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R Di Paola

Publications and source records attributed to R Di Paola.

At least 19 recordsLinked to original sources

Evidence for genetic epistasis in human insulin resistance: the combined effect of PC-1 (K121Q) and PPARgamma2 (P12A) polymorphisms.

Insulin resistance is believed to be under the control of several genes often interacting each other. However, whether genetic epistasis does in fact modulate human insulin sensitivity is unknown. In 338 healthy unrelated subjects from Sicily, all nondiabetic and not morbidly obese, we investigated whether two gene polymorphisms previously associated with insulin resistance (namely PC-1 K121Q and PPARgamma2 P12A) affect insulin sensitivity by interacting. PC-1 X121Q subjects showed higher level of fasting glucose, lower insulin sensitivity (by both the Matsuda insulin sensitivity index and M values at clamp, the latter performed in a subgroup of 113 subjects representative of the overall cohort) and higher insulin levels during the oral glucose tolerance test (OGTT) than PC-1 K121K subjects. In contrast, no difference in any of the measured variables was observed between PPARgamma2 P12P and X12A individuals. The deleterious effect of the PC-1 X121Q genotype on each of these three variables was significant and entirely dependent upon the coexistence of the PPARgamma2 P12P genotype. Among PPARgamma2 P12P carriers also fasting insulin and glucose levels during OGTT were higher in PC-1 X121Q than in K121K individuals. In contrast, no deleterious effect of the PC-1 X121Q genotype was observed among PPARgamma2 X12A carriers; rather, in these subjects a lower body mass index and consequently lower fasting insulin level was observed in PC-1 X121Q than in K121K carriers. Overall, a significant interaction between the two genes was observed on body mass index, insulin levels (both fasting and after OGTT) and both insulin sensitivity (i.e., insulin sensitivity index and M value) and insulin secretion (i.e., HOMA-B%) indexes.

Adult↗

Role of inflammation in the secondary injury following experimental spinal cord trauma.

AIM: The primary traumatic mechanical injury to the spinal cord causes the death of a number of neurons that cannot be recovered, neither regenerated. However, neurons continue to die for hours after spinal cord injury (SCI), and this represents a potentially avoidable event. One of mechanisms that have been touted to contribute importantly to the evolution of such secondary cell death is the local inflammatory response in the injured spinal cord. In this report we have used an in vivo model to induce acute SCI and reproduce the acute pathological events associated with inflammation after traumatic SCI in rats. METHODS: Twenty-two adult male Sprague-Dawley rats were used in the study. SCI was produced by extradural clip compression at T5-T9 level. The rats spinal cord was analysed at 1 hour to measure the malonildialdehyde (MDA) levels considered an index of lipid peroxidation. At 4 hours were measured the levels of myeloperoxidase (MPO) activity considered as the index of leukocytes activity. Finally the spinal cord was extracted 12 hours after the trauma to measure the cytoplasmatic levels of IkB-a considered as the index of activity of the transcriptional factor nuclear factor-kB (NF-kB). RESULTS: After the SCI, both the levels of MDA and MPO were significantly higher compared with naive and sham-operated rats (p=0.01). Western blotting analysis demonstrated the disappearance of IkB-alpha in the cytoplasm indicating nuclear translocation of the NF-kB. CONCLUSION: The study confirms the role of inflammation in contributing to the secondary injury after experimental SCI in the rat.

Animals↗

Insulin modulates PC-1 processing and recruitment in cultured human cells.

We evaluated whether insulin signaling modulates plasma cell glycoprotein (PC-1) plasma membrane recruitment, posttranslational processing, and gene expression in human cultured cell lines. Insulin induced a fourfold increase (P < 0.01) of membrane PC-1 expression by rapid and sensitive mechanism(s). This effect was reduced (P < 0.05-0.01) by inhibition of phosphatidylinositol 3-kinase (200 nmol/l wortmannin) and S6 kinase (50 nmol/l rapamycin) activities and intracellular trafficking (50 micromol/l monensin) and was not accompanied by PC-1 gene expression changes. Moreover, at Western blot, insulin elicited the appearance, in both plasma membrane and cytosol, of a PC-1-related 146-kDa band (in addition to bands of 163, 117, 106, and 97 kDa observed also in absence of insulin) that was sensitive to endoglycosidase H. Finally, inhibition of PC-1 translocation to plasma membrane, by wortmannin pretreatment, increases insulin-stimulated receptor autophosphorylation. Our data indicate that insulin stimulates PC-1 posttranslational processing and translocation to the plasma membrane, which in turn impairs insulin receptor signaling. Bidirectional cross talk between insulin and PC-1, therefore, takes place, which may be part of the hormone self-desensitization mechanism.

