Alessandro Passeri

Long-term ambulatory enterogastric reflux monitoring. Validation of a new fiberoptic technique.

A new technique for the long-term ambulatory detection of enterogastric and nonacid gastroesophageal reflux has been conceived, developed, and validated. It is based on the use of a fiberoptic sensor that utilizes the optical properties of bile.In vitro studies have shown good precision, good stability, sensitivity of 2.5 μmol/liter bilirubin concentration, as well as a useful working range of 2.5–100 μmol/liter bilirubin concentration.In vivo studies have been performed in 29 subjects. Simultaneous gastric aspirations have allowed a comparison of fiberoptic system measurements both with spectrophotometric analysis and bile acid concentrations of corresponding gastric juice samples. Linear correlations were shown between fiberoptic assessment and both spectrophotometric and bile acid concentration findings (P<0.01). Simultaneous assessment of reflux with the fiberoptic system and cholescintigraphy has shown a 92.9% concordance as regards the presence or absence of reflux. Present results imply that the fiberoptic system is an important tool for the understanding of the clinical relevance of enterogastric and nonacid gastroesophageal reflux.

Compensation of spatial system response in SPECT with conjugate gradient reconstruction technique

A procedure for the determination of the system matrix in single photon emission tomography (SPECT) is described which uses the conjugate gradient reconstruction technique in order to take into account the variable system resolution of a camera equipped with parallel-hole collimators. The procedure involves the acquisition of the system line spread functions (LSF) in the region occupied by the object to be studied. Those data are used to generate a set of weighting factors based on the assumption that the LSFs of the collimated camera are of Gaussian shape with the full width at half maximum (FWHM) linearly dependent on the source depth in the span of image space. The factors are stored on a disc file for subsequent use in the reconstruction process. Afterwards the reconstruction is performed using the conjugate gradient method with the system matrix modified by the incorporation of these precalculated factors in order to take into account the variable geometrical system response. The set of weighting factors is regenerated whenever the acquisition conditions are changed (collimator, radius of rotation). In the case of an ultra high resolution (UHR) collimator 2000 weighting factors need to be calculated. The modification of the system matrix for the geometrical response allows the number of iterations to increase, considerably improving image definition without the appearance of noise artifacts. Moreover, phantom studies show that the number of iterations is less critical because of improved stability in the convergence to the solution. For brain studies of patients 10-15 iterations are usually performed. Studies with a single line source give a value between 7 and 8 mm for the FWHM of the point spread function (PSF) when the conjugate gradient method with modified system matrix is used on data acquired with a UHR collimator, whereas without the modification of the system matrix the result is 9 mm FWHM, if filtered backprojection (FBP) is used with the same filter as in the clinical studies the result is 15 mm FWHM. The results of this work show that proper definition of the system matrix using conjugate gradients influences the quality of the reconstruction remarkably. Nevertheless, further work has to be done in order to assess to what extent the system matrix is ill-conditioned and, eventually, to define a suitable regularization technique.

Clinical use of quantitative cardiac perfusion PET: rationale, modalities and possible indications. Position paper of the Cardiovascular Committee of the European Association of Nuclear Medicine (EANM)

Until recently, PET was regarded as a luxurious way of performing myocardial perfusion scintigraphy, with excellent image quality and diagnostic capabilities that hardly justified the additional cost and procedural effort. Quantitative perfusion PET was considered a major improvement over standard qualitative imaging, because it allows the measurement of parameters not otherwise available, but for many years its use was confined to academic and research settings. In recent years, however, several factors have contributed to the renewal of interest in quantitative perfusion PET, which has become a much more readily accessible technique due to progress in hardware and the availability of dedicated and user-friendly platforms and programs. In spite of this evolution and of the growing evidence that quantitative perfusion PET can play a role in the clinical setting, there are not yet clear indications for its clinical use. Therefore, the Cardiovascular Committee of the European Association of Nuclear Medicine, starting from the experience of its members, decided to examine the current literature on quantitative perfusion PET to (1) evaluate the rationale for its clinical use, (2) identify the main methodological requirements, (3) identify the remaining technical difficulties, (4) define the most reliable interpretation criteria, and finally (5) tentatively delineate currently acceptable and possibly appropriate clinical indications. The present position paper must be considered as a starting point aiming to promote a wider use of quantitative perfusion PET and to encourage the conception and execution of the studies needed to definitely establish its role in clinical practice.

