Performance evaluation of a preclinical SPECT/CT system for multi-animal and multi-isotope quantitative experiments.

The aim was to study the performance of the U-SPECT6/CT E-class system for preclinical imaging, to later demonstrate the viability of simultaneous multi-animal and multi-isotope imaging with reliable quantitative accuracy. The performance of the SPECT was evaluated for two collimators dedicated for mouse (UHS-M) and rat imaging (UHR-RM) in terms of sensitivity, energy resolution, uniformity and spatial resolution. Point sources, hot­rod and uniform phantoms were scanned, and additional tests were carried out to evaluate singular settings such as simultaneous multi-isotope acquisition and imaging with a multi-bed system. For in-vivo evaluation, simultaneous triple-isotope and multi-animal studies were performed on mice. Sensitivity for 99mTc was 2370 cps/MBq for the UHS-M collimator and 493 cps/MBq for the UHR-RM. Rods of 0.6 mm and 0.9 mm were discernible with the UHS-M and UHR-RM collimators respectively, with optimized reconstruction. Uniformity in low counting conditions has proven to be poor (> 75%). Multi-isotope and multi-bed phantom acquisitions demonstrated accurate quantification. In mice, simultaneous multi-isotope imaging provided the separate distribution of 3 tracers and image quality of the multi-mouse bone scan was adequate. The U-SPECT6/CT E-class has shown good sensitivity and spatial resolution. This system provides quantitative images with suitable image quality for multi-mouse and multi-isotope acquisitions.

Early Imaging and Molecular Changes with Neoadjuvant Bevacizumab in Stage II/III Breast Cancer.

This prospective, phase II study evaluated novel biomarkers as predictors of response to bevacizumab in patients with breast cancer (BC), using serial imaging methods and gene expression analysis. Patients with primary stage II/III BC received bevacizumab 15 mg/kg (cycle 1; C1), then four cycles of neoadjuvant docetaxel doxorubicin, and bevacizumab every 3 weeks (C2-C5). Tumour proliferation and hypoxic status were evaluated using 18F-fluoro-3'-deoxy-3'-L-fluorothymidine (FLT)- and 18F-fluoromisonidazole (FMISO)-positron emission tomography (PET) at baseline, and during C1 and C5. Pre- and post-bevacizumab vascular changes were evaluated using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Molecular biomarkers were assessed using microarray analysis. A total of 70 patients were assessed for treatment efficacy. Significant decreases from baseline in tumour proliferation (FLT-PET), vascularity, and perfusion (DCE-MRI) were observed during C1 (p ≤ 0.001), independent of tumour subtype. Bevacizumab treatment did not affect hypoxic tumour status (FMISO-PET). Significant changes in the expression of 28 genes were observed after C1. Changes in vascular endothelial growth factor receptor (VEGFR)-2p levels were observed in 65 patients, with a > 20% decrease in VEGFR-2p observed in 13/65. Serial imaging techniques and molecular gene profiling identified several potentially predictive biomarkers that may predict response to neoadjuvant bevacizumab therapy in BC patients.

Ultra-low dose whole-body CT for attenuation correction in a dual tracer PET/CT protocol for multiple myeloma.

PURPOSE: To investigate within phantoms the minimum CT dose allowed for accurate attenuation correction of PET data and to quantify the effective dose reduction when a CT for this purpose is incorporated in the clinical setting. METHODS: The NEMA image quality phantom was scanned within a large parallelepiped container. Twenty-one different CT images were acquired to correct attenuation of PET raw data. Radiation dose and image quality were evaluated. Thirty-one patients with proven multiple myeloma who underwent a dual tracer PET/CT scan were retrospectively reviewed. 18F-fluorodeoxyglucose PET/CT included a diagnostic whole-body low dose CT (WBLDCT: 120 kV-80mAs) and 11C-Methionine PET/CT included a whole-body ultra-low dose CT (WBULDCT) for attenuation correction (100 kV-40mAs). Effective dose and image quality were analysed. RESULTS: Only the two lowest radiation dose conditions (80 kV-20mAs and 80 kV-10mAs) produced artifacts in CT images that degraded corrected PET images. For all the other conditions (CTDIvol ≥ 0.43 mGy), PET contrast recovery coefficients varied less than ± 1.2%. Patients received a median dose of 6.4 mSv from diagnostic CT and 2.1 mSv from the attenuation correction CT. Despite the worse image quality of this CT, 94.8% of bone lesions were identifiable. CONCLUSION: Phantom experiments showed that an ultra-low dose CT can be implemented in PET/CT procedures without any noticeable degradation in the attenuation corrected PET scan. The replacement of the standard CT for this ultra-low dose CT in clinical PET/CT scans involves a significant radiation dose reduction.