Androstadienes↗

The tyrosine kinase inhibitor tyrphostin AG 126 reduces the multiple organ failure induced by zymosan in the rat.

OBJECTIVE: To investigate the effects of tyrphostin AG 126, a tyrosine kinase inhibitor, on the multiple organ failure (MOF) caused by zymosan in the rat. DESIGN: Zymosan (500 mg/kg, suspended in saline solution, i.p.) causes an enhanced formation of reactive oxygen species, which contribute to the pathophysiology of MOF. After zymosan or saline administration, animals were monitored for 12 days. MEASUREMENTS AND RESULTS: Treatment of rats with tyrphostin AG 126 (10 mg/kg, 3 mg/kg or 1 mg/kg intraperitoneally, 1 h and 6 h after zymosan) attenuated the peritoneal exudation and the migration of polymorphonuclear cells caused by zymosan in a dose-dependent fashion. Tyrphostin AG 126 also attenuated the lung, liver, and intestinal injury (histology) as well as the increase in the levels of myeloperoxidase and malondialdehyde caused by zymosan in the lung, liver, and intestine. Immunohistochemical analysis for nitrotyrosine, poly (ADP-ribose) polymerase (PAR), iNOS, and COX-2 revealed a positive staining in lung, liver and intestine from zymosan-treated rats. The degree of staining for nitrotyrosine, PAR, iNOS, and COX-2 were markedly reduced in tissue sections obtained from zymosan-treated rats which had received tyrphostin AG 126. Furthermore, treatment of rats with tyrphostin AG 126 significantly reduced the production of peroxynitrite and of pro-inflammatory cytokines TNF-alpha and IL-1beta. CONCLUSIONS: This study provides the first evidence that the protein kinase inhibitor tyrphostin AG 126 attenuates the degree of MOF associated with zymosan-induced peritonitis in the rat.

Animals↗

Benzydamine: an alternative nonsteroidal anti-inflammatory drug in patients with nimesulide-induced urticaria.

BACKGROUND: Cutaneous adverse reactions to nonsteroidal anti-inflammatory drugs (NSAIDs), in particular urticaria/angiedema syndrome, represent a frequent problem in clinical practice. To date laboratory tests for the diagnosis of these adverse reactions are not available. A patient with an adverse drug reaction to NSAIDs needs an alternative drug to assume if necessary. Nimesulide is a highly prescribed nonsteroidal anti-inflammatory drug (NSAID) world-wide. It is also described as one of the most tolerated NSAID. In this paper we present data on the tolerability of benzydamine in nimesulide-sensitive patients. PATIENTS AND METHODS: One hundred and thirty-seven patients with nimesulide-induced urticaria were submitted to a single-blind, placebo-controlled peroral challenge with increasing doses of benzydamine. RESULTS: One hundred and thirty-four out of 137 (98%) patients tolerated benzydamine without adverse effects, only three (2%) experienced immediate systemic urticaria (1 at the first dose and 2 at the second dose). CONCLUSION: Benzydamine is a well tolerated drug in patients with nimesulide-induced urticaria and it may represent a valid alternative NSAID in nimesulide-sensitive patients.

Acetaminophen↗

Second generation antihistamines in the treatment of seasonal allergic rhinitis due to Parietaria and cypress pollen.

Second generation antihistamines have been employed in the treatment of seasonal allergic rhinitis for many years. However, their effects on two distinctive Mediterranean allergic conditions, viz. Parietaria pollinosis and cypress pollinosis, have been scarcely investigated, so far. A comparative efficacy and side effect trial of astemizole and terfenadine in the treatment of seasonal allergic rhinitis due to either Parietaria or cypress pollen was carried out in 27 adult patients, according to a double-blind, double-dummy parallel-group design. Airborne pollen monitoring allowed comparison of symptom scores with pollen counts. Seven patients (26%) withdrew, due to poor symptom control. In contrast, in a subset of 15 patients who completed the trial, treatment led to a substantial and statistically significant decline in symptom severity in both the astemizole and the terfenadine study group. However, no statistically significant inter-group differences could be detected.

Adult↗

Importance of the choice of the collimator for the detection of small lesions in scintimammography: a phantom study.