Physical modelling (geometrical system response, Compton scattering and attenuation) in brain SPECT using the conjugate gradients reconstruction method

A technique for the simultaneous compensation of spatial system response, Compton scattering and attenuation in brain SPECT using 99Tcm is described here. The procedure involves the acquisition of experimental information relative to spatial response, attenuation and scatter from capillary sources as well as by means of a special experimental set-up. The latter has been accurately designed to isolate the Compton scattering part of the point spread function, by blocking the acquisition of primary gamma rays. The formulation of a physical model allowed a set of weighting factors, which were stored in a disk file, to be calculated. Data were then reconstructed by means of the conjugate gradients iterative least-squares technique, with the system matrix modified by the incorporation of the precalculated weighting factors. Experimental projection data relative to phantoms with constant activity along the rotation axis as well as experimental projection data relative to one phantom with variable axial activity, were acquired. Reconstruction of these data shows that a high degree of compensation for attenuation and scatter in brain SPECT is achieved. With respect to the reconstruction algorithms based upon the backprojection of analytically filtered experimental projections, higher spatial resolution together with very good quantitative activity ratios are the main accomplishments of this reconstruction technique. The method has also been applied to in vivo study reconstructions.

A PPAR-gamma agonist attenuates pulmonary injury induced by irradiation in a murine model.

PURPOSE/OBJECTIVE(S) Due to its anti-inflammatory, antifibrotic and antineoplastic properties, the PPAR-γ agonist rosiglitazone is of interest in the prevention and therapy of radiation-induced pulmonary injury. We evaluated the radioprotective effects of rosiglitazone in a murine model of pulmonary damage to determine whether radioprotection was selective for normal and tumor tissues. METHODS Lungs in C57BL/6J mice were irradiated (19 Gy) with or without rosiglitazone (RGZ, 5mg/kg/day for 16 weeks, oral gavage). Computed tomography (CT) was performed and Hounsfield Units (HU) were determined during the observation period. Histological analysis and evaluation of fibrosis/inflammatory markers by western blot were performed at 16 weeks. A549 tumor-bearing CD1 mice were irradiated (16 Gy) with or without RGZ, and tumor volumes were measured at 35 days. RESULTS Rosiglitazone reduced radiologic and histologic signs of fibrosis, inflammatory infiltrate, alterations to alveolar structures, and HU lung density that was increased due to irradiation. RGZ treatment also significantly decreased Col1, NF-kB and TGF-β expression and increased Bcl-2 protein expression compared to the irradiation group and reduced A549 clonogenic survival and xenograft tumor growth. CONCLUSIONS Rosiglitazone exerted a protective effect on normal tissues in radiation-induced pulmonary injury, while irradiated lung cancer cells were not protected in vivo and in vitro. Thus, rosiglitazone could be proposed as a radioprotective agent in the treatment of lung cancer.

High-performance computing and networking as tools for accurate emission computed tomography reconstruction.

It is well known that the quantitative potential of emission computed tomography (ECT) relies on the ability to compensate for resolution, attenuation and scatter effects. Reconstruction algorithms which are able to take these effects into account are highly demanding in terms of computing resources. The reported work aimed to investigate the use of a parallel high-performance computing platform for ECT reconstruction taking into account an accurate model of the acquisition of single-photon emission tomographic (SPET) data. An iterative algorithm with an accurate model of the variable system response was ported on the MIMD (Multiple Instruction Multiple Data) parallel architecture of a 64-node Cray T3D massively parallel computer. The system was organized to make it easily accessible even from low-cost PC-based workstations through standard TCP/IP networking. A complete brain study of 30 (64×64) slices could be reconstructed from a set of 90 (64×64) projections with ten iterations of the conjugate gradients algorithm in 9 s, corresponding to an actual speed-up factor of 135. This work demonstrated the possibility of exploiting remote high-performance computing and networking resources from hospital sites by means of low-cost workstations using standard communication protocols without particular problems for routine use. The achievable speed-up factors allow the assessment of the clinical benefit of advanced reconstruction techniques which require a heavy computational burden for the compensation effects such as variable spatial resolution, scatter and attenuation. The possibility of using the same software on the same hardware platform with data acquired in different laboratories with various kinds of SPET instrumentation is appealing for software quality control and for the evaluation of the clinical impact of the reconstruction methods.

