PET amiloide en enfermedades neurodegenerativas que cursan con demencia / Amyloid PET in neurodegenerative diseases with dementia

La enfermedad de Alzheimer (EA) es una enfermedad neurodegenerativa que se caracteriza por un deterioro cognitivo progresivo y pérdida de memoria, siendo la causa más común de demencia. Los hallazgos anatomopatológicos de la EA son los depósitos de Aβ amiloide y proteína Tau, que producen disfunción sináptica y muerte neuronal. La PET amiloide es una técnica útil, disponible y no invasiva que nos proporciona información in vivo del depósito amiloide. En las últimas revisiones de los criterios diagnósticos de la EA se definen e incorporan los biomarcadores, que se clasifican en biomarcadores fisiopatológicos o de diagnóstico (aumento de la retención fibrilar amiloide observada por PET o disminución del péptido Aβ1-42 y elevación de las proteínas T-Tau y F-Tau en el LCR) y biomarcadores de neurodegeneración o topográficos (disminución del metabolismo temporoparietal en la PET-FDG y atrofia temporal medial en la RM). Recientemente se han creado unas recomendaciones específicas para la correcta utilización de los biomarcadores, donde se incluye la PET amiloide: deterioro cognitivo persistente/progresivo, deterioro cognitivo atípico, deterioro cognitivo de inicio precoz y diagnóstico diferencial entre EA y otras enfermedades neurodegenerativas que cursan con demencia. Nuevos estudios de investigación y ensayos clínicos están utilizando la PET amiloide en la evaluación y el desarrollo de nuevas terapias para la EA, así como para el estudio de otras enfermedades neurodegenerativas que cursan con demencia. En este trabajo revisamos algunos conceptos generales y profundizamos en el uso de esta nueva técnica y su relación con las enfermedades neurodegenerativas y el resto de las técnicas diagnósticas

Alzheimer's disease (AD) is a neurodegenerative condition characterized by progressive cognitive decline and memory loss, and is the most common form of dementia. Amyloid plaques with neurofibrillary tangles are a neuropathological hallmark of AD that produces synaptic dysfunction and culminates later in neuronal loss. Amyloid PET is a useful, available and non-invasive technique that provides in vivo information about the cortical amyloid burden. In the latest revised criteria for the diagnosis of AD biomarkers were defined and integrated: pathological and diagnostic biomarkers (increased retention on fibrillar amyloid PET or decreased Aβ1-42 and increased T-Tau or P-Tau in CSF) and neurodegeneration or topographical biomarkers (temporoparietal hypometabolism on 18F-FDG PET and temporal atrophy on MRI). Recently specific recommendations have been created as a consensus statement on the appropriate use of the imaging biomarkers, including amyloid PET: early-onset cognitive impairment/dementia, atypical forms of AD, mild cognitive impairment with early age of onset, and to differentiate between AD and other neurodegenerative diseases that occur with dementia. Amyloid PET is also contributing to the development of new therapies for AD, as well as in research studies for the study of other neurodegenerative diseases that occur with dementia where the deposition of Aβ amyloid is involved in its pathogenesis. In this paper, we review some general concepts and study the use of amyloid PET in depth and its relationship with neurodegenerative diseases and other diagnostic techniques

Amyloid PET in neurodegenerative diseases with dementia. / PET amiloide en enfermedades neurodegenerativas que cursan con demencia.

