Simulation of charge transport in pixelated CdTe.

The Voxel Imaging PET (VIP) Pathfinder project intends to show the advantages of using pixelated semiconductor technology for nuclear medicine applications to achieve an improved image reconstruction without efficiency loss. It proposes designs for Positron Emission Tomography (PET), Positron Emission Mammography (PEM) and Compton gamma camera detectors with a large number of signal channels (of the order of 106). The design is based on the use of a pixelated CdTe Schottky detector to have optimal energy and spatial resolution. An individual read-out channel is dedicated for each detector voxel of size 1 × 1 × 2 mm3 using an application-specific integrated circuit (ASIC) which the VIP project has designed, developed and is currently evaluating experimentally. The behaviour of the signal charge carriers in CdTe should be well understood because it has an impact on the performance of the readout channels. For this purpose the Finite Element Method (FEM) Multiphysics COMSOL software package has been used to simulate the behaviour of signal charge carriers in CdTe and extract values for the expected charge sharing depending on the impact point and bias voltage. The results on charge sharing obtained with COMSOL are combined with GAMOS, a Geant based particle tracking Monte Carlo software package, to get a full evaluation of the amount of charge sharing in pixelated CdTe for different gamma impact points.

Evaluation of Origin Ensemble algorithm for image reconstruction for pixelated solid-state detectors with large number of channels.

The Voxel Imaging PET (VIP) Pathfinder project intends to show the advantages of using pixelated solid-state technology for nuclear medicine applications. It proposes designs for Positron Emission Tomography (PET), Positron Emission Mammography (PEM) and Compton gamma camera detectors with a large number of signal channels (of the order of 106). For PET scanners, conventional algorithms like Filtered Back-Projection (FBP) and Ordered Subset Expectation Maximization (OSEM) are straightforward to use and give good results. However, FBP presents difficulties for detectors with limited angular coverage like PEM and Compton gamma cameras, whereas OSEM has an impractically large time and memory consumption for a Compton gamma camera with a large number of channels. In this article, the Origin Ensemble (OE) algorithm is evaluated as an alternative algorithm for image reconstruction. Monte Carlo simulations of the PET design are used to compare the performance of OE, FBP and OSEM in terms of the bias, variance and average mean squared error (MSE) image quality metrics. For the PEM and Compton camera designs, results obtained with OE are presented.

Energy and coincidence time resolution measurements of CdTe detectors for PET.

We report on the characterization of 2 mm thick CdTe diode detector with Schottky contacts to be employed in a novel conceptual design of PET scanner. Results at -8°C with an applied bias voltage of -1000 V/mm show a 1.2% FWHM energy resolution at 511 keV. Coincidence time resolution has been measured by triggering on the preamplifier output signal to improve the timing resolution of the detector. Results at the same bias and temperature conditions show a FWHM of 6 ns with a minimum acceptance energy of 500 keV. These results show that pixelated CdTe Schottky diode is an excellent candidate for the development of next generation nuclear medical imaging devices such as PET, Compton gamma cameras, and especially PET-MRI hybrid systems when used in a magnetic field immune configuration.

Pixelated CdTe detectors to overcome intrinsic limitations of crystal based positron emission mammographs.

A positron emission mammograph (PEM) is an organ dedicated positron emission tomography (PET) scanner for breast cancer detection. State-of-the-art PEMs employing scintillating crystals as detection medium can provide metabolic images of the breast with significantly higher sensitivity and specificity with respect to standard whole body PET scanners. Over the past few years, crystal PEMs have dramatically increased their importance in the diagnosis and treatment of early stage breast cancer. Nevertheless, designs based on scintillators are characterized by an intrinsic deficiency of the depth of interaction (DOI) information from relatively thick crystals constraining the size of the smallest detectable tumor. This work shows how to overcome such intrinsic limitation by substituting scintillating crystals with pixelated CdTe detectors. The proposed novel design is developed within the Voxel Imaging PET (VIP) Pathfinder project and evaluated via Monte Carlo simulation. The volumetric spatial resolution of the VIP-PEM is expected to be up to 6 times better than standard commercial devices with a point spread function of 1 mm full width at half maximum (FWHM) in all directions. Pixelated CdTe detectors can also provide an energy resolution as low as 1.5% FWHM at 511 keV for a virtually pure signal with negligible contribution from scattered events.