Is 16-frame really superior to 8-frame gated SPECT for the assessment of left ventricular volumes and ejection fraction? Comparison of two simultaneously acquired gated SPECT studies

PurposeConflicting data exist about the difference between 8- and 16-frame gated single-photon emission computed tomography (SPECT) left ventricular volumes and ejection fraction (EF); moreover, the influence of framing on detection of stress-induced functional changes is unknown.MethodsIn 133 patients, two separate gated SPECT studies, one with 8 and one with 16 frames, were simultaneously acquired during a single gantry orbit using dedicated software. In 33 of 133 patients, two additional studies (with 8 and 16 frames, respectively) were acquired using arrhythmia rejection. Left ventricular EF and volumes were calculated using the QGS software. Stress-induced ischemia was identified on summed perfusion images.ResultsArrhythmia-rejection did not influence volumes and EF independently of framing rate. Using data without arrhythmia-rejection, there was a significant difference in volumes and EF between 8 and 16 frames both in resting and post-stress gated SPECT. However, the difference was small: 2.6% for resting and 2.8% for post-stress EF. Both using 8 and 16 frames, there were significantly larger volumes and lower EF in patients with than without stress-induced ischemia. A stress-induced decrease >5 EF units was observed in 26 of 133 patients using 8 and in 23 of 133 using 16 frames, respectively, with finding agreement in 19 patients.ConclusionsComparing two simultaneously acquired studies, the use of 16 instead of 8 frames has minor and predictable influence on functional data. Furthermore, there are no differences in the detection of stress-induced functional changes. The advantage of 16 over 8 frames in the daily clinical practice appears questionable.

A brain phantom for studying contrast recovery in emission computerized tomography

A brain phantom is described that is characterized by a high anatomical definition and by the possibility of varying the internal contrast with the use of a single radioactive solution. The experimental work was done with a single-photon emission computerized tomographic (SPET) rotating camera. The phantom was used to study the contrast recovery of both the filtered back-projection and an iterative reconstruction algorithm. Moreover, it was also used to find a cross-calibration factor between activity concentrations in the SPET slices and an external reference.

Radiosynthesis and micro-SPECT analysis of triazole-based RGD integrin ligands as non-peptide molecular imaging probes for angiogenesis

Taking advantage of click chemistry, we synthesized triazole-containing RGD peptidomimetics capable of binding to αvβ3 integrin with diverse potency, and selected (125)I-labeled compounds proved to interact in vitro and in vivo with αvβ3 integrin expressed by melanoma cells. Two (125)I-compounds containing either 2-aminobenzimidazole or 2-aminopyridine groups as the arginine bioisostere with the capacity to selectively bind cells of highly expressing αvβ3 melanoma xenografts were found using micro-SPECT imaging studies.

Myocardial blood flow and left ventricular functional reserve in hypertrophic cardiomyopathy: a 13NH3 gated PET study

IntroductionIschemia in hypertrophic cardiomyopathy (HCM) is caused by coronary microvascular dysfunction (CMD), which is detected by measuring myocardial blood flow (MBF) with PET. Whether CMD may be associated with ischemic left ventricular (LV) dysfunction is unclear. We therefore assessed LV ejection fraction (EF) reserve in HCM patients undergoing dipyridamole (Dip) PET.MethodsResting and stress 13NH3 dynamic as well as gated PET were performed in 34 HCM patients. Segmental MBF and transmural perfusion gradient (TPG = subendocardial / subepicardial MBF) were assessed. LVEF reserve was considered abnormal if Dip LVEF decreased more than 5 units as compared to rest.ResultsEighteen patients had preserved (group A) and 16 abnormal LVEF reserve (group B; range −7 to −32). Group B patients had greater wall thickness than group A, but resting volumes, LVEF, resting and Dip MBF, and myocardial flow reserve were similar. Group B had slightly higher summed stress score and summed difference score in visual analysis than group A, and a significantly higher summed stress wall motion score. In group B, resting TPG was slightly lower (1.31 ± 0.29 vs. 1.37 ± 0.34, p <0.05), and further decreased after Dip, whilst in group A it increased (B = 1.20 ± 0.39, p < 0.0001 vs. rest and vs. A = 1.40 ± 0.43). The number of segments per patient with TPG <1 was higher than in group A (p < 0.001) and was a significant predictor of impaired LVEF reserve (OR 1.86, p < 0.02), together with wall thickness (OR 1.3, p < 0.02).ConclusionAbnormal LVEF response is common in HCM patients following Dip, and is related to abnormal TPG, suggesting that subendocardial ischemia might occur under Dip and cause transient LV dysfunction. Although in vivo this effect may be hindered by the adrenergic drive associated with effort, these findings may have relevance in understanding exercise limitation and heart failure symptoms in HCM.