Impact of the dosimetry approach on the resulting 90Y radioembolization planned absorbed doses based on 99mTc-MAA SPECT-CT: is there agreement between dosimetry methods?

BACKGROUND: Prior radioembolization, a simulation using 99mTc-macroaggregated albumin as 90Y-microspheres surrogate is performed. Gamma scintigraphy images (planar, SPECT, or SPECT-CT) are acquired to evaluate intrahepatic 90Y-microspheres distribution and detect possible extrahepatic and lung shunting. These images may be used for pre-treatment dosimetry evaluation to calculate the 90Y activity that would get an optimal tumor response while sparing healthy tissues. Several dosimetry methods are available, but there is still no consensus on the best methodology to calculate absorbed doses. The goal of this study was to retrospectively evaluate the impact of using different dosimetry approaches on the resulting 90Y-radioembolization pre-treatment absorbed dose evaluation based on 99mTc-MAA images. METHODS: Absorbed doses within volumes of interest resulting from partition model (PM) and 3D voxel dosimetry methods (3D-VDM) (dose-point kernel convolution and local deposition method) were evaluated. Additionally, a new "Multi-tumor Partition Model" (MTPM) was developed. The differences among dosimetry approaches were evaluated in terms of mean absorbed dose and dose volume histograms within the volumes of interest. RESULTS: Differences in mean absorbed dose among dosimetry methods are higher in tumor volumes than in non-tumoral ones. The differences between MTPM and both 3D-VDM were substantially lower than those observed between PM and any 3D-VDM. A poor correlation and concordance were found between PM and the other studied dosimetry approaches. DVH obtained from either 3D-VDM are pretty similar in both healthy liver and individual tumors. Although no relevant global differences, in terms of absorbed dose in Gy, between both 3D-VDM were found, important voxel-by-voxel differences have been observed. CONCLUSIONS: Significant differences among the studied dosimetry approaches for 90Y-radioembolization treatments exist. Differences do not yield a substantial impact in treatment planning for healthy tissue but they do for tumoral liver. An individual segmentation and evaluation of the tumors is essential. In patients with multiple tumors, the application of PM is not optimal and the 3D-VDM or the new MTPM are suggested instead. If a 3D-VDM method is not available, MTPM is the best option. Furthermore, both 3D-VDM approaches may be indistinctly used.

El especialista en Radiofísica Hospitalaria en el Servicio de Medicina Nuclear / Specialists in Hospital Radiophysics in the Department of Nuclear Medicine

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Image quality evaluation in a modern PET system: impact of new reconstructions methods and a radiomics approach.

The present work investigates the influence of different biological and physical parameters on image quality (IQ) perception of the abdominal area in a modern PET scanner, using new reconstruction algorithms and testing the utility of a radiomics approach. Scans of 112 patients were retrospectively included. Images were reconstructed using both OSEM + PSF and BSRM methods, and IQ of the abdominal region was subjectively evaluated. First, 22 IQ related parameters were obtained (including count rate and biological or mixed parameters) and compared to the subjective IQ scores by means of correlations and logistic regression. Second, an additional set of radiomics features was extracted, and a model was constructed by means of an elastic-net regression. For the OSEM + PSF and especially for the BSRM reconstructions, IQ parameters presented only at best moderated correlations with the subjective IQ. None of the studied parameters presented a good predictive power for IQ, while a simple radiomics model increased the performance of the IQ prediction. These results suggest the necessity of changing the standard parameters to evaluate IQ, particularly when a BSRM algorithm is involved. Furthermore, it seems that a simple radiomics model can outperform the use of any single parameter to assess IQ.

Phantom, clinical, and texture indices evaluation and optimization of a penalized-likelihood image reconstruction method (Q.Clear) on a BGO PET/CT scanner.