Collagenous colitis and collagenous gastritis in a 9 year old girl: a case report and review of the literature.

Collagenous gastritis is a rare disease in the general population and collagenous colitis has seldom been reported in children. We report a girl with both diseases and review the literature on this association afetr a systematic search of Pubmed, Medline and Embase databases.. The girl, diagnosed of collagenous colitis at the age of 2 years, started with abdominal pain and anaemia at the age of 9 years and was diagnosed of collagenous gastritis in the gastric biopsies. After review of the literature, we found 66 reported cases (33 children, 33 adults, 68% females), 56 patients with collagenous gastritis and 16 children with collagenous colitis. Both disorders coexisted in 20 patients. The main presenting symptoms are abdominal pain and anaemia in patients with collagenous gastritis and diarrhoea and weight loss in patients with both disorders. Hypoalbuminemia was found in 9 patients with both diseases and protein losing enteropathy was demonstrated in 3 cases. Deposits of collagen in the duodenum were observed in 13 of 19 patients with both diseases. Seventeen of 66 patients had associated autoimmune disorders, particularly in patients with both diseases (35%). These conditions have a chronic course but gastric or colonic malignancies have not been communicated to date. In conclusion, collagenous gastritis and collagenous colitis mainly affects women and can occur at any age. Their association is exceptional. These disorders, although rare, should be considered in patients with anaemia and epigastric pain, watery diarrhoea or protein losing enteropathy.

Allergy assessment in children with eosinophilic esophagitis.

BACKGROUND: Eosinophilic esophagitis (EoE) is of growing interest for pediatricians and allergists. There is no general agreement about diagnostic and clinical management procedures. The objective of this prospective, observational study was to evaluate the efficacy of a protocol for the etiologic diagnosis and accurate treatment of EoE in the pediatric population. PATIENTS AND METHODS: Starting in 2001, patients aged 0 to 14 years with a diagnosis of EoE were consecutively included in a protocol which included an allergy study. Depending on the results, an avoidance or elemental diet was established. Topical corticosteroids were prescribed to patients who rejected the diet. Clinical, endoscopic, and histological evaluation was performed to assess response. In the case of disease remission, challenge tests were performed to identify the offending food. RESULTS: Seventeen patients were included. Most of them were male (14/17) and a high percentage (88%) had a history of allergy as well as a history of atopy in parents. Fifteen patients were sensitized to 1 or more foods. With this protocol and the subsequent treatment, 9 out of 17 patients were cured (1 out of 4 with swallowed corticosteroids, 3 out of 3 with an elemental diet, and 5 out of 12 with an avoidance diet). The offending food was identified in 8117 patients. Milk and eggs were the most common foods implicated. CONCLUSIONS: The allergy study was a useful diagnostic tool but it was not sufficient to identify the offending food.An elemental diet should be attempted before food is excluded as the cause of the disease.

Síndrome de Rasmussen: una enfermedad autoinmune / Rasmussen's syndrome, an autoimmune disease