Alzheimer's disease (AD) is a neurodegenerative condition characterized by progressive cognitive decline and memory loss, and is the most common form of dementia. Amyloid plaques with neurofibrillary tangles are a neuropathological hallmark of AD that produces synaptic dysfunction and culminates later in neuronal loss. Amyloid PET is a useful, available and non-invasive technique that provides in vivo information about the cortical amyloid burden. In the latest revised criteria for the diagnosis of AD biomarkers were defined and integrated: pathological and diagnostic biomarkers (increased retention on fibrillar amyloid PET or decreased Aß1-42 and increased T-Tau or P-Tau in CSF) and neurodegeneration or topographical biomarkers (temporoparietal hypometabolism on 18F-FDG PET and temporal atrophy on MRI). Recently specific recommendations have been created as a consensus statement on the appropriate use of the imaging biomarkers, including amyloid PET: early-onset cognitive impairment/dementia, atypical forms of AD, mild cognitive impairment with early age of onset, and to differentiate between AD and other neurodegenerative diseases that occur with dementia. Amyloid PET is also contributing to the development of new therapies for AD, as well as in research studies for the study of other neurodegenerative diseases that occur with dementia where the deposition of Aß amyloid is involved in its pathogenesis. In this paper, we review some general concepts and study the use of amyloid PET in depth and its relationship with neurodegenerative diseases and other diagnostic techniques.

Nuevos tiempos para la neuroimagen de Medicina Nuclear en España: ¿de dónde partimos? / A new era for Nuclear Medicine neuroimaging in Spain: Where do we start from in Spain?

Objetivo. conocer la situación de los estudios de neuroimagen de Medicina Nuclear que se realizaron en España en el año 2013 y primer trimestre del 2014, con el fin de definir las actividades del grupo de trabajo de Neuroimagen de la Sociedad Española de Medicina Nuclear e Imagen Molecular (SEMNIM). Material y métodos. Se diseñó un cuestionario de 14 preguntas dividido en 3 partes: características de los servicios (equipamiento y profesionales involucrados), tipo de exploraciones e indicaciones clínicas y métodos de evaluación. El cuestionario se remitió a los 166 servicios de Medicina Nuclear que figuraban en la secretaría de la Sociedad Española de Medicina Nuclear e Imagen Molecular. Resultados. Respondieron a la encuesta un total de 54 centros distribuidos entre todas las comunidades autónomas. La mayoría de los centros realizaron entre 300 y 800 exploraciones de neuroimagen al año, representando más de 25 exploraciones al mes. La media de equipos por servicio era de 3, teniendo la mitad de ellos equipos PET/TC y SPECT/TC. Las exploraciones realizadas con más frecuencia son la SPECT cerebral con 123I-FP-CIT, seguida de la SPECT cerebral de perfusión y de la PET con 18F-FDG, siendo las indicaciones clínicas más frecuentes los estudios de deterioro cognitivo seguidos por los de trastornos del movimiento. Para la evaluación de las pruebas la mayoría de los centros utilizaron únicamente la valoración visual, en la valoración cuantitativa la cuantificación por regiones de interés fue la más utilizada. Conclusiones. Los resultados reflejan cuál fue la actividad clínica del año 2013 y primer trimestre del 2014, siendo las indicaciones principales los estudios de deterioro cognitivo y trastorno del movimiento. La variabilidad en la evaluación de los estudios PET y la colaboración con los especialistas clínicos que demandan las exploraciones de neuroimagen de Medicina Nuclear son algunos de los retos que debemos afrontar en los próximos años (AU)

Objective. To determine the status of neuroimaging studies of Nuclear Medicine in Spain during 2013 and first quarter of 2014, in order to define the activities of the neuroimaging group of the Spanish Society of Nuclear Medicine and Molecular Imaging (SEMNIM). Material and methods. A questionnaire of 14 questions was designed, divided into 3 parts: characteristics of the departments (equipment and professionals involved); type of scans and clinical indications; and evaluation methods. The questionnaire was sent to 166 Nuclear Medicine departments. Results. A total of 54 departments distributed among all regions completed the questionnaire. Most departments performed between 300 and 800 neuroimaging examinations per year, representing more than 25 scans per month. The average pieces of equipment were three; half of the departments had a PET/CT scanner and SPECT/CT equipment. Scans performed more frequently were brain SPECT with 123I-FP-CIT, followed by brain perfusion SPECT and PET with 18F-FDG. The most frequent clinical indications were cognitive impairment followed by movement disorders. For evaluation of the images most sites used only visual assessment, and for the quantitative assessment the most used was quantification by region of interest. Conclusions. These results reflect the clinical activity of 2013 and first quarter of 2014. The main indications of the studies were cognitive impairment and movement disorders. Variability in the evaluation of the studies is among the challenges that will be faced in the coming years (AU)

A new era for Nuclear Medicine neuroimaging in Spain: Where do we start from in Spain? / Nuevos tiempos para la neuroimagen de Medicina Nuclear en España: ¿de dónde partimos?