INTRODUCTION: The aim of this study was to evaluate the behavior of a penalized-likelihood image reconstruction method (Q.Clear) under different count statistics and lesion-to-background ratios (LBR) on a BGO scanner, in order to obtain an optimum penalization factor (ß value) to study and optimize for different acquisition protocols and clinical goals. METHODS: Both phantom and patient images were evaluated. Data from an image quality phantom were acquired using different Lesion-to-Background ratios and acquisition times. Then, each series of the phantom was reconstructed using ß values between 50 and 500, at intervals of 50. Hot and cold contrasts were obtained, as well as background variability and contrast-to-noise ratio (CNR). Fifteen 18 F-FDG patients (five brain scans and 10 torso acquisitions) were acquired and reconstructed using the same ß values as in the phantom reconstructions. From each lesion in the torso acquisition, noise, contrast, and signal-to-noise ratio (SNR) were computed. Image quality was assessed by two different nuclear medicine physicians. Additionally, the behaviors of 12 different textural indices were studied over 20 different lesions. RESULTS: Q.Clear quantification and optimization in patient studies depends on the activity concentration as well as on the lesion size. In the studied range, an increase on ß is translated in a decrease in lesion contrast and noise. The net product is an overall increase in the SNR, presenting a tendency to a steady value similar to the CNR in phantom data. As the activity concentration or the sphere size increase the optimal ß increases, similar results are obtained from clinical data. From the subjective quality assessment, the optimal ß value for torso scans is in a range between 300 and 400, and from 100 to 200 for brain scans. For the recommended torso ß values, texture indices present coefficients of variation below 10%. CONCLUSIONS: Our phantom and patients demonstrate that improvement of CNR and SNR of Q.Clear algorithm which depends on the studied conditions and the penalization factor. Using the Q.Clear reconstruction algorithm in a BGO scanner, a ß value of 350 and 200 appears to be the optimal value for 18F-FDG oncology and brain PET/CT, respectively.

Significant dose reduction is feasible in FDG PET/CT protocols without compromising diagnostic quality.

PURPOSE: To reduce the radiation dose to patients by optimizing oncological FDG PET/CT protocols. METHODS: The baseline PET/CT protocol in our institution for oncological PET/CT examinations consisted of the administration of 5.18 MBq/kg of FDG and a CT acquisition with a reference current-time product of 120 mAs. In 2016, FDG activity was reduced to 4.44 and 3.70 MBq/kg and reference CT current-time-product was reduced to 100 and 80 mAs. 322 patients scanned with different protocols were retrospectively evaluated. For each patient, effective dose was calculated. The overall image quality was subjectively rated by the referring physician on a 4-point scale (IQ score: 1 excellent, 2 good, 3 poor but interpretable, 4 poor not interpretable). Image quality was quantitatively evaluated measuring noise in the liver. RESULTS: CT Results: Effective dose was progressively reduced from 9.5 ±â€¯2.8 to 8.0 ±â€¯2.3 and 6.2 ±â€¯1.5 mSv (p < 0.001). A mean dose reduction of 34.9% was achieved. There was a significant degradation of IQ score (p < 0.05) and noise (p < 0.001). Nevertheless, the number of poor quality studies (IQ score >2) did not increase. PET Results: Effective dose was gradually reduced from 6.5 ±â€¯1.4 to 5.7 ±â€¯1.3 and 5.0 ±â€¯1.0 mSv (p < 0.001). Average dose reduction was 23.4%. IQ score (p < 0.05) and noise (p < 0.001) significantly degraded for lower activity protocols. However, all images with reduced activity were scored as interpretable (IQ score ≤ 3). CONCLUSIONS: A significant radiation dose reduction of 28.7% was reached. Despite a slight reduction in image quality, the new regime was successfully implemented with readers reporting unchanged clinical confidence.

Effective dose estimation for oncological and neurological PET/CT procedures.

