

Is it possible to achieve molecules with starlike structures by replacing the H atoms in (CH)(n)(q) aromatic hydrocarbons with aluminum atoms in bridging positions? Although D(4h) C(4)Al(4)(2-) and D(2) C(6)Al(6) are not good prospects for experimental realization, a very extensive computational survey of fifty C(5)Al(5)(-) isomers identified the starlike D(5h) global minimum with five planar tetracoordinate carbon atoms to be a promising candidate for detection by photoelectron detachment spectroscopy. BOMD (Born-Oppenheimer molecular dynamics) simulations and high-level theoretical computations verified this conclusion. The combination of favorable electronic and geometric structural features (including aromaticity and optimum C-Al-C bridge bonding) stabilizes the C(5)Al(5)(-) star preferentially.

Communications: Infrared spectroscopy of gas phase C3H3+ ions: the cyclopropenyl and propargyl cations.

C(3)H(3)(+) ions produced with a pulsed discharge source and cooled in a supersonic beam are studied with infrared laser photodissociation spectroscopy in the 800-4000 cm(-1) region using the rare gas tagging method. Vibrational bands in the C-H stretching and fingerprint regions confirm the presence of both the cyclopropenyl and propargyl cations. Because there is a high barrier separating these two structures, they are presumed to be produced by different routes in the plasma chemistry; their relative abundance can be adjusted by varying the ion source conditions. Prominent features for the cyclopropenyl species include the asymmetric carbon stretch (nu(5)) at 1293 cm(-1) and the asymmetric C-H stretch (nu(4)) at 3182 cm(-1), whereas propargyl has the CH(2) scissors (nu(4)) at 1445, the C-C triple bond stretch (nu(3)) at 2077 and three C-H stretches (nu(2), nu(9), and nu(1)) at 3004, 3093, and 3238 cm(-1). Density functional theory computations of vibrational spectra for the two isomeric ions with and without the argon tag reproduce the experimental features qualitatively; according to theory the tag atom only perturbs the spectra slightly. Although these data confirm the accepted structural pictures of the cyclopropenyl and propargyl cations, close agreement between theoretical predictions and the measured vibrational band positions and intensities cannot be obtained. Band intensities are influenced by the energy dependence and dynamics of photodissociation, but there appear to be fundamental problems in computed band positions independent of the level of theory employed. These new data provide infrared signatures in the fingerprint region for these prototypical carbocations that may aid in their astrophysical detection.

The effect of perfluorination on the aromaticity of benzene and heterocyclic six-membered rings.

Despite having six highly electronegative F's, perfluorobenzene C(6)F(6) is as aromatic as benzene. Ab initio block-localized wave function (BLW) computations reveal that both C(6)F(6) and benzene have essentially the same extra cyclic resonance energies (ECREs). Localized molecular orbital (LMO)-nucleus-independent chemical shifts (NICS) grids demonstrates that the F's induce only local paratropic contributions that are not related to aromaticity. Thus, all of the fluorinated benzenes (C(6)F(n)H((6-n)), n = 1-6) have similar ring-LMO-NICS(pi zz) values. However, 1,3-difluorobenzene 2b and 1,3,5-trifluorobenzene 3c are slightly less aromatic than their isomers due to a greater degree of ring charge alternation. Isoelectronic C(5)H(5)Y heterocycles (Y = BH(-), N, NH(+)) are as aromatic as benzene, based on their ring-LMO-NICS(pi zz) and ECRE values, unless extremely electronegative heteroatoms (e.g., Y = O(+)) are involved.

Cyclic boron clusters enclosing planar hypercoordinate cobalt, iron, and nickel.

Planar cyclic boron clusters with cobalt, iron, and nickel atoms at their centerssinglet D(8h) CoB(8)(-), D(9h) FeB(9)(-), CoB(9), and NiB(9)(+)are computed to be stable minima at the BP86/TZVPP DFT level. Stochastic searches of the singlet and triplet potential energy surfaces show the planar hypercoordinate D(8h) CoB(8)(-) (1) and D(9h) FeB(9)(-) (2) singlet isomers to be the global minima. Their double aromatic character with 6 pi and 10 radial electrons is documented by detailed NICS(zz) grid and CMO-NICS(zz) analyses at PW91/TZVPP. These results encourage gas phase investigations of these two exotic anions. Although isoelectronic with D(9h) FeB(9)(-) (2), CoB(9) and NiB(9)(+) prefer nonplanar structures, triplet 3-aT for the former and singlet 4-a for the latter.

Planar tetracoordinate carbon species involving beryllium substituents.