99mTc methoxyisobutylisonitrile planar scintimammography (SMM) is mostly performed using low-energy high-resolution (LEHR) parallel collimators. We studied whether using a different collimator could improve the detection of small (< 1.5 cm) lesions for which SMM sensitivity is poor. Thirty four breast phantom configurations were considered, either with hot spheres simulating lesions or without any spheres. For each configuration, four planar acquisitions were performed using LEHR, low-energy ultra high-resolution (LEUHR), high-resolution fan-beam (HRFB) and ultra high-resolution fan-beam (UHRFB) collimators. Images corresponding to the 20% and 10% energy windows and to the Jaszczak subtraction were calculated. A database including 156 borderline images was derived. After training, 10 observers scored the images for the presence of a sphere. The performances in sphere detection were studied using receiver operating characteristic (ROC) analysis. For all types of image, the area under the ROC curve was highest with the UHRFB collimator and lowest with either the LEUHR or the HRFB collimator. For the 10% energy window images conventionally used in SMM, the detection sensitivities averaged 91%, 73%, 60% and 55% for the UHRFB, LEHR, HRFB and LEUHR collimators respectively, for the same specificity of 64%. We conclude that detection of small tumours in planar SMM might be significantly improved by using a UHRFB collimator instead of an LEHR collimator.

Breast Neoplasms↗

The Q121 PC-1 variant and obesity have additive and independent effects in causing insulin resistance.

PC-1 is a membrane glycoprotein that impairs insulin receptor function. Its K121Q polymorphism is a genetic determinant of insulin resistance. We investigated whether the PC-1 gene modulates insulin sensitivity independently of weight status (i.e. both in nonobese and obese individuals). Nondiabetic subjects [164 males, 267 females; age, 37 +/- 0.6 yr, mean +/- SEM; body mass index (BMI), 32.7 +/- 0.5 kg/m(2)], who were subdivided into 220 nonobese (BMI < or = 29.9) and 211 obese, were studied. Although subjects were nondiabetic by selection criteria, plasma insulin concentrations during oral glucose tolerance test were higher (P < 0.05) in Q allele-carrying subjects (K121Q or Q121Q genotypes), compared with K121K individuals, in both the nonobese and obese groups. Insulin sensitivity, measured by euglycemic clamp in a representative subgroup of 131 of 431 randomly selected subjects, progressively decreased (P < 0.001) from nonobese K121K [n = 61; glucose disposal (M) = 34.9 +/- 1.1 micromol/kg/min] to nonobese Q (n = 21; M = 29.9 +/- 2.0), obese K121K (n = 31, M = 18.5 +/- 1.2), and obese Q (n = 18, M = 15.5 +/- 1.2) carriers. The K121Q polymorphism was correlated with insulin sensitivity independently (P < 0.05) of BMI, gender, age, and waist circumference. In conclusion, the Q121 PC-1 variant and obesity have independent and additive effects in causing insulin resistance.

Adolescent↗

The Q allele variant (GLN121) of membrane glycoprotein PC-1 interacts with the insulin receptor and inhibits insulin signaling more effectively than the common K allele variant (LYS121).

When overexpressed, the membrane glycoprotein PC-1 may play a role in human insulin resistance through the inhibition of insulin receptor (IR) autophosphorylation. A PC-1 variant (K121Q, with lysine 121 replaced by glutamine) is also associated with whole-body insulin resistance when not overexpressed. To better understand the effects of the Q allele on IR function and downstream signaling, we transfected cultured cells with cDNAs for either the Q or the K alleles. In human MCF-7 cells, the Q allele was severalfold more effective (P < 0.05-0.01) than the K allele in reducing insulin stimulation of IR autophosphorylation, insulin receptor substrate-1 phosphorylation, phosphatidylinositol 3-kinase activity, glycogen synthesis, and cell proliferation. Similar data on IR autophosphorylation inhibition were also obtained in mouse R-/hIR and human HEK 293 cell lines. In transfected MCF-7 cells, 125I-labeled insulin binding and IR content were unchanged, and PC-1 overexpression did not influence IGF-1 stimulation of IGF-1 receptor autophosphorylation. Both the Q and K alleles directly interacted with the IR, as documented by coimmunoprecipitation assays. This interaction was greater for the Q allele than for the K allele (P < 0.01), suggesting that direct PC-1-IR interactions are important for the PC-1 inhibitory effect on insulin signaling. In conclusion, the Q allele has stronger inhibitory activity on IR function and insulin action than the more common K allele, and this is likely a consequence of the intrinsic characteristics of the molecule, which more strongly interacts with the IR.