BACKGROUND: The aim of this study was to retrospectively evaluate the patient effective dose (ED) for different PET/CT procedures performed with a variety of PET radiopharmaceutical compounds. PET/CT studies of 210 patients were reviewed including Torso (n = 123), Whole body (WB) (n = 36), Head and Neck Tumor (HNT) (n = 10), and Brain (n = 41) protocols with 18FDG (n = 170), 11C-CHOL (n = 10), 18FDOPA (n = 10), 11C-MET (n = 10), and 18F-florbetapir (n = 10). ED was calculated using conversion factors applied to the radiotracer activity and to the CT dose-length product. RESULTS: Total ED (mean ± SD) for Torso-11C-CHOL, Torso-18FDG, WB-18FDG, and HNT-18FDG protocols were 13.5 ± 2.2, 16.5 ± 4.5, 20.0 ± 5.6, and 15.4 ± 2.8 mSv, respectively, where CT represented 77, 62, 69, and 63% of the protocol ED, respectively. For 18FDG, 18FDOPA, 11C-MET, and 18F-florbetapir brain PET/CT studies, ED values (mean ± SD) were 6.4 ± 0.6, 4.6 ± 0.4, 5.2 ± 0.5, and 9.1 ± 0.4 mSv, respectively, and the corresponding CT contributions were 11, 14, 23, and 26%, respectively. In 18FDG PET/CT, variations in scan length and arm position produced significant differences in CT ED (p < 0.01). For dual-time-point imaging, the CT ED (mean ± SD) for the delayed scan was 3.8 ± 1.5 mSv. CONCLUSIONS: The mean ED for body and brain PET/CT protocols with different radiopharmaceuticals ranged between 4.6 and 20.0 mSv. The major contributor to total ED for body protocols is CT, whereas for brain studies, it is the PET radiopharmaceutical.

Performance Characteristics of the Whole-Body Discovery IQ PET/CT System.

The aim of this study was to assess the physical performance of a new PET/CT system, the Discovery IQ with 5-ring detector blocks. Methods: Performance was measured using the National Electrical Manufacturers Association NU2-2012 methodology. Image quality was extended by accounting for different acquisition parameters (lesion-to-background ratios [8:1, 4:1, and 2:1] and acquisition times) and reconstruction algorithms (VUE-point HD [VPHD], VPHD with point-spread-function modeling [VPHD-S], and Q.Clear). Tomographic reconstruction was also assessed using a Jaszczak phantom. Additionally, 30 patient lesions were analyzed to account for differences in lesion volume and SUV quantification between reconstruction algorithms. Results: Spatial resolution ranged from 4.2 mm at 1 cm to 8.5 mm at 20 cm. Sensitivity measured at the center and at 10 cm was 22.8 and 20.4 kps/kBq, respectively. The noise-equivalent counting rate peak was 124 kcps at 9.1 kBq/cm3 The scatter fraction was 36.2%. The accuracy of correction for count losses and randoms was 3.9%. In the image quality test, contrast recovery for VPHD, VPHD-S, and Q.Clear ranged from 18%, 18%, and 13%, respectively (hot contrast; 10-mm sphere diameter; ratio, 2:1), to 68%, 67%, and 81%, respectively (cold contrast; 37-mm sphere diameter; ratio, 8:1). Background variability ranged from 3.4%, 3.0%, and 2.1%, respectively (ratio, 2:1), to 5.5%, 4.8%, and 3.7%, respectively (ratio, 8:1). On Q.Clear reconstruction, the decrease in the penalty term (ß) increased the contrast recovery coefficients and background variability. With the Jaszczak phantom, image quality increased overall when a reconstruction algorithm modeling the point-spread function was used, and use of Q.Clear increased the signal-to-noise ratio. Lesions analyzed using VPHD-S and Q.Clear had an SUVmean of 6.5 ± 3 and 7 ± 3, respectively (P < 0.01), and an SUVmax of 11 ± 4.8 and 12 ± 4, respectively (P < 0.01). No significant difference in mean lesion volume was found between algorithms. Conclusion: Among the various Discovery bismuth germanium oxide-based PET/CT scanners, the IQ with 5-ring detector blocks has the highest overall performance, with improved sensitivity and counting rate performance. Q.Clear reconstruction improves the PET image quality, with higher recovery coefficients and lower background variability.

Lessons from 11C-dihydrotetrabenazine imaging in a xenograft mouse model of rat insulinoma: is PET imaging of pancreatic beta cell mass feasible?