OBJECTIVE: To determine the status of neuroimaging studies of Nuclear Medicine in Spain during 2013 and first quarter of 2014, in order to define the activities of the neuroimaging group of the Spanish Society of Nuclear Medicine and Molecular Imaging (SEMNIM). MATERIAL AND METHODS: A questionnaire of 14 questions was designed, divided into 3 parts: characteristics of the departments (equipment and professionals involved); type of scans and clinical indications; and evaluation methods. The questionnaire was sent to 166 Nuclear Medicine departments. RESULTS: A total of 54 departments distributed among all regions completed the questionnaire. Most departments performed between 300 and 800 neuroimaging examinations per year, representing more than 25 scans per month. The average pieces of equipment were three; half of the departments had a PET/CT scanner and SPECT/CT equipment. Scans performed more frequently were brain SPECT with 123I-FP-CIT, followed by brain perfusion SPECT and PET with 18F-FDG. The most frequent clinical indications were cognitive impairment followed by movement disorders. For evaluation of the images most sites used only visual assessment, and for the quantitative assessment the most used was quantification by region of interest. CONCLUSIONS: These results reflect the clinical activity of 2013 and first quarter of 2014. The main indications of the studies were cognitive impairment and movement disorders. Variability in the evaluation of the studies is among the challenges that will be faced in the coming years.

Machine learning models for the differential diagnosis of vascular parkinsonism and Parkinson's disease using [(123)I]FP-CIT SPECT.

PURPOSE: The study's objective was to develop diagnostic predictive models using data from two commonly used [(123)I]FP-CIT SPECT assessment methods: region-of-interest (ROI) analysis and whole-brain voxel-based analysis. METHODS: We included retrospectively 80 patients with vascular parkinsonism (VP) and 164 patients with Parkinson's disease (PD) who underwent [(123)I]FP-CIT SPECT. Nuclear-medicine specialists evaluated the scans and calculated bilateral caudate and putamen [(123)I]FP-CIT uptake and asymmetry indices using BRASS software. Statistical parametric mapping (SPM) was used to compare the radioligand uptake between the two diseases at the voxel level. Quantitative data from these two methods, together with potential confounding factors for dopamine transporter availability (sex, age, disease duration and severity), were used to build predictive models following a tenfold cross-validation scheme. The performance of logistic regression (LR), linear discriminant analysis and support vector machine (SVM) algorithms for ROI data, and their penalized versions for SPM data (penalized LR, penalized discriminant analysis and SVM), were assessed. RESULTS: Significant differences were found in the ROI analysis after covariate correction between VP and PD patients in [(123)I]FP-CIT uptake in the more affected side of the putamen and the ipsilateral caudate. Age, disease duration and severity were also found to be informative in feeding the statistical model. SPM localized significant reductions in [(123)I]FP-CIT uptake in PD with respect to VP in two specular clusters comprising areas corresponding to the left and right striatum. The diagnostic predictive accuracy of the LR model using ROI data was 90.3 % and of the SVM model using SPM data was 90.4 %. CONCLUSION: The predictive models built with ROI data and SPM data from [(123)I]FP-CIT SPECT provide great discrimination accuracy between VP and PD. External validation of these methods is necessary to confirm their applicability across centres.

