Quantitative organ time activity curve extraction from rodent PET images without anatomical prior.

PURPOSE: Numerous new drug candidates fail because of inadequate pharmacokinetics. Positron emission tomography (PET) enables the noninvasive characterization of the drug in humans and animals. The aim of the present work was the comparison of methods for the extraction of organ time activity curves from rodent PET images without requiring resort to anatomical information. METHODS: The rodent organs were segmented using the local means analysis method and the accuracy of the time activity curve (TAC) estimated using four methods was compared: The mean TAC (Mean), the TAC computed in a selection of organ voxels (ROIopt), and the TAC corrected for partial volume effect using the geometric transfer matrix (GTM) method. The accuracy of the TAC estimated using the three methods was compared on phantom simulations and on experimental data sets on mice injected with fluorothymidine. RESULTS: The segmentation quality measured on phantom simulation was 80% of overlap between segmented and gold standard organs. On the phantom simulations, the error on the TAC estimation on phantom simulations was lower for ROIopt (8%) than using the GTM (18%) and the Mean (27%) methods. Similar results were achieved on the experimental data sets: ROIopt (5.8%), GTM (9.7%), and Mean (12%). CONCLUSIONS: The new ROI optimization method was fast and precise for all homogeneous organs, while mean organ TAC computation led as expected to important errors. GTM improved the quantification accuracy but showed instabilities due to segmentation errors and to small organ sizes. Partial volume effect correction or limitation is thus possible for the extraction of precise organ TACs without requiring either manual delineation or an anatomical modality.

Basal ganglia involvement in temporal lobe epilepsy: a functional and morphologic study.

OBJECTIVES: A decrease of [(18)F]fluoro-l-dopa uptake in basal ganglia was recently reported in medically refractory epilepsy. The purpose of this study was to assess the involvement of dopaminergic neurotransmission in refractory temporal lobe epilepsy (TLE) and its relationship to glucose metabolism and morphologic changes. METHODS: Twelve TLE patients were studied using [(18)F]fluorodeoxyglucose PET, [(18)F]fluoro-l-dopa PET, and MRI and compared with healthy control volunteers. Morphologic cerebral changes were assessed using voxel-based morphometry. Student t test statistical maps of functional and morphologic differences between patients and controls were obtained using a general linear model. RESULTS: In TLE patients, [(18)F]fluoro-l-dopa uptake was reduced to the same extent in caudate and putamen in both cerebral hemispheres as well as in the substantia nigra (SN). These dopaminergic functional alterations occurred without any glucose metabolism changes in these areas. The only mild morphologic abnormality was found in striatal regions without any changes in the SN. CONCLUSION: The present study provides support for dopaminergic neurotransmission involvement in temporal lobe epilepsy. The discrepancies between gray matter volume atrophy and the pattern of [(18)F]fluoro-l-dopa suggest that basal ganglia involvement is not related to structural subcortical abnormalities. A functional decrease can be ruled out because there was no change of the glycolytic pathway metabolism in these areas.

A hybrid scatter correction for 3D PET based on an estimation of the distribution of unscattered coincidences: implementation on the ECAT EXACT HR+.

We implemented a hybrid scatter-correction method for 3D PET that combines two scatter-correction methods in a complementary way. The implemented scheme uses a method based on the discrimination of the energy of events (the estimation of trues method (ETM)) and an auxiliary method (the single scatter simulation method (SSSI) or the convolution-subtraction method (CONV)) in an attempt to increase the accuracy of the correction over a wider range of acquisitions. The ETM takes into account the scatter from outside the field-of-view (FOV), which is not estimated with the auxiliary method. On the other hand, the auxiliary method accounts for events that have scattered with small angles, which have an energy that cannot be discriminated from that of unscattered events using the ETM. The ETM uses the data acquired in an upper energy window above the photopeak (550-650 keV) to obtain a noisy estimate of the unscattered events in the standard window (350-650 keV). Our implementation uses the auxiliary method to correct the residual scatter in the upper window. After appropriate scaling, the upper window data are subtracted from the total coincidences acquired in the standard window, resulting in the final scatter estimate, after smoothing. In this work we compare the hybrid method with the corrections used by default in the 2D and 3D modes of the ECAT EXACT HR+ using phantom measurements. Generally, the contrast was better with the hybrid method, although the relative errors of quantification were similar. We conclude that hybrid techniques such as the one implemented in this work can provide an accurate, general-purpose and practical way to correct the scatter in 3D PET, taking into account the scatter from outside the FOV.