Planar tetracoordinate carbon (ptC) arrangements can be achieved by employing multiple substituents based on beryllium, despite its rather weak pi-acceptor ability. A variety of ptC-containing examples, some with more than one ptC, have been designed computationally by elaborating the planar C(BeH) 4 (2-) prototype at B3LYP/6-311++G(3df,2p) and MP2/6-311++G(3df,2p) levels of theory for some small ptC representatives. The prototype prefers a D(2h) paramagnetic triplet ground state due to Hund's rule, rather than a singlet. The highly polarized C-Be bonding weakens the rigidity of the tetrahedral carbon in T(d)C(BeH) 4 enormously, and the enhancement of both C-Be and Be 4 peripheral covalent bonding exerted by the extra electrons stabilizes the ptC eventually. The delocalization of the two p pi electrons is only modest, but their density on the most electronegative carbon atom helps stabilize the ptC arrangement. This is in contrast to the conventional strategy to delocalize p(pi) lone pairs for stabilizing the ptC arrangement. Various strategies to achieve neutral derivatives with ptCs are demonstrated.

Infrared spectroscopy of gas phase C3H5+ : the allyl and 2-propenyl cations.

C3H5+ cations are probed with infrared photodissociation spectroscopy in the 800-3500 cm(-1) region using the method of rare gas tagging. The ions and their complexes with Ar or N2 are produced in a pulsed electric discharge supersonic expansion cluster source. Two structural isomers are characterized, namely, the allyl (CH2CHCH2+) and 2-propenyl (CH3CCH2+) cations. The infrared spectrum of the allyl cation confirms previous theoretical and condensed phase studies of the C(2nu) charge delocalized, resonance-stabilized structure. The 2-propenyl cation spectrum is consistent with a C(s) symmetry structure having a nearly linear CCC backbone and a hyperconjugatively stabilizing methyl group.

Popular theoretical methods predict benzene and arenes to be nonplanar.

Planar (D6h) benzene has one (1181i cm-1, b2g) and three (1844i cm-1, b2g; 462i cm-1, e2u) imaginary vibrational frequencies at the MP2/6-311++G(d,p) and MP2/6-311++G levels of theory, respectively! The spurious frequencies correspond to D3d chair (b2g) and C2v boat (e2u) out-of-plane distortions. Numerous, similar examples where planar benzene is not a minimum are documented at the MP2, MP3, and CISD levels with popular Pople-type basis sets, while the RHF, B3LYP, and BLYP methods exhibit no such problems. We show that, in the sp and spd atomic-orbital limits of MP2 theory, benzene is nonplanar. The observed failure of electron correlation methods with unbalanced basis sets to predict planar minima is not unique to benzene but is also found for other pi-delocalized molecules, including pyridine, naphthalene, anthracene, the cyclopentadienyl and indenyl anions, and the tropylium cation. Detailed mathematical analysis reveals that an insidious, geometry-dependent, two-electron basis set incompleteness error (BSIE) is responsible for the problem and that balanced, correlation-consistent constructions of basis sets are generally required to ensure reliable predictions for arenes with correlated wave functions.

Phase I trial of 131I-huA33 in patients with advanced colorectal carcinoma.

PURPOSE: Humanized monoclonal antibody A33 (huA33) targets the A33 antigen which is expressed on 95% of colorectal cancers. A previous study has shown excellent tumor-targeting of iodine-131 labeled huA33 (131I-huA33). Therefore, we did a phase I dose escalation trial of 131I-huA33 radioimmunotherapy. EXPERIMENTAL DESIGNS: Fifteen patients with pretreated metastatic colorectal carcinoma each received two i.v. doses of 131I-huA33. The first was an outpatient trace-labeled "scout" dose for biodistribution assessment, followed by a second "therapy" dose. Three patients were treated at 20, 30, and 40 mCi/m2 dose levels, and six patients at 50 mCi/m2 to define the maximum tolerated dose. RESULTS: Hematologic toxicity was 131I dose-dependent, with one episode of grade 4 neutropenia and two episodes of grade 3 thrombocytopenia observed at 50 mCi/m2. The maximum tolerated dose was determined to be 40 mCi/m2. There were no acute infusion-related adverse events, and gastrointestinal toxicity was not observed despite uptake of 131I-huA33 in bowel. Seven patients developed pruritus or rash, which was not related to 131I dose. There was excellent tumor-targeting of 131I-huA33 shown in all patients. The serum T1/2beta of 131I-huA33 was (mean +/- SD) 135.2 +/- 46.9 hours. The mean absorbed tumor dose was 6.49 +/- 2.47 Gy/GBq. Four patients developed human anti-human antibodies. At restaging, 4 patients had stable disease, whereas 11 patients had progressive disease. CONCLUSION: Radioimmunotherapy using 131I-huA33 shows promise in targeting colorectal tumors, and is deliverable at a maximum tolerated dose of 40 mCi/m2. Further studies of 131I-huA33 in combination with chemotherapy are planned.