Neuroimagen funcional en el diagnóstico de pacientes con síndrome parkinsoniano: actualización y recomendaciones para el uso clínico / Functional neuroimaging in the diagnosis of patients with Parkinsonism: Update and recommendations for clinical use

Las técnicas de neuroimagen funcional se han utilizado tradicionalmente en la investigación de los pacientes que presentan un síndrome parkinsoniano. Sin embargo, la aparición de radiofármacos comerciales junto a la disponibilidad de equipos de tomografía por emisión de fotón único (SPECT) y más recientemente de la tomografía por emisión de positrones (PET), han permitido su empleo rutinario en la práctica clínica. Precisamente el desarrollo y grado de evidencia clínica alcanzado por los biomarcadores de neuroimagen durante las 2 últimas décadas ha conllevado que progresivamente se estén incluyendo en los criterios clínicos de diagnóstico de enfermedades neurodegenerativas que cursan con un síndrome parkinsoniano. No obstante, la diversidad de radiofármacos que permiten evaluar la funcionalidad de las vías anatómicas involucradas en la neurodegeneración presente en los diferentes síndromes parkinsonianos (vía nigroestriatal dopaminérgica, actividad neuronal de los ganglios basales y la corteza, inervación simpática miocárdica), junto a las técnicas de neuroimagen (gammagrafía, SPECT y PET) han originado cierta controversia con respecto a la indicación de las pruebas de neuroimagen como exploración complementaria. En esta revisión realizada por un panel de expertos en medicina nuclear y neurología se analizan las técnicas de neuroimagen funcional disponibles haciendo especial énfasis en las consideraciones prácticas del diagnóstico de pacientes con un síndrome parkinsoniano de origen incierto y la valoración de la progresión de la enfermedad de Parkinson (AU)

Functional Neuroimaging has been traditionally used in research for patients with different Parkinsonian syndromes. However, the emergence of commercial radiotracers together with the availability of single photon emission computed tomography (SPECT) and, more recently, positron emission tomography (PET) have made them available for clinical practice. Particularly, the development of clinical evidence achieved by functional neuroimaging techniques over the past two decades have motivated a progressive inclusion of several biomarkers in the clinical diagnostic criteria for neurodegenerative diseases that occur with Parkinsonism. However, the wide range of radiotracers designed to assess the involvement of different pathways in the neurodegenerative process underlying Parkinsonian syndromes (dopaminergic nigrostriatal pathway integrity, basal ganglia and cortical neuronal activity, myocardial sympathetic innervation), and the different neuroimaging techniques currently available (scintigraphy, SPECT and PET), have generated some controversy concerning the best neuroimaging test that should be indicated for the differential diagnosis of Parkinsonism. In this article, a panel of nuclear medicine and neurology experts has evaluated the functional neuroimaging techniques emphazising practical considerations related to the diagnosis of patients with uncertain origin parkinsonism and the assessment Parkinson’s disease progression (AU)

Utilidad de la tomografía de emisión de fotón único-tomografía computarizada en la biopsia selectiva del ganglio centinela en pacientes con melanoma / Utility of single photon emission computed tomography-computed tomography in selective sentinel lymph node biopsy in patients with melanoma

Objetivo: Evaluar la aportación de la linfogammagrafía con SPECT-TAC en la biopsia selectiva del ganglio centinela (BSGC) en pacientes con melanoma. Material y métodos: Estudio prospectivo (julio de 2009 a octubre de 2010) incluyendo 63 pacientes diagnosticados de melanoma (32 hombres y 31 mujeres), con edad media de 55 años y criterios de inclusión de BSGC. La localización de los melanomas fue: 28 en el tronco, 5 en la cabeza y el cuello, 16 en los miembros superiores y 17 en los miembros inferiores. Tres pacientes presentaban 2 melanomas. Se realizó linfogammagrafía preoperatoria tras la inyección pericicatricial/perilesional de 74 MBq de nanocoloide de albúmina humana marcada con99mTc, obteniéndose imágenes planares precoces, estudio tardío de cuerpo completo, imágenes sectoriales y SPECT-TAC de la zona de interés. Se compararon los hallazgos de la gammagrafía planar y la SPECT-TAC. Resultados: El ganglio centinela (GC) fue localizado mediante las imágenes planares en 62/63 (98%) pacientes. La SPECT-TAC localizó el GC en los 63 pacientes (100%). El número de GC detectados con SPECT-TAC fue superior al estudio planar en 27 pacientes. El estudio SPECT-TAC aportó información adicional (cambio de localización y/o precisión de la misma en GC de ubicación incierta) en 14/63 (22,2%) pacientes, implicando cambios en el abordaje quirúrgico y en la estadificación ganglionar. Conclusión: La SPECT-TAC detecta mayor número de GC que la gammagrafía planar, siendo más relevante su aportación en los melanomas de tronco y cabeza y en los de cuello. En un 22% modificó la localización del GC respecto a los hallazgos de la gammagrafía planar, facilitando un correcto abordaje quirúrgico (AU)