Alleles↗

A cluster of three single nucleotide polymorphisms in the 3'-untranslated region of human glycoprotein PC-1 gene stabilizes PC-1 mRNA and is associated with increased PC-1 protein content and insulin resistance-related abnormalities.

Glycoprotein PC-1 inhibits insulin signaling and, when overexpressed, plays a role in human insulin resistance. Mechanisms of PC-1 overexpression are unknown. We have identified a haplotype in the 3'-untranslated region of the PC-1 gene that may modulate PC-1 expression and confer an increased risk for insulin resistance. Individuals from Sicily, Italy, carrying the "P" haplotype (i.e., a cluster of three single nucleotide polymorphisms: G2897A, G2906C, and C2948T) were at higher risk (P < 0.01) for insulin resistance and had higher (P < 0.05) levels of plasma glucose and insulin during an oral glucose tolerance test and higher levels of cholesterol, HDL cholesterol, and systolic blood pressure. They also had higher (P < 0.05-0.01) PC-1 protein content in both skeletal muscle and cultured skin fibroblasts. In CHO cells transfected with either P or wild-type cDNA, specific PC-1 mRNA half-life was increased for those transfected with P (t/2 = 3.73 +/- 1.0 vs. 1.57 +/- 0.2 h; P < 0.01). In a population of different ethnicity (Gargano, East Coast Italy), patients with type 2 diabetes (the most likely clinical outcome of insulin resistance) had a higher P haplotype frequency than healthy control subjects (7.8 vs. 1.5%, P < 0.01), thus replicating the association between the P allele and the insulin resistance-related abnormalities observed among Sicilians. In conclusion, we have identified a possible molecular mechanism for PC-1 overexpression that confers an increased risk for insulin resistance-related abnormalities.

3' Untranslated Regions↗

Confocal multilaser focusing and single-laser characterization of ultraviolet excitable stains of cellular preparations.

BACKGROUND: The aims of this study were (1) to realign cellular preparations when spots and structures are excited by different lasers of a confocal laser scanning microscope (multilaser studies); (2) to avoid the use of realigment methods by selecting fluorochromes that can be excited by only one laser (single-laser experiments). METHODS: In multilaser studies, we used propidium iodide fluorescent beads, as well as tetramethyl rhodamine isothiocyanate (TRITC), fluorescein isothiocyanate (FITC), and 4'-6 diamidino-2-phenylindole (DAPI)-stained human cancer lines. They were excited using HeNe, argon, and ultraviolet (UV) argon laser lines of a confocal laser scanning microscope. Single-laser experiments using UV excitation only were performed using europium as a model for magnetic resonance paramagnetic contrast agents. Nuclei of human cancer lines and tissue were counterstained by DAPI and cytoplasms were labeled with ELF-97 substrates. Factor analysis of medical images (FAMIS) and correlation methods were used to realign shifted images, focus images, and characterize each fluorochrome when necessary. RESULTS: In multilaser studies, superimposition of factor images corrected Z shifts and correlation methods provided X, Y correction values. In single-laser experiments, each fluorochrome was clearly distinguished in the group of fluorochromes. Estimated images in both studies showed colocalizations of structures. CONCLUSIONS: It is possible to characterize differences in the focus and alignment of fluorescent probes and to correct them. It is also possible to study colocalization of UV excitable fluorochromes (DAPI, ELF-97, europium) in cellular and tissular preparations via multilaser or single-laser experiments.

Europium↗

Factor analysis of confocal image sequences of human papillomavirus DNA revealed with fast red in cervical tissue sections stained with TOTO-iodide.

OBJECTIVE: To visualize and localize specific DNA sequences by fluorescence in situ hybridization, confocal laser scanning microscopy (CLSM) and factor analysis of biomedical image sequences (FAMIS). STUDY DESIGN: Human papillomavirus (HPV) DNA was identified in cervical tissue sections with biotinylated DNA probes recognizing the whole genome of HPV DNA types 18 and 16, and DNA-DNA hybrids were revealed by streptavidin-alkaline phosphatase and Fast Red (FR). Cell nuclei were counterstained with TOTO-iodide. Image sequences were obtained using successive dynamic or spectral sequences of images on different optical slices from CLSM. The location of fluorescent signals inside tissue preparations was determined by FAMIS and/or selection of filters at emission. Image sequences were summarized into a reduced number of images, called "factor images," and curves, called "factors." Factors estimate spectral patterns and depth emission profiles. Factor images correspond to spatial distributions of the different factors. RESULTS: We distinguished between FR and nucleus staining in HPV DNA hybridization signals by taking into account differences in their spectral patterns and improved visualization by taking into account differences in their focus (depth emission profiles). CONCLUSION: FAMIS, together with CLSM, made possible the detection and characterization of HPV DNA sequences in cells of cervical tissue sections.

