Tomografía por emisión de positrones en el cáncer de mama

PET18FDG is an imaging diagnostic technique that shows changes in glycolitic metabolism that appear at a very early phases in the tumoral process. The main limitation of PET in breast cancer is the detection of small tumor lesions and axillary micrometastases. However it offers important information in the staging of high risk patients, in clinical relapse or in therapeutic evaluation. The new PET-CT devices offer advantages over conventional techniques. It provides a greater precision in the localization of tumoral foci. In spite of current difficulties for clinical applications, fluoro-estradiol (18F-ES) offers the possibilty of studying the presence of estrogenic receptors both in the primary and in the metastases. It may prove to be a useful tool to obtain information about therapeutic management and prognosis of breast cancer

Evaluation of spacial resolution of a PET scanner through the simulation and experimental measurement of the Recovery coefficient

Purpose: In order to measure spatial resolution of a PET tomograph in clinical conditions, this study describes and validates a method based on the recovery coefficient, a factor required to compensate underestimation in measured radioactivity concentration for small structures. Methods: In a PET image, the recovery factors of radioactive spheres were measured and their comparison with simulated recovery coefficients yielded the tomographic spatial resolution. Following this methodology, resolution was determined in different surrounding media and several conditions for reconstruction, including clinical conditions for brain PET studies. All spatial resolution values were compared with those obtained using classical methods with point and line sources. Results: In each considered condition, spatial resolution of the PET image estimated using the recovery coefficient showed good agreement with classical methods measurements, validating the procedure. Conclusion: Measurement of the recovery coefficient provides an assessment of tomographic spatial resolution, particularly in clinical studies conditions

Development and clinical evaluation of a simple optical method to detect and measure patient external motion

A simple and independent system to detect and measure the position of a number of points in space was devised and implemented. Its application aimed to detect patient motion during radiotherapy treatments, alert of out-of-tolerances motion, and record the trajectories for subsequent studies. The system obtains the 3D position of points in space, through its projections in 2D images recorded by two cameras. It tracks black dots on a white sticker placed on the surface of the moving object. The system was tested with linear displacements of a phantom, circular trajectories of a rotating disk, oscillations of an in-house phantom, and oscillations of a 4D phantom. It was also used to track 461 trajectories of points on the surface of patients during their radiotherapy treatments. Trajectories of several points were reproduced with accuracy better than 0.3 mm in the three spatial directions. The system was able to follow periodic motion with amplitudes lower than 0.5 mm, to follow trajectories of rotating points at speeds up to 11.5 cm/s, and to track accurately the motion of a respiratory phantom. The technique has been used to track the motion of patients during radiotherapy and to analyze that motion. The method is flexible. Its installation and calibration are simple and quick. It is easy to use and can be implemented at a very affordable price. Data collection does not involve any discomfort to the patient and does not delay the treatment, so the system can be used routinely in all treatments. It has an accuracy similar to that of other, more sophisticated, commercially available systems. It is suitable to implement a gating system or any other application requiring motion detection, such as 4D CT, MRI or PET

Monoaminergic PET imaging and histopathological correlation in unilateral and bilateral 6-hydroxydopamine lesioned rat models of Parkinson's disease: a longitudinal in-vivo study

