P.E. Kinahan

Attenuation correction for a combined 3D PET/CT scanner

In this work we demonstrate the proof of principle of CT-based attenuation correction of 3D positron emission tomography (PET) data by using scans of bone and soft tissue equivalent phantoms and scans of humans. This method of attenuation correction is intended for use in a single scanner that combines volume-imaging (3D) PET with x-ray computed tomography (CT) for the purpose of providing accurately registered anatomical localization of structures seen in the PET image. The goal of this work is to determine if we can perform attenuation correction of the PET emission data using accurately aligned CT attenuation information. We discuss possible methods of calculating the PET attenuation map at 511 keV based on CT transmission information acquired from 40 keV through 140 keV. Data were acquired on separate CT and PET scanners and were aligned using standard image registration procedures. Results are presented on three of the attenuation calculation methods: segmentation, scaling, and our proposed hybrid segmentation/scaling method. The results are compared with those using the standard 3D PET attenuation correction method as a gold standard. We demonstrate the efficacy of our proposed hybrid method for converting the CT attenuation map from an effective CT photon energy of 70 keV to the PET photon energy of 511 keV. We conclude that using CT information is a feasible way to obtain attenuation correction factors for 3D PET.

Amphetamine-induced dopamine release in human ventral striatum correlates with euphoria

BACKGROUND Studies in experimental animals have implicated the mesolimbic dopaminergic projections into the ventral striatum in the neural processes underlying behavioral reinforcement and motivated behavior; however, understanding the relationship between subjective emotional experience and ventral striatal dopamine (DA) release has awaited human studies. Using positron emission tomography (PET), we correlated the change in endogenous dopamine concentrations following dextroamphetamine (AMPH) administration with the associated hedonic response in human subjects and compared the strength of this correlation across striatal subregions. METHODS We obtained PET measures of [(11)C]raclopride specific binding to DA D2/D3 receptors before and after AMPH injection (0.3 mg/kg IV) in seven healthy subjects. The change in [(11)C]raclopride binding potential (DeltaBP) induced by AMPH pretreatment and the correlation between DeltaBP and the euphoric response to AMPH were compared between the anteroventral striatum (AVS; comprised of accumbens area, ventromedial caudate, and anteroventral putamen) and the dorsal caudate (DCA) using an MRI-based region of interest analysis of the PET data. RESULTS The mean DeltaBP was greater in the AVS than in the DCA (p <.05). The AMPH-induced changes in euphoria analog scale scores correlated inversely with DeltaBP in the AVS (r = -.95; p <.001), but not in the DCA (r =.30, ns). Post hoc assessments showed that changes in tension-anxiety ratings correlated positively with DeltaBP in the AVS (r =.80; p [uncorrected] <.05) and that similar relationships may exist between DeltaBP and emotion ratings in the ventral putamen (as were found in the AVS). CONCLUSIONS The preferential sensitivity of the ventral striatum to the DA releasing effects of AMPH previously demonstrated in experimental animals extends to humans. The magnitude of ventral striatal DA release correlates positively with the hedonic response to AMPH.

Combined PET/CT Imaging in Oncology: Impact on Patient Management

Purpose: In this work, we describe five oncology patients whose clinical management were uniquely benefited by a novel scanner that acquires positron emission tomography (PET) and x-ray computed tomography (CT) in the same imaging session.Procedures: Co-registered 2-[F(18)]-fluoro-2-deoxy-D-glucose (FDG)-PET and CT images were acquired using a combined PET/CT scanner. Pathology and clinical follow-up data were used to confirm PET/CT scan results.Results: The combined PET/CT scanner demonstrated the ability to distinguish malignant lesions from normal physiologic FDG uptake in the striated muscles of the head and neck as well as excretory and bowel activity in the abdomen and pelvis. Additionally, the technology positively affected patient management through localization for surgical and radiation therapy planning as well as assessment of tumor response.Conclusion: Our experience indicates that simultaneous acquisition of co-registered PET and CT images enabled physicians to more precisely discriminate between physiologic and malignant FDG uptake and more accurately localize lesions, improving the value of diagnostic PET in oncologic applications.

Fast reconstruction of 3-D PET data with accurate statistical modeling

This paper presents the results of combining high sensitivity 3D PET whole-body acquisition followed by fast 2D iterative reconstruction methods based on accurate statistical models. This combination is made possible by Fourier rebinning (FORE), which accurately converts a 3D data set to a set of 2D sinograms. The combination of volume imaging with statistical reconstruction allows improvement of noise-bias trade-offs when image quality is dominated by measurement statistics. The rebinning of the acquired data into a 2D data set reduces the computation time of the reconstruction. For both penalized weighted least squares (PWLS) and ordered-subset EM (OSEM) reconstruction methods, the usefulness of a realistic model of the expected measurement statistics is shown when the data are pre-corrected for attenuation and random and scattered coincidences, as required for the FORE rebinning algorithm. The results presented are based on 3D simulations of whole body scans that include the major statistical effects of PET acquisition and data correction procedures. As the PWLS method requires knowledge of the variance of the projection data, a simple model for the effect of FORE rebinning on data variance is developed.

Image analysis in patients with cancer studied with a Combined PET and CT scanner

Purpose To compare combined whole-body PET and CT images of different cancers with PET images alone. Materials and Methods Thirty-two patients with known or possible cancers were examined using a combined positron emission tomographic (PET) and computed tomographic (CT) scanner. All data were acquired using this same combined scanner. After an injection of F-18 fluorodeoxyglucose (FDG), noncontrast helical CT imaging of the neck, chest, abdomen, or pelvis was performed. The spiral CT was followed by a PET scan covering the same axial extent as the CT. Results Coregistered PET–CT images identified and localized 55 lesions. In 10 patients (31%), areas with variable amounts of normal physiologic FDG uptake were distinguished from potential uptake of FDG in a nearby neoplastic lesion. Improved localization was achieved in 9 patients (for a total of 13 lesions, or 24%). Conclusion Combined PET–CT images appear more effective than PET images alone to localize precisely neoplastic lesions and to distinguish normal variants from juxtaposed neoplastic lesions.