Azo Compounds↗

Relative impact of scatter, collimator response, attenuation, and finite spatial resolution corrections in cardiac SPECT.

UNLABELLED: We determined the relative effect of corrections for scatter, depth-dependent collimator response, attenuation, and finite spatial resolution on various image characteristics in cardiac SPECT. METHODS: Monte Carlo simulations and real acquisition of a 99mTc cardiac phantom were performed under comparable conditions. Simulated and acquired data were reconstructed using several correction schemes that combined different methods for scatter correction (3 methods), depth-dependent collimator response correction (frequency-distance principle), attenuation correction (nonuniform Chang correction or within an iterative reconstruction algorithm), and finite spatial resolution correction (use of recovery coefficients). Five criteia were considered to assess the effect of the processing schemes: bull's-eye map (BEM) uniformity, contrast between the left ventricle (LV) wall and the LV cavity, spatial resolution, signal-to-noise ratio (SNR), and percent errors with respect to the known LV wall and liver activities. RESULTS: Similar results were obtained for the simulated and acquired data. Scatter correction significantly improved contrast and absolute quantitation but did not have noticeable effects on BEM uniformity or on spatial resolution and reduced the SNR. Correction for the depth-dependent collimator response improved spatial resolution from 13.3 to 9.5 mm in the LV region, improved absolute quantitation and contrast, but reduced the SNR. Correcting for attenuation was essential for restoring BEM uniformity (78% and 89% without and with attenuation correction, respectively [ideal value being 100%]) and accurate absolute activity quantitation (errors in estimated LV wall and liver activity decreased from 90% without attenuation correction to approximately20% with attenuation correction only). Although accurate absolute activity quantitation was achieved in the liver using scatter and attenuation corrections only, correction for finite spatial resolution was needed to estimate LV wall activity within 10%. CONCLUSION: The respective effects of corrections for scatter, depth-dependent collimator response, attenuation, and finite spatial resolution on different image features in cardiac SPECT were quantified for a specific acquisition configuration. These results give indications regarding the improvements to be expected when using a specific processing scheme involving some or all corrections.

Heart↗

5-Lipoxygenase upregulation by dexamethasone in human mast cells.

In spite of intensive research, our understanding of the regulation of expression of 5-LO (the key enzyme in the leukotriene metabolism) remains fragmentary. We investigated the effects of dexamethasone on the expression of this gene in a binary model consisting of two clones of the human mast cell line HMC-1, one with a 5-LO-negative and the other with a 5-LO-positive phenotype, respectively. When dexamethasone was included in the culture medium at a physiologically relevant concentration, biosynthesis of 5-LO derivatives increased considerably not only in the 5-LO-negative HMC-1 cells (approx 10-fold) but also in the 5-LO-positive cells, characterized by an already substantial enzyme activity. Consistently, Northern blot analysis revealed that a dramatic increase in the abundance of 5-LO mRNA occurred when the cells were exposed to dexamethasone. Likewise, a significant increase in the immunoreactive 5-LO protein was detected by Western blotting. In contrast, dexamethasone seemed to have no effect on the expression of two other genes of pivotal importance in leukotriene biosynthesis, viz. FLAP and LTC(4) synthase. We conclude that in human mast cells glucocorticoids effectively and selectively upregulate the expression of 5-LO.

5-Lipoxygenase-Activating Proteins↗

Respective roles of scatter, attenuation, depth-dependent collimator response and finite spatial resolution in cardiac single-photon emission tomography quantitation: a Monte Carlo study.