Carbon-11 labeled dihydrotetrabenazine (11C-DTBZ) binds to the vesicular monoamine transporter 2 and has been used to assess nigro-striatal integrity in animal models and patients with Parkinson's disease. Here, we applied 11C-DTBZ positron emission tomography (PET) to obtain longitudinally in-vivo assessment of striatal dopaminergic loss in the classic unilateral and in a novel bilateral 6-hydroxydopamine (6-OHDA) lesion rat model. Forty-four Sprague–Dawley rats were divided into 3 sub-groups: 1. 6-OHDA-induced unilateral lesion in the medial forebrain bundle, 2. bilateral lesion by injection of 6-OHDA in the third ventricle, and 3. vehicle injection in either site. 11C-DTBZ PET studies were investigated in the same animals successively at baseline, 1, 3 and 6 weeks after lesion using an anatomically standardized volumes-of-interest approach. Additionally, 12 rats had PET and Magnetic Resonance Imaging to construct a new 11C-DTBZ PET template. Behavior was characterized by rotational, catalepsy and limb-use asymmetry tests and dopaminergic striatal denervation was validated post-mortem by immunostaining of the dopamine transporter (DAT). 11C-DTBZ PET showed a significant decrease of striatal binding (SB) values one week after the unilateral lesion. At this point, there was a 60% reduction in SB in the affected hemisphere compared with baseline values in 6-OHDA unilaterally lesioned animals. A 46% symmetric reduction over baseline SB values was found in bilaterally lesioned rats at the first week after lesion. SB values remained constant in unilaterally lesioned rats whereas animals with bilateral lesions showed a modest (22%) increase in binding values at the 3rd and 6th weeks post-lesion. The degree of striatal dopaminergic denervation was corroborated histologically by DAT immunostaining. Statistical analysis revealed a high correlation between 11C-DTBZ PET SB and striatal DAT immunostaining values (r = 0.95, p < 0.001). The data presented here indicate that 11C-DTBZ PET may be used to ascertain changes occurring in-vivo throughout the evolution of nigro-striatal dopaminergic neurodegeneration, mainly in the unilateral 6-OHDA lesion rat

New MRI, 18F-DOPA and 11C-(+)-alpha-dihydrotetrabenazine templates for Macaca fascicularis neuroimaging: advantages to improve PET quantification

Normalization of neuroimaging studies to a stereotaxic space allows the utilization of standard volumes of interest (VOIs) and voxel-based analysis (SPM). Such spatial normalization of PET and MRI studies requires a high quality template image. The aim of this study was to create new MRI and PET templates of 18F-DOPA and 11C-(+)-α-dihydrotetrabenazine (11C-DTBZ) of the Macaca fascicularis brain, an important animal model of Parkinson's disease. MRI template was constructed as a smoothed average of the scans of 15 healthy animals, previously transformed into the space of one representative MRI. In order to create the PET templates, 18F-DOPA and 11C-DTBZ PET of the same subjects were acquired in a dedicated small animal PET scanner and transformed to the created MRI template space. To validate these templates for PET quantification, parametric values obtained with a standard VOI-map applied after spatial normalization to each template were statistically compared to results computed using individual VOIs drawn for each animal. The high correlation between both procedures validated the utilization of all the templates, improving the reproducibility of PET analysis. To prove the utility of the templates for voxel-based quantification, dopamine striatal depletion in a representative monkey treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was assessed by SPM analysis of 11C-DTBZ PET. A symmetric reduction in striatal 11C-DTBZ uptake was detected in accordance with the induced lesion. In conclusion, templates of M. fascicularis brain have been constructed and validated for reproducible and automated PET quantification. All templates are electronically available via the internet

Statistical parametric maps of (18)F-FDG PET and 3-D autoradiography in the rat brain: a cross-validation study

PURPOSE: Although specific positron emission tomography (PET) scanners have been developed for small animals, spatial resolution remains one of the most critical technical limitations, particularly in the evaluation of the rodent brain. The purpose of the present study was to examine the reliability of voxel-based statistical analysis (Statistical Parametric Mapping, SPM) applied to (18)F-fluorodeoxyglucose (FDG) PET images of the rat brain, acquired on a small animal PET not specifically designed for rodents. The gold standard for the validation of the PET results was the autoradiography of the same animals acquired under the same physiological conditions, reconstructed as a 3-D volume and analysed using SPM. METHODS: Eleven rats were studied under two different conditions: conscious or under inhalatory anaesthesia during (18)F-FDG uptake. All animals were studied in vivo under both conditions in a dedicated small animal Philips MOSAIC PET scanner and magnetic resonance images were obtained for subsequent spatial processing. Then, rats were randomly assigned to a conscious or anaesthetized group for postmortem autoradiography, and slices from each animal were aligned and stacked to create a 3-D autoradiographic volume. Finally, differences in (18)F-FDG uptake between conscious and anaesthetized states were assessed from PET and autoradiography data by SPM analysis and results were compared. RESULTS: SPM results of PET and 3-D autoradiography are in good agreement and led to the detection of consistent cortical differences between the conscious and anaesthetized groups, particularly in the bilateral somatosensory cortices. However, SPM analysis of 3-D autoradiography also highlighted differences in the thalamus that were not detected with PET. CONCLUSION: This study demonstrates that any difference detected with SPM analysis of MOSAIC PET images of rat brain is detected also by the gold standard autoradiographic technique, confirming that this methodology provides reliable results, although partial volume effects might make it difficult to detect slight differences in small regions