PET Measures of Amphetamine-Induced Dopamine Release in Ventral versus Dorsal Striatum

Regional differences in dextroamphetamine (AMPH)-induced dopamine (DA) release in the baboon striatum were assessed using positron emission tomographic (PET) measures of [11C]raclopride specific binding to DA D2/D3 receptors acquired before and after AMPH administration. The magnitude of the reduction in [11C]raclopride binding, following AMPH administration, was two-fold greater in the anteroventral striatum (comprised of ventral caudate, anteroventral putamen, and nucleus accumbens) than the dorsal striatum (dorsal caudate). A simulation study demonstrated that any potential biases due to resolution (partial volume) and alignment effects were significantly smaller than the magnitude of the observed results. These regional differences in the sensitivity to AMPH are compatible with microdialysis evidence in rats indicating that the magnitude of DA release in response to AMPH concentrations in the range tested is greater in ventral than dorsal striatal regions. Post hoc tests involving measures in other striatal regions showed that the baseline DA D2/D3 binding was highest and the correlation between AMPH dose and change in [11C]raclopride binding most significant in the putamen.

[11C]WAY 100635: a radioligand for imaging 5-HT1A receptors with positron emission tomography.

The potent and selective 5-HT1A antagonist WAY 100635 (N-[2-]4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2- pyridinyl)cyclohexanecarboxamide) was radiolabeled with 11C in high specific activity, and the in vivo properties of this radioligand were assessed in the brains of rats and monkeys. Following i.v. tail vein injection in rats, [11C]WAY 100635 rapidly penetrated into brain tissue and was retained over a 30-90 min time period in a manner consistent with the known distribution of 5-HT1A receptors. Pretreatment of rats with the selective 5-HT1A agonist (+/-)-8-OH-DPAT effectively blocked the retention of radioactivity in brain regions known to contain high densities of 5-HT1A receptors. The hippocampus-to-cerebellum radioactivity concentration ratio reached a maximum of 16:1 at 60 min post injection. Following i.v. injection of [11C]WAY 100635 in rhesus monkeys, the concentrations of radioactivity in brain regions were consistent with the reported distribution of 5-HT1A receptors in primates, and the frontal cortex-to-cerebellum ratio reached 5.5:1 at 80 min post injection. Pretreatment of the monkeys with (+/-)-8-OH-DPAT reduced this ratio to 1.4:1, and injection of (+/-)-8-OH-DPAT 20 min after the injection of [11C]WAY 100635 significantly displaced frontal cortex binding. The in vivo properties of [11C]WAY 100635 in rats and monkeys strongly support the future utility of this radioligand for imaging 5-HT1A receptors using positron emission tomography (PET).

A methodology for testing for statistically significant differences between fully 3D PET reconstruction algorithms

We present a practical methodology for evaluating 3D PET reconstruction methods. It includes generation of random samples from a statistically described ensemble of 3D images resembling those to which PET would be applied in a medical situation, generation of corresponding projection data with noise and detector point spread function simulating those of a 3D PET scanner, assignment of figures of merit appropriate for the intended medical applications, optimization of the reconstruction algorithms on a training set of data, and statistical testing of the validity of hypotheses that say that two reconstruction algorithms perform equally well (from the point of view of a particular figure of merit) as compared to the alternative hypotheses that say that one of the algorithms outperforms the other. Although the methodology was developed with the 3D PET in mind, it can be used, with minor changes, for other 3D data collection methods, such as fully 3D cr or SPECT.

Simulating whole-body PET scanning with rapid analytical methods

Presents a 3D whole-body PET simulator that generates multiple, yet statistically accurate, realizations of projection data within a computation time that is short enough to enable the measurement of the task performance of image reconstruction algorithms. The whole-body simulator takes into account the following effects: the separate amounts of statistical noise contributed by true, scattered, and random coincidences, activity outside the field of view, activity decay between bed positions, detector efficiencies and resolution, and noise arising from the transmission scan. The principle of the simulation is to analytically calculate projections based on the geometrical specification of the emission and attenuation objects that comprise the MCAT phantom. A pre-determined level of statistical noise is then added to the projection data, which is then inputted to the same data correction and image reconstruction procedures used in practice. The authors compare the results of multiple realizations of simulated and measured phantom studies at statistical noise levels similar to those encountered in 3D whole-body PET scanning. They obtain comparable statistical noise properties for the fully corrected emission sinograms, and also show that a simple model accurately predicts the statistical noise added by random and scattered coincidences generated by activity outside the field of view.

The SMART scanner: a combined PET/CT tomograph for clinical oncology

A combined PET/CT tomograph with the unique capability to acquire accurately aligned functional and anatomical images for any part of the human body has been designed and built. The PET/CT, or SMART scanner, was developed by combining a Siemens Somatom AR.SP spiral CT scanner with a partial ring rotating ECAT ART PET tomograph. All components are mounted on a common rotational support within a single gantry that has an axial depth of 110 cm. The PET and CT components can be operated either separately or in combined mode. In combined mode, the CT images are used to correct the PET data for scatter and attenuation. Fully quantitative whole-body images can be obtained for an axial extent of up to 100 cm in an imaging time of less than one hour. When operated in PET mode alone, transmission scans are acquired with two 15 mCi cesium sources. We report the first performance measurements from the scanner, and present some illustrative clinical studies.