Iterative crystal efficiency calculation in fully 3-D PET.

The calculation of the intrinsic efficiency of individual crystals is one of the steps needed to obtain accurate images of the radioisotope distribution in positron emission tomography (PET). These efficiencies can be computed by comparing the number of coincidence counts obtained when the crystals are equally illuminated by the same source. However, because the number of coincidence counts acquired for one crystal also depends on the efficiency of the other crystals in coincidence, most methods of crystal efficiency calculation need to assume that the influence of the other crystals is negligible. If there are large crystal efficiency variations, this approximation may lead to systematic errors. We have recently implemented an iterative method for a single ring of detectors that does not rely on this assumption. In this paper, we describe a fully three-dimensional (3-D) iterative method that better exploits the sensitivity of the tomograph and allows reduced acquisition times or the use of narrow energy windows. We compare the performance of the iterative method (single-ring and extended to fully 3-D) with noniterative techniques for different acquisition times of a uniform cylinder. Two different energy windows were used to assess the performance of each method with different levels of variations of crystal efficiency. The results showed that the iterative methods are more accurate when large efficiency variations exist and that only the fully 3-D methods provided good efficiency estimates with very low duration scans. We, thus, conclude that iterative fully 3-D methods provide the best estimations and can be used in a larger range of situations than can the other methods tested.

Comparison of clinical data sets acquired on different tomographs using 6-18F-L-dopa.

Longitudinal positron emission tomography (PET) studies of 6-18F-L-dopa uptake in the striatum are used to assess the progression of Parkinson's disease or the survival of neuronal cells grafted in parkinsonian patients. These studies are performed over several years, and data analysis may suffer from the change from old tomographs to new machines with better sensitivity and spatial resolution. Furthermore, such studies on parkinsonian patients may be accomplished in either 2D or 3D acquisition mode. The aforementioned improvements offer great benefits for the study of neurodegenerative diseases, especially those affecting the striatum. However, direct comparison of data is not straightforward owing to variation in scanner characteristics. In this study, we assessed the feasibility of comparing the 6-18F-L-dopa striatal uptake values (Kc) measured in two groups of healthy subjects using two tomographs of different generations. We re-studied and compared acquisitions performed on 14 healthy subjects using 6-18F-L-dopa. Half of these studies had been performed in 2D acquisition mode using an ECAT 953B. The other half had been performed in 3D acquisition mode using an ECAT EXACT HR+. Different reconstruction protocols were used and the Kc values obtained were statistically compared. The results showed that lowering the transverse spatial resolution of images obtained with the scanner having the better spatial resolution, so that it more closely matched that of the other machine, allowed similar KC values to be obtained in healthy subjects. This study shows that quantitative results of 6-18F-L-dopa scans can be matched between different scanners with different intrinsic resolutions. This can be accomplished using adequate modifications of the reconstruction parameters. Such modifications can be used to help in the longitudinal monitoring of parkinsonian patients using different tomographs.

Comparison of fluorine-18 and bromine-76 imaging in positron emission tomography.