La enfermedad de Rasmussen es un trastorno cerebral inflamatorio, crónico y progresivo que se manifiesta con crisis focales motoras neocorticales resistentes al tratamiento y que culmina en un deterioro grave con hemiparesia, retraso cognitivo y afasia. Dentro de la fisiopatología de esta enfermedad se han involucrado infecciones virales, así como la existencia de anticuerpos contra el receptor GluR3 cerebral y se ha barajado la posible mediación celular T en el proceso inflamatorio cerebral. El tratamiento clásico consistía en hemisferectomías de distinta magnitud según la afectación cerebral existente. Muy recientemente se está empezando a estudiar la asociación de trastornos epilépticos resistentes al tratamiento con la implicación de fenómenos autoinmunes debido a la existencia de anticuerpos antidescarboxilasa del ácido glutámico (anti-GAD). El descubrimiento de esta asociación permitió un nuevo enfoque y se empezaron a ensayar tratamientos alternativos con inmunosupresores, inmunoglobulinas, corticoides, plasmaféresis, solos o en combinación, con éxito variable. Se describe el caso de un niño diagnosticado de enfermedad de Rasmussen en fase precoz en el que resultaron positivos los anticuerpos anti-GAD. Recibió tratamiento con inmunoglobulinas y corticoides, con lo cual desaparecieron los síntomas y se negativizaron los anticuerpos. (AU)

[Rasmussen's syndrome, an autoimmune disease]. / Síndrome de Rasmussen: una enfermedad autoinmune.

Rasmussen's disease is an inflammatory, chronic and progressive brain disorder that usually presents with neocortical focal seizures resistant to conventional treatment and culminates in severe deterioration with hemiparesis, cognitive decline and aphasia. Viral infections and antibodies to the GluR3 receptor have been implicated in the physiopathology of this illness and T-cell mediation may play a role in the cerebral inflammatory process. Classical treatment consists of hemispherectomy of various magnitudes depending on cerebral involvement. The association between therapy-resistant epilepsy and autoimmune phenomena due to antibodies against glutamic acid decarboxylase (anti-GAD) have very recently begun to be studied. The discovery of this association led to a new focus and alternative therapies with immunosuppressors, immunoglobulins, steroids and plasmapheresis, alone or in combination, have begun to be tested with variable success. We describe a boy who was diagnosed in the early stages of Rasmussen's syndrome. He tested positive for anti-GAD antibodies and received treatment with immunoglobulins and steroids. After treatment the boy tested negative for anti-GAD antibodies and he remains asymptomatic after ten months.

Linfocitos intraepiteliales en la enfermedad celíaca / Intraepithelial lymphocytes in celiac disease

La enfermedad celíaca es una intolerancia permanente a los componentes del gluten que cursa con una alteración de la mucosa del intestino delgado generalmente reversible al excluir el gluten de la dieta. La patogenia del proceso es inmunitaria y se sabe que, además de un estrechísimo ligamiento con ciertos alelos HLA, en esta enfermedad existen alteraciones constantes en los linfocitos intraepiteliales (i-LIE). El desarrollo de una técnica para su determinación por citometría de flujo (CMF) nos ha permitido profundizar en el conocimiento de estas alteraciones y utilizar su determinación en el diagnóstico clínico. Nuestra experiencia demuestra que esta prueba presenta una excelente sensibilidad y especificidad en el diagnóstico de la enfermedad celíaca y que su utilidad es especialmente relevante en las presentaciones atípicas de la enfermedad. En este trabajo se resumen los resultados obtenidos y se discuten algunas de las hipótesis que se han vertido acerca de la posible participación de los LIE en la patogenia de la enfermedad (AU)

[Intraepithelial lymphocytes in celiac disease]. / Linfocitos intraepiteliales en la enfermedad celíaca.

Coeliac disease (CD) is a permanent intolerance to gluten that provokes alterations in the mucosa of the small intestine. The disease can usually be controlled by excluding gluten from the diet. CD is immunologically-mediated, with a strong linkage to certain HLA alleles and a permanently altered intraepithelial lymphocytes (IEL) pattern. The development of a flow cytometric technique for the evaluation of IEL subsets has increased our understanding of these alterations and has prepared the ground for its clinical application. Our experience shows that this procedure has excellent sensitivity and specificity in the diagnosis of CD and that it is particularly useful in the evaluation of atypical presentations of the disease. The present article reviews our experience in the diagnosis of CD and discusses some of the hypotheses that have been put forward on the possible role of IEL in its pathogenesis.