Ines Dominguez-Prado

Impact of time-of-flight and point-spread-function in SUV quantification for oncological PET.

Background Accuracy in the quantification of the SUV is a critical point in PET because proper quantification of tumor uptake is essential for therapy monitoring and prognosis evaluation. Recent advances such as time-of-flight (TOF) and point-spread-function (PSF) reconstructions have dramatically improved detectability. However, first experiences with these techniques have shown a consistent tendency to measure markedly high SUV values, bewildering nuclear medicine physicians and referring clinicians. Purpose We investigated different reconstruction and quantification procedures to determine the optimum protocol for an accurate SUV quantification in last generation PET scanners. Methods Both phantom and patient images were evaluated. A complete set of experiments was performed using a body phantom containing 6 spheres with different background levels and contrasts. Whole-body FDG PET/CT of 20 patients with breast and lung cancer was evaluated. One hundred five foci were identified by 2 experienced nuclear medicine physicians. Each acquisition was reconstructed both with classical and advanced (TOF, PSF) reconstruction techniques. Each sphere and each in vivo lesion was quantified with different parameters as follows: SUVmax, SUVmean, and SUV50 (mean within a 50% isocontour). Results This study has confirmed that quantification with SUVmax produces important overestimation of metabolism in new generation PET scanners. This is a relevant result because, currently, SUVmax is the standard parameter for quantification. SUV50 has been shown as the best alternative, especially when applied to images reconstructed with PSF + TOF. Conclusions SUV50 provides accurate quantification and should replace SUVmax in PET tomographs incorporating advanced reconstruction techniques. PSF + TOF reconstruction is the optimum for both detection and accurate quantification.

Voxel-Based Analysis of Dual-Time-Point 18F-FDG PET Images for Brain Tumor Identification and Delineation

We have investigated dual-time-point 18F-FDG PET for the detection and delineation of high-grade brain tumors using quantitative criteria applied on a voxel basis. Methods: Twenty-five patients with suspected high-grade brain tumors and inconclusive MRI findings underwent 11C-methionine PET and dual-time-point 18F-FDG PET. Images from each subject were registered and spatially normalized. Parametric maps of standardized uptake value (SUV) and tumor–to–normal gray matter (TN) ratio for each PET image were obtained. Tumor diagnosis was evaluated according to 4 criteria comparing standard and delayed 18F-FDG PET images: any SUV increase, SUV increase greater than 10%, any TN increase, and TN increase greater than 10%. Voxel-based analysis sensitivity was assessed using 11C-methionine as a reference and compared with visual and volume-of-interest analysis for dual-time-point PET images. Additionally, volumetric assessment of the tumor extent that fulfills each criterion was compared with the volume defined for 11C-methionine PET. Results: The greatest sensitivity for tumor identification was obtained with any increase of TN ratio (100%), followed by a TN increase greater than 10% (96%), any SUV increase (80%), and an SUV increase greater than 10% (60%). These values were superior to visual analysis of standard 18F-FDG (sensitivity, 40%) and delayed 18F-FDG PET (sensitivity, 52%). Volume-of-interest analysis of dual-time-point PET reached a sensitivity of only 64% using the TN increase criterion. Regarding volumetry, voxel-based analysis with the TN ratio increase as a criterion, compared with 11C-methionine PET, detected 55.4% of the tumor volume, with the other criteria detecting volumes lower than 20%. Nevertheless, volume detection presented great variability, being better for metastasis (78%) and glioblastomas (56%) than for anaplastic tumors (12%). A positive correlation was observed between the volume detected and the time of acquisition of the delayed PET image (r = 0.66, P < 0.001), showing volumes greater than 75% when the delayed image was obtained at least 6 h after 18F-FDG injection. Conclusion: Compared with standard 18F-FDG PET studies, quantitative dual-time-point 18F-FDG PET can improve sensitivity for the identification and volume delineation of high-grade brain tumors.

PET Tracers for Clinical Imaging of Breast Cancer.