State of the art positron emission tomography (PET) systems allow for scatter and attenuation correction. However, the size of the structure being studied and the region of interest (ROI) chosen also influence the accuracy of measurements of radioactive concentration. Furthermore, the limited spatial resolution of PET tomographs, which depends, among other factors, on the range of positrons in matter, can also contribute to a loss in quantitation accuracy. In this paper we address the influence of positron range, structure size and ROI size on the quantitation of radioactive concentration using PET. ECAT EXACT HR+ (HR+) and ECAT 953B/31 (ECAT 953B) PET systems were used in phantom acquisitions performed with two radioisotopes with different positron ranges. The 3D Hoffman phantom was scanned on both scanners with both radioisotopes, to visually analyse the image quality. A resolution phantom having six spheres of different diameters in a Plexiglas cylinder was used to calculate the values of the contrast recovery coefficient or hot spot recovery coefficient and of the spill-over or cold spot recovery coefficient under different imaging conditions used in clinical routine at our institution. Activity ratios were varied between 2 and 30 or between 0.4 and 200 by filling the spheres with fluorine-18 or bromine-76 respectively and the cylinder with 11C. Dynamic scans were performed on each scanner. Data were reconstructed using the same parameters as are used in clinical protocols. The variations in sphere and cylinder activities with time were fitted using the function M(t)=k1. A(t)+k2.B(t), where M(t) is the radioactivity concentration measured in an ROI placed on each sphere and A(t) and B(t) represent the true radioactivity concentrations present at time t in the spheres and in the cylinder respectively. k1 and k2 are factors representing the contrast recovery coefficient and the spill-over from surrounding activity on measurements respectively. The visual analysis of images obtained using a 3D Hoffman phantom showed that image resolution and image contrast between different regions are radioisotope dependent and clearly better when using 18F. Linear profiles taken on these images confirmed the visual assessment. For a given scanner, the k1 values obtained with 18F were systematically higher than those measured using 76Br in the same machine (especially for the smaller spheres) when using the same ROI. For a sphere of a particular diameter, the use of a wider ROI resulted in lower quantitative accuracy when using the same isotope and the same camera. Lower quantitative accuracy was found for smaller spheres for all ROI sizes used in image analysis. For the same scanner and for a similar imaging situation (same sphere and same ROI), it was found that k1 and k2 values depend on the radioisotope used. For the same isotope and tomograph, the k1 values obtained decreased with the size of the structures imaged, as well as with the increase in ROI size. The use of a tomograph with better spatial resolution (HR+, rather than ECAT 953B) greatly increased the k1 values for 18F while only a mild improvement in these values was observed for 76Br. The use of 76Br led to k2 values that were slightly higher than those measured using 18F. These differences may have been due to the difference in the range of the positrons emitted by the radioisotopes used in this study. The measurements performed in this study show that the comparison of studies obtained on the same camera depends on the radioisotope used and may require the adaptation of ROI size between examinations. Marked differences are visible if the positron ranges of such radioisotopes are very different. Therefore, when employing commercially available tomographs and imaging protocols used in clinical routine, the effects of differences in positron range on image quality and quantitation are noticeable and correction for these effects may be of importance. (ABSTRACT TRUNCATED)

Validation of the three-dimensional acquisition mode in positron emission tomography for the quantitation of [18F]fluoro-DOPA uptake in the human striata.

Three-dimensional (3D) positron emission tomography (PET) is attractive for [18F]fluoro-DOPA studies, since the sensitivity improvement is maximal for radioactive sources located in central planes, which is usually the case for the human striata. However, the image quantitation in that mode must be assessed because of the nearly threefold increase in scattered coincidences. We report the results of [18F]fluoro-DOPA studies performed on six normal volunteers. Each one was scanned in the 3D and two-dimensional (2D) modes on the same tomograph. The quantitation in the 3D and 2D modes was compared for a Patlak graphical analysis with the occipital counts as the input function (Ki) and a striatooccipital ratio analysis. We find that, in 3D PET, a scatter correction is required to preserve the same quantitation as in 2D PET. When the 3D data sets are corrected for scatter, the quantitation of the [18F]fluoro-DOPA uptake, using the Patlak analysis, is similar in the 2D and 3D acquisition modes. Conversely, analysis of the striatooccipital ratio leads to higher values in 3D PET because of a better in-plane resolution. Finally, using the 3D mode, the dose injected to the subjects can be reduced by a factor greater than 1.5 without any loss in accuracy compared to the 2D mode.