BACKGROUND: The feasibility of beta cell mass (BCM) imaging and quantification with positron emission tomography (PET) in the pancreas is controversial. In an effort to shed some light on this topic, we have used a xenograft model of rat insulinoma (RIN) in mice, mimicking an intramuscular islet transplantation situation. METHODS: A total of 105 RIN cells were subcutaneously implanted in nude mice (N.=8). Tumor size and glycaemia levels were determined daily. Rat C-peptide was measured to demonstrate rat insulin production. PET imaging with 11C-(+)-α-dihydrotetrabenazine (11C-DTBZ) was done at 3 and 4 weeks and compared with 18F-FDG and 18F-DOPA studies in the same mice. Ex-vivo autoradiography with 11C-DTBZ was carried out in frozen sections of tumors. VMAT2 expression was measured by Western-blot and immunohistochemistry in tumors and RIN cells. RESULTS: Functional rat insulin production in mice was demonstrated by substantial decrease in glycaemia (<50 mg/dL by week 4) and rat C-peptide levels (7.2±2.6 ng/mL) similar to those measured in control rats. PET studies showed that tumor imaging with 11C-DTBZ at four (N.=8) and five (N.=5) weeks was negative; only bigger tumors could be seen with 18F-DOPA. In explanted tumors 11C-DTBZ autoradiography was negative, albeit VMAT2 expression measured by Western-blot and immunohistochemistry was lower than in cultured RIN cells. CONCLUSIONS: Although insulinomas are fully functional it does not seem feasible to use 11C-DTBZ for in-vivo measuring of BCM. This might either be due to inherent technical limitations of PET, decrease in VMAT2 expression in the tumors due to unknown reasons, or other biological limiting facts.

Brain PET imaging optimization with time of flight and point spread function modelling.

PURPOSE: To assess the influence of reconstruction algorithms and parameters on the PET image quality of brain phantoms in order to optimize reconstruction for clinical PET brain studies in a new generation PET/CT. METHODS: The 3D Hoffman phantom that simulates (18)F-fluorodeoxyglucose (FDG) distribution was imaged in a Siemens Biograph mCT TrueV PET/CT with Time of Flight (TOF) and Point Spread Function (PSF) modelling. Contrast-to-Noise Ratio (CNR), contrast and noise were studied for different reconstruction models: OSEM, OSEM + TOF, OSEM + PSF and OSEM + PSF + TOF. The 2D multi-compartment Hoffman phantom was filled to simulate 4 different tracers' spatial distribution: FDG, (11)C-flumazenil (FMZ), (11)C-Methionine (MET) and 6-(18)F-fluoro-l-dopa (FDOPA). The best algorithm for each tracer was selected by visual inspection. The maximization of CNR determined the optimal parameters for each reconstruction. RESULTS: In the 3D Hoffman phantom, both noise and contrast increased with increasing number of iterations and decreased with increasing FWHM. OSEM + PSF + TOF reconstruction was generally superior to other reconstruction models. Visual analysis of the 2D Hoffman brain phantom suggested that OSEM + PSF + TOF is the optimum algorithm for tracers with focal uptake, such as MET or FDOPA, and OSEM + TOF for tracers with diffuse cortical uptake (i.e. FDG and FMZ). Optimization of CNR demonstrated that OSEM + TOF reconstruction must be performed with 2 iterations and a filter FWHM of 3 mm, and OSEM + PSF + TOF reconstruction with 4 iterations and 1 mm FWHM filter. CONCLUSIONS: Optimization of reconstruction algorithm and parameters has been performed to take particular advantage of the last generation PET scanner, recommending specific settings for different brain PET radiotracers.

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.

A method for multichannel dosimetry with EBT3 radiochromic films.

PURPOSE: An improved method for multichannel dosimetry is presented. This method explicitly takes into account the information provided by the unexposed image of the film. METHODS: The method calculates the dose by applying a couple of perturbations to the scanned dose, one dependent and the other independent on the color channel. The method has been compared with previous multichannel and two single channel methods (red and green) against measurements using two different tests: first, five percentage depth dose profiles covering a wide range of doses; second, the dose map perpendicular to the beam axis for a 15 × 15 cm(2) square field. Finally, the results of 30 IMRT quality assurances tests are presented. All tests have been evaluated using the gamma analysis. RESULTS: The coefficient of variation was found to be similar for all methods in a wide range of doses. The results of the proposed method are more in agreement with the experimental measurements and with the treatment planning system. Furthermore, the differences in the mean gamma pass rates are statistically significant. CONCLUSIONS: The improved multichannel dosimetric method is able to remove many of the common disturbances usually present in radiochromic films and improves the gamma analysis results compared with the other three methods.

Application of spherical diodes for megavoltage photon beams dosimetry.