Molecular imaging of breast cancer has undoubtedly permitted a substantial development of the overall diagnostic accuracy of this malignancy in the last years. Accurate tumour staging, design of individually suited therapies, response evaluation, early detection of recurrence and distant lesions have also evolved in parallel with the development of novel molecular imaging approaches. In this context, positron emission tomography (PET) can be probably seen as the most interesting molecular imaging technology with straightforward clinical application for such purposes. Dozens of radiotracers for PET imaging of breast cancer have been tested in laboratory animals. However, in this review we shall focus mainly in the smaller group of PET radiopharmaceuticals that have lead through into the clinical setting. PET imaging can be used to target general metabolic phenomena related to tumoural transformation, including glucose metabolism and cell proliferation, but can also be directed to specific hormone receptors that are characteristic of the breast cancer cell. Many other receptors and transport molecules present in the tumour cells could also be of interest for imaging. Furthermore, molecules related with the tumour microenvironment, tumour induced angiogenesis or even hypoxia could also be used as molecular biomarkers for breast cancer imaging.

PET optimization for improved assessment and accurate quantification of 90Y-microsphere biodistribution after radioembolization

PURPOSE 90Y-microspheres are widely used for the radioembolization of metastatic liver cancer or hepatocellular carcinoma and there is a growing interest for imaging 90Y-microspheres with PET. The aim of this study is to evaluate the performance of a current generation PET/CT scanner for 90Y imaging and to optimize the PET protocol to improve the assessment and the quantification of 90Y-microsphere biodistribution after radioembolization. METHODS Data were acquired on a Biograph mCT-TrueV scanner with time of flight (TOF) and point spread function (PSF) modeling. Spatial resolution was measured with a 90Y point source. Sensitivity was evaluated using the NEMA 70 cm line source filled with 90Y. To evaluate the count rate performance, 90Y vials with activity ranging from 3.64 to 0.035 GBq were measured in the center of the field of view (CFOV). The energy spectrum was evaluated. Image quality with different reconstructions was studied using the Jaszczak phantom containing six hollow spheres (diameters: 31.3, 28.1, 21.8, 16.1, 13.3, and 10.5 mm), filled with a 207 kBq/ml 90Y concentration and a 5:1 sphere-to-background ratio. Acquisition time was adjusted to simulate the quality of a realistic clinical PET acquisition of a patient treated with SIR-Spheres®. The developed methodology was applied to ten patients after SIR-Spheres® treatment acquiring a 10 min per bed PET. RESULTS The energy spectrum showed the 90Y bremsstrahlung radiation. The 90Y transverse resolution, with filtered backprojection reconstruction, was 4.5 mm in the CFOV and degraded to 5.0 mm at 10 cm off-axis. 90Y absolute sensitivity was 0.40 kcps/MBq in the center of the field of view. Tendency of true and random rates as a function of the 90Y activity could be accurately described using linear and quadratic models, respectively. Phantom studies demonstrated that, due to low count statistics in 90Y PET acquisition, the optimal parameters for the standard OSEM+PSF reconstruction were only one iteration and a postreconstruction filter of 6 mm FWHM, for both TOF and non-TOF reconstructions. Moreover, when TOF is included, the signal to noise ratio increased and visibility achieved 100% by the experienced observers and 93.3% according to the Rose model of statistical detection. In 50% of patients, TOF allowed the visualization of 90Y radioembolized lesions not seen without TOF, confirming phantom results. Liver activity was accurately quantified, with no significant differences between reconstructed and actual delivered activity to the whole-liver [mean relative difference (10.2±14.7)%]. CONCLUSIONS Qualitative and quantitative 90Y PET imaging improved with the introduction of TOF in a PET/CT scanner, thereby allowing the visualization of microsphere deposition in lesions not visible in non-TOF images. This technique accurately quantifies the total activity delivered to the liver during radioembolization with (90)Y-microspheres and allows dose estimation.