Count rate performances of TTVO3: the CEA-LETI time-of-flight positron emission tomograph.

The authors present the count rate performance of the CEA-LETI TTVO3 time-of-flight positron emission tomography (PET) system using both physical measurements and H(2)(15)O bolus human myocardial studies. They also present a comparison between the counting statistics of H(2)(15)O brain studies performed on this machine and on the latest available high-resolution brain bismuth germanate (BGO) tomograph, the ECAT 953B/31. During the 80 mCi cerebral blood flow study, the count rate reached 100 K events/s, and the same experiment performed on a high-resolution BGO brain machine gave only a 30% increase in signal. These results demonstrate that TTVO3 is particularly suitable for H(2)(15)O flow studies.

Physical characteristics of the ECAT 953B/31: a new high resolution brain positron tomograph.

A high spatial resolution brain positron tomograph, the ECAT 953B/31, is presented. The machine consists of two 76.5 cm diameter rings (patient port diameter: 36 cm) made of 24 8x8 BGO detector blocks each, each block being coupled to four 1 in(2) Hammamatsu phototubes. The machine has 15 9 cmx1 mm motorized removable septa, which allows reconstruction of 31 slices 3.375 mm apart. The transaxial resolution (FWHM) in the reconstructed image (with wobbling) is 4.5 mm at center, 5.2 mm (tangential) and 5.6 mm at 10 cm from center. With septa out of the field of view (FOV), the axial resolution degrades to 5.5 mm a center and 6.3 mm at 10 cm from center. At 1 muCi/cc with a 250 keV threshold and a 12 ns coincidence window, the sensitivity is 146100 true events, the ratio of randoms to trues is 0.10, the scatter fraction is 17% and the dead-time losses are 30%. With septa out of the FOV, the sensitivity is increased by a factor 3.6, while the scatter fraction reaches 0.9. Images obtained with (18 )F-DG and H(2)(15)O in human brains and (18 )F-DOPA in a baboon brain demonstrate that the ECAT 953B/31 will be suitable for high resolution and for low count rate brain studies.

Some physical characteristics of a time-of-flight positron tomography (CEA-LETI-TTV03) obtained with the EEC emission phantom.

We present measurements performed on the time-of-flight positron emission tomograph CEA-LETI-TTV03 with the EEC Emission Phantom. The transaxial resolution for a direct plane in the reconstructed image (Ramp filter, fc = 0.25 mm-1) was found to be 6.2 mm (radial and tangential) at center, 6.8 mm (radial) and 6.1 mm (tangential) at 45 mm from the center and 8.6 (radial) and 5.3 (tangential) mm at 90 mm from the center; in an image reconstructed with a Hanning filter at the same frequency cut-off and with a scatter correction, these values are degraded to 7.1 mm (tangential) and 7.2 mm (radial) at center, 7.6 mm (radial) and 6.9 mm (radial) at 45 mm from the center and 9.5 mm (radial) and 6.1 mm (tangential) at 90 mm from the center. Values were identical for direct and cross planes and correcting from the scatter radiation did not modify the resolution. Recovery coefficients for a 17 cm diameter sphere were equal to 0.85 in a direct plane and 1. for a cross plane, this being due to the axial resolution which is 9.1 mm and 7.1 mm at 5.5 cm from the center for direct and cross planes respectively. With 10 mCi in the phantom simulating abdominal imaging the maximum recorded coincidences on a cross plane was 84.4 kevents/sec, 50.2 kevents/sec on a direct plane and 343.4 kevents/sec for the entire machine. The dead time losses in terms of trues were equal to 24% and 17% for direct and cross planes respectively while the single rate was 19900/sec/detector. Scatter fraction, evaluated using a uniform cylinder, was found to be 15% for a cross plane.