The purpose of this study was to investigate the relative influence of scatter, attenuation, depth-dependent collimator response and finite spatial resolution upon the image characteristics in cardiac single-photon emission tomography (SPET). An acquisition of an anthropomorphic cardiac phantom was performed together with corresponding SPET Monte Carlo simulations. The cardiac phantom and the Monte Carlo simulations were designed so that the effect of scatter, attenuation, depth-dependent collimator response and finite spatial resolution could be studied individually and in combination. The impact of each physical effect and of combinations of effects was studied in terms of absolute and relative quantitative accuracy, spatial resolution and signal-to-noise ratio (SNR) in the resulting images. No corrections for these effects were assessed. Results obtained from Monte Carlo simulations and real acquisitions were in excellent agreement. Attenuation introduced about 90% activity underestimation in a 10-mm-thick left ventricle wall while finite spatial resolution alone introduced about 30% activity underestimation. Scatter had a negligible impact on quantitative accuracy in the recontructed slices when attenuation was present. Neither bull's eye map homogeneity nor contrast between a hot and a cold region were affected by depth-dependent collimator response or finite spatial resolution. Bull's eye map homogeneity was severely affected by attenuation but not by scatter. Attenuation and scatter reduced contrast by about 20% each. Both attenuation and scatter increased the full-width at half-maximum (FWHM) characterizing the spatial resolution of the imaging system by approximately 1 mm each but the main effect responsible for the observed 11-mm FWHM spatial resolution was the depth-dependent collimator response. SNR was reduced by a factor of approximately 2.5 because of attenuation, while scattered counts increased SNR by approximately 10%. In conclusion, the quantification of the relative influence of the different physical effects showed that attenuation is definitely the major phenomenon affecting cardiac SPET imaging accuracy, but that finite spatial resolution, scatter and depth-dependent collimator response also contribute significantly to the errors in absolute and relative quantitation and to the poor spatial resolution.

Computer Simulation↗

Four-dimensional factor analysis of confocal image sequences (4D-FAMIS) to detect and characterize low copy numbers of human papillomavirus DNA by FISH in HeLa and SiHa cells.

Visualization and localization of specific DNA sequences were performed by fluorescence in situ hybridization, confocal laser scanning microscopy (CLSM), and four-dimensional factor analysis of biomedical image sequences (4D-FAMIS). HeLa and SiHa cells containing, respectively 20-50 and 1-2 copies per cell of human papillomavirus (HPV) DNA type 18 and 16 integrated in cellular DNA were used as models. HPV-DNA was identified using DNA probes containing the whole genome of HPV-DNA type 18 or 16, and DNA-DNA hybrids were revealed by alkaline phosphatase and Fast Red. Cell nuclei were counterstained with thiazole orange (TO) or TOTO-iodide. 4D image sequences were obtained using successive dynamic or spectral sequences of images on different optical sections from CLSM. The location of fluorescent signals within the preparations was determined by FAMIS. This original method summarizes image sequences into a reduced number of images called factor images, and curves called factors. Factors estimate different individual physical behaviours in the sequence such as extinction velocity, spectral patterns and depth emission profiles. Factor images correspond to spatial distributions of the different factors. We distinguished between Fast Red and nucleus stainings in HPV-DNA hybridization signals by taking into account differences in their extinction velocities (fluorescence decay rate) or spectral patterns, and in their focus (depth emission profiles). In HeLa cells, factor images showed that Fast-Red-stained targets could be distinguished from nucleus stainings, and were located on different focal planes of the nuclei. In SiHa cells, 4D-FAMIS determined as few as 1-2 copies per cell of HPV-DNA type 16 located in continuous focal planes. Therefore, 4D-FAMIS, together with CLSM, made the detection and characterization of low copy numbers of genes in whole cells possible.

Cell Nucleus↗

A spline-regularized minimal residual algorithm for iterative attenuation correction in SPECT.

In SPECT, regularization is necessary to avoid divergence of the iterative algorithms used for non uniform attenuation compensation. In this paper, we propose a spline-based regularization method for the minimal residual algorithm. First, the acquisition noise is filtered using a statistical model involving spline smoothing so that the filtered projections belong to a Sobolev space with specific continuity and derivability properties. Then, during the iterative reconstruction procedure, the continuity of the inverse Radon transform between Sobolev spaces is used to design a spline-regularized filtered backprojection method, by which the known regularity properties of the projections determine those of the corresponding reconstructed slices. This ensures that the activity distributions estimated at each iteration present regularity properties, which avoids computational noise amplification, thus stabilizing the iterative process. Analytical and Monte Carlo simulations are used to show that the proposed spline-regularized minimal residual algorithm converges to a satisfactory stable solution in terms of restored activity and homogeneity, using at most 25 iterations, whereas the non regularized version of the algorithm diverges. Choosing the number of iterations is therefore no longer a critical issue for this reconstruction procedure.

Algorithms↗