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Optimización de la dosimetría en la planificación de los tratamientos de radioembolización hepática con microesferas de 90Y

La radioembolización (RE) consiste en la administración por vía intraarterial hepática de microesferas marcadas con un isótopo radiactivo que emita radiación de corto alcance, que permita impartir dosis absorbidas elevadas en el tejido tumoral y limitar la dosis absorbida en el tejido sano. Su eficacia se basa en la vascularización característica del hígado y de los tumores hepáticos. El tejido hepático sano recibe su flujo sanguíneo a través de la vena porta, mientras que los tumores hepáticos se irrigan principalmente por la arteria hepática. El pequeño tamaño de las microesferas permite que lleguen hasta el tumor a través de la vasculatura hepática, quedando permanentemente implantadas dentro del sistema vascular tumoral e impidiendo su paso a la circulación venosa. La planificación de los tratamientos de RE, a partir de la imagen 99mTc-MAA SPECT-CT, es la única herramienta disponible que permite realizar una evaluación dosimétrica personalizada previa a la administración del tratamiento. El cálculo preciso de las dosis absorbidas favorece la optimización tanto de la selección de pacientes candidatos a RE como del proceso de planificación para maximizar su eficacia terapéutica y minimizar la toxicidad en tejido sano. Por tanto, una metodología dosimétrica optimizada y reproducible es no sólo importante, sino esencial. En la actualidad, prácticamente ninguno de los procesos que se engloban dentro de un procedimiento dosimétrico está completamente estandarizado. En este contexto, surge un gran interés en abordar la comparación de diferentes técnicas en una única serie de pacientes, que facilite la estandarización del uso de las mismas. El objetivo de este estudio de investigación es optimizar y estandarizar el procedimiento dosimétrico en la planificación de los tratamientos de RE hepática con 90Y-microesferas, cuantificando la repercusión de cada variante metodológica en la dosis absorbida ycaracterizando su impacto clínico. Se consideraron cuatro modelos dosimétricos diferentes, dos métodos multicompartimentales, el método de partición y el modelo de partición multitumor planteado como novedad en este trabajo, y dos métodos de dosimetría a nivel de vóxel. Se compararon las dosis absorbidas, tanto en el tejido sano como en el tejido tumoral, resultantes de aplicar estos modelos dosimétricos sobre las imágenes pre-tratamiento. Del análisis de los resultados obtenidos, se desprende que llevar a cabo una segmentación completa de los compartimentos, a partir de los contornos del hígado, el volumen diana y cada una de las lesiones individuales que constituyen el conglomerado tumoral, contribuye a que los cálculos dosimétricos sean más precisos, lo que permite optimizar la selección de pacientes candidatos a RE y aporta información importante para decidir el mejor esquema terapéutico para el paciente. Además, las metodologías empleadas para determinar parámetros como el índice TN y el factor de calibración han demostrado tener un impacto importante en el cálculo de las dosis absorbidas resultantes. Así, el procedimiento empleado tiene un papel fundamental en la dosimetría de los tratamientos de RE, y es esencial establecer una única metodología para su cálculo. El nuevo modelo de partición multi-tumor es una herramienta fácil de implementar y podría ser de gran utilidad en aquellos centros en los que no es posible implementar métodos de dosimetría a nivel de vóxel, ya que aporta una mayor precisión que el modelo de partición estándar en el cálculo de la dosis absorbida en el tejido tumoral. Como resultado final de este trabajo se diseñó un algoritmo de recomendaciones, cuyo principal objetivo es contribuir a la estandarización de los métodos empleados en la dosimetría pre-tratamiento. Así, en función de las herramientas disponibles y de los datos recogidos de cada paciente, cada centro puede elegir la forma de proceder más adecuada para el cálculo de las dosis absorbidas

Optimización de la dosimetría en la planificación de los tratamientos de radioembolización hepática con microesferas de 90Y