Metabolic patterns in prion diseases: an FDG PET voxel-based analysis

PurposeClinical diagnosis of human prion diseases can be challenging since symptoms are common to other disorders associated with rapidly progressive dementia. In this context, 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) might be a useful complementary tool. The aim of this study was to determine the metabolic pattern in human prion diseases, particularly sporadic Creutzfeldt-Jakob disease (sCJD), the new variant of Creutzfeldt-Jakob disease (vCJD) and fatal familial insomnia (FFI).MethodsWe retrospectively studied 17 patients with a definitive, probable or possible prion disease who underwent FDG PET in our institution. Of these patients, 12 were diagnosed as sCJD (9 definitive, 2 probable and 1 possible), 1 was diagnosed as definitive vCJD and 4 were diagnosed as definitive FFI. The hypometabolic pattern of each individual and comparisons across the groups of subjects (control subjects, sCJD and FFI) were evaluated using a voxel-based analysis.ResultsThe sCJD group exhibited a pattern of hypometabolism that affected both subcortical (bilateral caudate, thalamus) and cortical (frontal cortex) structures, while the FFI group only presented a slight hypometabolism in the thalamus. Individual analysis demonstrated a considerable variability of metabolic patterns among patients, with the thalamus and basal ganglia the most frequently affected areas, combined in some cases with frontal and temporal hypometabolism.ConclusionPatients with a prion disease exhibit a characteristic pattern of brain metabolism presentation in FDG PET imaging. Consequently, in patients with rapidly progressive cognitive impairment, the detection of these patterns in the FDG PET study could orient the diagnosis to a prion disease.

Simulated FDG-PET studies for the assessment of SUV quantification methods

AIM To study in detail the accuracy and repeatability of three commonly used methods for SUV estimation in solitary pulmonary nodules. MATERIAL AND METHODS We have designed a realistic framework based on simulated FDG-PET acquisitions from an anthropomorphic activity model that included solitary pulmonary nodules (different sizes) of well-known SUV. This framework enables us to compare the SUV values obtained from the reconstructed PET images with the real SUV values. Three commonly used methods (SUVmax, SUVmean and SUV50) were used to estimate the tumor activity. RESULTS Our results showed the tumor activity was overestimated using SUVmax and clearly subestimated using SUVmean. Instead, the quantification of SUV50 showed great agreement with the simulated tumor activity and only slight subestimation was found for very small lesions. On the other hand, SUVmean showed better performance than SUV50 in terms of repeatability, providing variabilities below 5% for all tumor sizes and for injected doses as low as 111 MBq. CONCLUSIONS Our findings showed that SUV50 provided better performance for estimating accurately tumor SUV values in pulmonary nodules, but SUVmean showed better results in terms of repeatability.

Aportación del tiempo de vuelo y de la modelización de la respuesta a una fuente puntual a las características de funcionamiento del tomógrafo PET/TAC Biograph mCT

OBJECTIVE To characterize the performance of the Biograph mCT PET/CT TrueV scanner with time of flight (TOF) and point spread function (PSF) modeling. MATERIAL AND METHODS The PET/CT scanner combines a 64-slice CT and PET scanner that incorporates in the reconstruction the TOF and PSF information. PET operating characteristics were evaluated according to the standard NEMA NU 2-2007, expanding some tests. In addition, different reconstruction algorithms were included, and the intrinsic radiation and tomographic uniformity were also evaluated. RESULTS The spatial resolution (FWHM) at 1 and 10cm was 4.4 and 5.3mm, improving to 2.6 and 2.5mm when PSF is introduced. Sensitivity was 10.9 and 10.2 Kcps/MBq at 0 and 10cm from the axis. Scatter fraction was less than 34% at low concentrations and the noise equivalent count rate (NECR) was maximal at 27.8 kBq/mL with 182 Kcps, the intrinsic radiation produced a rate of 4.42 true coincidences per second. Coefficient of variation of the volume and system uniformity were 4.7 and 0.8% respectively. The image quality test showed better results when PSF and TOF were included together. PSF improved the hot spheres contrast and background variability, while TOF improved the cold spheres contrast. CONCLUSIONS The Biograph mCT TrueV scanner has good performance characteristics. The image quality improves when the information from the PSF and the TOF is incorporated in the reconstruction.

Whole body 18fluoro-l-dopa PET–CT: a useful tool for location and surgical guidance in primary carcinoid tumours