Objective: To assess the contribution of SPECT-CT lymphoscintigraphy in selective sentinel lymph node biopsy (SLNB) in patients with newly diagnosed malignant melanoma. Material and methods: A prospective study was made between July 2009 and October 2010. It included 63 patients diagnosed with melanoma (32 men and 31 women) with mean age of 55 years (range: 25–88) and inclusion criteria for SLNB. The melanomas were located as follows: 28 in trunk, 5 in head and neck, 16 in upper limbs and 17 in lower limbs. Three patients had two melanomas. Preoperative lymphoscintigraphy was performed after pericicatricial/perilesional injection of 74 MBq of 99mTc-labeled nanocolloid human serum albumin, obtaining early planar images, late whole body study and sectorial images and SPEC-CT in the area of interest. Planar scintigraphy findings were compared with SPECT-CT. Results: The sentinel node (SN) was localized by planar imaging in 62/63 (98%) patients. SPECT-CT study located the SN in all the patients with a detection rate of 100%. The number of SNs detected with SPECT-CT was higher than that with the planar study in 27 patients. The SPECT-CT provided additional information (change in location and/or in its accuracy in the localization of location uncertain SN) in 14/63 (22.2%) patients, involving changes in the surgical approach and lymph node staging. Conclusion: SPECT-CT detects a higher number of SN than planar lymphoscintigraphy in patients with melanoma. Its contribution is more relevant in the melanomas located on the trunk, head and neck. SPECT-CT modified the SN location by 22% compared to planar scan findings, facilitating a correct surgical approach (AU)

[Functional neuroimaging in the diagnosis of patients with Parkinsonism: Update and recommendations for clinical use]. / Neuroimagen funcional en el diagnóstico de pacientes con síndrome parkinsoniano: actualización y recomendaciones para el uso clínico.

Functional Neuroimaging has been traditionally used in research for patients with different Parkinsonian syndromes. However, the emergence of commercial radiotracers together with the availability of single photon emission computed tomography (SPECT) and, more recently, positron emission tomography (PET) have made them available for clinical practice. Particularly, the development of clinical evidence achieved by functional neuroimaging techniques over the past two decades have motivated a progressive inclusion of several biomarkers in the clinical diagnostic criteria for neurodegenerative diseases that occur with Parkinsonism. However, the wide range of radiotracers designed to assess the involvement of different pathways in the neurodegenerative process underlying Parkinsonian syndromes (dopaminergic nigrostriatal pathway integrity, basal ganglia and cortical neuronal activity, myocardial sympathetic innervation), and the different neuroimaging techniques currently available (scintigraphy, SPECT and PET), have generated some controversy concerning the best neuroimaging test that should be indicated for the differential diagnosis of Parkinsonism. In this article, a panel of nuclear medicine and neurology experts has evaluated the functional neuroimaging techniques emphazising practical considerations related to the diagnosis of patients with uncertain origin parkinsonism and the assessment Parkinson's disease progression.

[Utility of single photon emission computed tomography-computed tomography in selective sentinel lymph node biopsy in patients with melanoma]. / Utilidad de la tomografía de emisión de fotón único-tomografía computarizada en la biopsia selectiva del ganglio centinela en pacientes con melanoma.