La radioembolización (RE) consiste en la administración por vía intraarterial hepática de microesferas marcadas con un isótopo radiactivo que emita radiación de corto alcance, que permita impartir dosis absorbidas elevadas en el tejido tumoral y limitar la dosis absorbida en el tejido sano. Su eficacia se basa en la vascularización característica del hígado y de los tumores hepáticos. El tejido hepático sano recibe su flujo sanguíneo a través de la vena porta, mientras que los tumores hepáticos se irrigan principalmente por la arteria hepática. El pequeño tamaño de las microesferas permite que lleguen hasta el tumor a través de la vasculatura hepática, quedando permanentemente implantadas dentro del sistema vascular tumoral e impidiendo su paso a la circulación venosa. La planificación de los tratamientos de RE, a partir de la imagen 99mTc-MAA SPECT-CT, es la única herramienta disponible que permite realizar una evaluación dosimétrica personalizada previa a la administración del tratamiento. El cálculo preciso de las dosis absorbidas favorece la optimización tanto de la selección de pacientes candidatos a RE como del proceso de planificación para maximizar su eficacia terapéutica y minimizar la toxicidad en tejido sano. Por tanto, una metodología dosimétrica optimizada y reproducible es no sólo importante, sino esencial. En la actualidad, prácticamente ninguno de los procesos que se engloban dentro de un procedimiento dosimétrico está completamente estandarizado. En este contexto, surge un gran interés en abordar la comparación de diferentes técnicas en una única serie de pacientes, que facilite la estandarización del uso de las mismas. El objetivo de este estudio de investigación es optimizar y estandarizar el procedimiento dosimétrico en la planificación de los tratamientos de RE hepática con 90Y-microesferas, cuantificando la repercusión de cada variante metodológica en la dosis absorbida ycaracterizando su impacto clínico. Se consideraron cuatro modelos dosimétricos diferentes, dos métodos multicompartimentales, el método de partición y el modelo de partición multitumor planteado como novedad en este trabajo, y dos métodos de dosimetría a nivel de vóxel. Se compararon las dosis absorbidas, tanto en el tejido sano como en el tejido tumoral, resultantes de aplicar estos modelos dosimétricos sobre las imágenes pre-tratamiento. Del análisis de los resultados obtenidos, se desprende que llevar a cabo una segmentación completa de los compartimentos, a partir de los contornos del hígado, el volumen diana y cada una de las lesiones individuales que constituyen el conglomerado tumoral, contribuye a que los cálculos dosimétricos sean más precisos, lo que permite optimizar la selección de pacientes candidatos a RE y aporta información importante para decidir el mejor esquema terapéutico para el paciente. Además, las metodologías empleadas para determinar parámetros como el índice TN y el factor de calibración han demostrado tener un impacto importante en el cálculo de las dosis absorbidas resultantes. Así, el procedimiento empleado tiene un papel fundamental en la dosimetría de los tratamientos de RE, y es esencial establecer una única metodología para su cálculo. El nuevo modelo de partición multi-tumor es una herramienta fácil de implementar y podría ser de gran utilidad en aquellos centros en los que no es posible implementar métodos de dosimetría a nivel de vóxel, ya que aporta una mayor precisión que el modelo de partición estándar en el cálculo de la dosis absorbida en el tejido tumoral. Como resultado final de este trabajo se diseñó un algoritmo de recomendaciones, cuyo principal objetivo es contribuir a la estandarización de los métodos empleados en la dosimetría pre-tratamiento. Así, en función de las herramientas disponibles y de los datos recogidos de cada paciente, cada centro puede elegir la forma de proceder más adecuada para el cálculo de las dosis absorbidas

Tomografía por emisión de positrones en el cáncer de mama

PET18FDG is an imaging diagnostic technique that shows changes in glycolitic metabolism that appear at a very early phases in the tumoral process. The main limitation of PET in breast cancer is the detection of small tumor lesions and axillary micrometastases. However it offers important information in the staging of high risk patients, in clinical relapse or in therapeutic evaluation. The new PET-CT devices offer advantages over conventional techniques. It provides a greater precision in the localization of tumoral foci. In spite of current difficulties for clinical applications, fluoro-estradiol (18F-ES) offers the possibilty of studying the presence of estrogenic receptors both in the primary and in the metastases. It may prove to be a useful tool to obtain information about therapeutic management and prognosis of breast cancer