PURPOSE: External beam radiation therapy (EBRT) usually uses heterogeneous dose distributions in a given volume. Designing detectors for quality control of these treatments is still a developing subject. The size of the detectors should be small to enhance spatial resolution and ensure low perturbation of the beam. A high uniformity in angular response is also a very important feature in a detector, because it has to measure radiation coming from all the directions of the space. It is also convenient that detectors are inexpensive and robust, especially to perform in vivo measurements. The purpose of this work is to introduce a new detector for measuring megavoltage photon beams and to assess its performance to measure relative dose in EBRT. METHODS: The detector studied in this work was designed as a spherical photodiode (1.8 mm in diameter). The change in response of the spherical diodes is measured regarding the angle of incidence, cumulated irradiation, and instantaneous dose rate (or dose per pulse). Additionally, total scatter factors for large and small fields (between 1 × 1 cm(2) and 20 × 20 cm(2)) are evaluated and compared with the results obtained from some commercially available ionization chambers and planar diodes. Additionally, the over-response to low energy scattered photons in large fields is investigated using a shielding layer. RESULTS: The spherical diode studied in this work produces a high signal (150 nC/Gy for photons of nominal energy of 15 MV and 160 for 6 MV, after 12 kGy) and its angular dependence is lower than that of planar diodes: less than 5% between maximum and minimum in all directions, and 2% around one of the axis. It also has a moderated variation with accumulated dose (about 1.5%/kGy for 15 MV photons and 0.7%/kGy for 6 MV, after 12 kGy) and a low variation with dose per pulse (± 0.4%), and its behavior is similar to commercial diodes in total scatter factor measurements. CONCLUSIONS: The measurements of relative dose using the spherical diode described in this work show its feasibility for the dosimetry of megavoltage photon beams. A particularly important feature is its good angular response in the MV range. They would be good candidates for in vivo dosimetry, and quality assurance of VMAT and tomotherapy, and other modalities with beams irradiating from multiple orientations, such as Cyberknife and ViewRay, with minor modifications.

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: SUV(max), SUV(mean), and SUV(50) (mean within a 50% isocontour). RESULTS: This study has confirmed that quantification with SUV(max) produces important overestimation of metabolism in new generation PET scanners. This is a relevant result because, currently, SUV(max) is the standard parameter for quantification. SUV(50) has been shown as the best alternative, especially when applied to images reconstructed with PSF + TOF. CONCLUSIONS: SUV(50) provides accurate quantification and should replace SUV(max) in PET tomographs incorporating advanced reconstruction techniques. PSF + TOF reconstruction is the optimum for both detection and accurate quantification.

Decreased carbon-11-flumazenil binding in early Alzheimer's disease.

Neuronal loss in Alzheimer's disease, a better correlate of cognitive impairment than amyloid deposition, is currently gauged by the degree of regional atrophy. However, functional markers, such as GABA(A) receptor density, a marker of neuronal integrity, could be more sensitive. In post-mortem hippocampus, GABA(A) messenger RNA expression is reduced even in mild cognitive impairment. We measured whole-brain GABA(A) binding potential in vivo using [(11)C]-flumazenil positron emission tomography and compared GABA(A) binding with metabolic and volumetric measurements. For this purpose, we studied 12 subjects, six patients with early Alzheimer's disease and six healthy controls, with [(11)C]-flumazenil and [(18)F]-fluorodeoxyglucose positron emission tomography, as well as with high-resolution magnetic resonance imaging. Data were evaluated with both voxel-based parametric methods and volume of interest methods. We found that in early Alzheimer's disease, with voxel-based analysis, [(11)C]-flumazenil binding was decreased in infero-medial temporal cortex, retrosplenial cortex and posterior perisylvian regions. Inter-group differences reached corrected significance when using an arterial input function. Metabolism measured with positron emission tomography and volumetric measurements obtained with magnetic resonance imaging showed changes in regions affected in early Alzheimer's disease, but, unlike with [(11)C]-flumazenil binding and probably due to sample size, the voxel-based findings failed to reach corrected significance in any region of the brain. With volume of interest analysis, hippocampi and posterior cingulate gyrus showed decreased [(11)C]-flumazenil binding. In addition, [(11)C]-flumazenil hippocampal binding correlated with memory performance. Remarkably, [(11)C]-flumazenil binding was decreased precisely in the regions showing the greatest degree of neuronal loss in post-mortem studies of early Alzheimer's disease. From these data, we conclude that [(11)C]-flumazenil binding could be a useful marker of neuronal loss in early Alzheimer's disease.

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.