OBJECTIVE: To assess the contribution of SPECT-CT lymphoscintigraphy in selective sentinel lymph node biopsy (SLNB) in patients with newly diagnosed malignant melanoma. MATERIAL AND METHODS: A prospective study was made between July 2009 and October 2010. It included 63 patients diagnosed with melanoma (32 men and 31 women) with mean age of 55 years (range: 25-88) and inclusion criteria for SLNB. The melanomas were located as follows: 28 in trunk, 5 in head and neck, 16 in upper limbs and 17 in lower limbs. Three patients had two melanomas. Preoperative lymphoscintigraphy was performed after pericicatricial/perilesional injection of 74MBq of (99m)Tc-labeled nanocolloid human serum albumin, obtaining early planar images, late whole body study and sectorial images and SPECT-CT in the area of interest. Planar scintigraphy findings were compared with SPECT-CT. RESULTS: The sentinel node (SN) was localized by planar imaging in 62/63 (98%) of patients. SPECT-CT study located the SN in all the patients with a detection rate of 100%. The number of SNs detected with SPECT-CT was higher than with the planar study in 27 patients. The SPECT-CT provided additional information (change in location and/or in its accuracy in the localization of location uncertain SN) in 14/63 (22.2%) patients, involving changes in the surgical approach and lymph node staging. CONCLUSION: SPECT-CT detects a higher number of SN than planar lymphoscintigraphy in patients with melanoma. Its contribution is more relevant in the melanomas located on the trunk, head and neck. SPECT-CT modified the SN location by 22% compared to planar scan findings, facilitating a correct surgical approach.

Elaboración de una plantilla de SPM para la normalización de imágenes de SPECT con 123I-Ioflupano / Elaboration of the SPM template for the standardization of SPECT images with 123I-Ioflupane

Objetivo. El SPM (statistical parametric mapping, mapas estadísticos paramétricos) es un procedimiento de análisis ampliamente utilizado para la normalización de imágenes funcionales. El propósito de este trabajo es elaborar una plantilla (template) para la normalización de imágenes SPECT con 123I-Ioflupano (DaTSCAN®; GE Healthcare), no disponible en SPM5, y su validación respecto a otros métodos de cuantificación. Material y métodos. Para la elaboración del template seleccionamos retrospectivamente los estudios SPECT de 26 sujetos sin evidencias de degeneración nigroestriatal, con distribución de edad similar a la de los pacientes que se incluyen en la práctica habitual de nuestro servicio: 2 sujetos < 35 años (7,6%), 9 entre 35-65 años (34,6%) y 15 > 65 años (57,7%). Todos los estudios fueron normalizados con el template-T1, disponible en SPM5, obteniendo una imagen promedio del valor para cada vóxel. Para la validación analizamos 60 pacientes: 30 con enfermedad de Parkinson idiopática (EPi) con afectación del hemicuerpo derecho (66,83 ± 12,20 años) y 30 pacientes con temblor esencial (TE) (67,27 ± 8,33 años). Se compararon los índices de captación específica (ICE) de las distintas regiones estriatales, obtenidos tras la normalización de las imágenes con nuestro template y aplicando un mapa de VOIs semiautomatizado creado en Analyze v9.0 (©BIR, Mayo Clinic), con otros 2 métodos de cuantificación: a) ajuste manual de un mapa de ROIs elaborado en Analyze, y b) mediante un método semicuantitativo automatizado (HERMES-BRASS) que realiza normalización y aplicación de un mapa de VOIs. Resultados. No observamos diferencias estadísticamente significativas en la capacidad discriminatoria EPi/TE entre los 3 métodos analizados (p < 0,001). La correlación de los ICE tras la normalización con nuestro template fue mayor con la obtenida por el método b) (R > 0,871; p < 0,001). En los pacientes con EPi esta diferencia fue más acusada. Conclusiones. Nuestro estudio demuestra la eficacia de nuestro template de SPM para SPECT con 123I-Ioflupano, obtenido a partir de la normalización con el template-T1 (AU)