Neuroendocrine tumours (NETs) represent a diagnostic and therapeutic challenge. Primary tumour is not localised in 20% to 50% of NETs, midgut carcinoids being particularly elusive [1]. 18Fluoro-L-dopa has emerged as a new imaging tool for NETs diagnosis with improved tumour detection and staging compared with conventional imaging (SRS and/or CT) [2, 3]. We present a patient with metastatic carcinoid tumour who underwent PET–CT scan with 18fluoro-L-dopa, which was of key importance to locate the primary tumour and guide its surgical resection. An 18-year-old woman with a 1-year history of progressive facial episodic flushing presented an elevated serotonin serum level and mild elevation of 5-OH-IAA. MRI showed multiple small hypervascular liver lesions, and US-guided liver biopsy revealed a metastatic carcinoid tumour. Imaging tests including thoracic and abdominal CT, SRS with 111-In-octreotide and 18FDG PET–CT, and gastric and colon endoscopies showed no evidence of primary tumour. Because gastroenteropancreatic NETs are known to uptake and decarboxylate L-dopa [4], PET–CT using 18fluoro-L-dopa was carried out. In addition to multiple bilobar liver metastases (SUVmax=15), this study demonstrated three hypermetabolic peritoneal foci: two located at the height of the fifth lumbar vertebra (SUVmax=16.4) (a, b) and a third smaller focus below the others with lower uptake (SUVmax=4) apparently located in the bowel (c).

Texture analysis of high-resolution dedicated breast 18 F-FDG PET images correlates with immunohistochemical factors and subtype of breast cancer

PurposeThis study aims to determine whether PET textural features measured with a new dedicated breast PET scanner reflect biological characteristics of breast tumors.MethodsOne hundred and thirty-nine breast tumors from 127 consecutive patients were included in this analysis. All of them underwent a 18F-FDG PET scan before treatment. Well-known PET quantitative parameters such as SUVmax, SUVmean, metabolically active tumor volume (MATV) and total lesion glycolysis (TLG) were extracted. Together with these parameters, local, regional, and global heterogeneity descriptors, which included five textural features (TF), were computed. Immunohistochemical classification of breast cancer considered five subtypes: luminal A like (LA), luminal B like/HER2 − (LB −), luminal B like/HER2+ (LB+), HER2-positive-non-luminal (HER2pnl), and triple negative (TN). Associations between PET features and tumor characteristics were assessed using non-parametric hypothesis tests.ResultsAlong with well-established associations, new correlations were found. HER2-positive tumors had significantly higher uptake (p < 0.001, AUCs > 0.70) and presented different global and regional heterogeneity (p = 0.002, p = 0.016, respectively, AUCs < 0.70). Nine out of ten analyzed features were significantly associated with immunohistochemical subtype. Uptake was lower for LA tumors (p < 0.001) with AUCs ranging from 0.71 to 0.88 for each subgroup comparison. Heterogeneity metrics were significantly associated when comparing LA and LB − (p < 0.01), being regional heterogeneity metrics more discriminative than any other parameter (AUC = 0.80 compared to AUC = 0.71 for SUV). LB+ and HER2pnl tumors also showed more regional heterogeneity than LA tumors (AUCs = 0.79 and 0.84, respectively). After comparison with whole-body PET studies, we observed an overall improvement in the classification ability of both non-heterogeneity metrics and textural features.ConclusionsPET parameters extracted from high-resolution dedicated breast PET images showed new and stronger correlations with immunohistochemical factors and immunohistochemical subtype of breast cancer compared to whole-body PET.

Radioembolization: Concepts and Procedures

Radioembolization (RE) is a form of intravascular brachytherapy that consists in delivering implantable radioactive microspheres into the arteries that feed liver tumors in order to provide a high dose of radiation to tumor nodules irrespective of their number, size, and location, while preserving the non-tumoral liver tissue from receiving a harmful level of radiation. The nature of the procedure using Yttrium-90 RE (Y-90 RE) requires the collaboration of a multidisciplinary team including hepatologists or oncologists, interventional radiologists and nuclear medicine specialists working together in close collaboration. To avoid toxicity, a thorough angiographic evaluation is performed to identify every extrahepatic vessel that may feed the tumors (to assure efficiency), accomplished with Tc-99m labeled macroaggregated albumin (Tc-MAA) injection into the vessel of interest, in order to mimic the microsphere application during the treatment. Both procedures combined are essential to plan the radioembolization (RE) therapy and to detect any occult arteriovenous shunt from the hepatic arterial system to the pulmonary or gastrointestinal venous systems and so identify potentially to calculate the degree of hepatopulmonary shunting, and to detect and eventually occlude every collateral vessel that arising from a hepatic artery may carry microspheres to the GI tract or other extrahepatic organs. With all this information, the treatment is designed and activity is calculated in order to maximize the dose of radiation delivered to liver tumors while safely preserving the non-tumoral parenchyma.