Purpose: Statistical parametric mapping (SPM) is a widely used produced for normalization of functional images. This study has aimed to develop a normalization template of 123I-Ioflupane SPECT-imaging DaTSCAN®, GE Healthcare), not available in SPM5, and to validate it compared to other quantification methods. Material and methods: In order to write the template we retrospectively selected 26 subjects who had no evidence of nigrostriatal degeneration and whose age distribution was similar to that of the patients in the usual practice of our Department: 2 subjects (7.6%) were < 35 years, 9 between 35-65 years (34.6%) and 15 > 65 years (57.7%). All the studies were normalized with the T1-template available in SPM5 and an average image of the value was obtained for each voxel. For validation we analyzed 60 patients: 30 with idiopathic Parkinson’s disease patients (iPD) with right involvement (66.83 ± 12.20 years) and 30 with essential tremor patients (ET) (67.27 ± 8.33 years). Specific uptake rates (SUR) of different striatal regions were compared after image normalization with our template and the application of a semiautomated VOIs-map created with Analyze v9.0 (©BIR, Mayo Clinic), against two quantification methods: a) manual adjustment of a ROIs-map drawn in Analyze, and b) semi-automated method (HERMES-BRASS) with normalization and implementation of VOIs-map. Results: No statistically significant differences in the iPD/ET discriminatory capacity between the three methods analyzed were observed (p < 0,001). The correlation of SUR after normalization with our «template» was higher than that obtained by method b) (R > 0,871, p < 0,001). This difference was greater in patients with PD. Conclusions: Our study demonstrates the efficacy of our SPM «template» for 123I-Ioflupane SPECT-imaging, obtained from normalization with «T1-template» (AU)

[Elaboration of the SPM template for the standardization of SPECT images with 123I-Ioflupane]. / Elaboración de una plantilla de SPM para la normalización de imágenes de SPECT con 123I-Ioflupano.

PURPOSE: Statistical parametric mapping (SPM) is a widely used produced for normalization of functional images. This study has aimed to develop a normalization template of (123)I-Ioflupane SPECT-imaging DaTSCAN(®), GE Healthcare), not available in SPM5, and to validate it compared to other quantification methods. MATERIAL AND METHODS: In order to write the template we retrospectively selected 26 subjects who had no evidence of nigrostriatal degeneration and whose age distribution was similar to that of the patients in the usual practice of our Department: 2 subjects (7.6%) were < 35 years, 9 between 35-65 years (34.6%) and 15 > 65 years (57.7%). All the studies were normalized with the T1-template available in SPM5 and an average image of the value was obtained for each voxel. For validation we analyzed 60 patients: 30 with idiopathic Parkinson's disease patients (iPD) with right involvement (66.83±12.20 years) and 30 with essential tremor patients (ET) (67.27±8.33 years). Specific uptake rates (SUR) of different striatal regions were compared after image normalization with our template and the application of a semiautomated VOIs-map created with Analyze v9.0 ((©)BIR, Mayo Clinic), against two quantification methods: a) manual adjustment of a ROIs-map drawn in Analyze, and b) semi-automated method (HERMES-BRASS) with normalization and implementation of VOIs-map. RESULTS: No statistically significant differences in the iPD/ET discriminatory capacity between the three methods analyzed were observed (p<0,001). The correlation of SUR after normalization with our «template¼ was higher than that obtained by method b) (R>0,871, p<0,001). This difference was greater in patients with PD. CONCLUSIONS: Our study demonstrates the efficacy of our SPM «template¼ for (123)I-Ioflupane SPECT-imaging, obtained from normalization with «T1-template¼.

Apolipoproteína e4 en la demencia con cuerpos de Lewy / Apolipoprotein e4 in dementia with Lewy bodies

Introducci¨®n. Existe una fuerte asociaci¨®n entre el alelo¦Å4 de la apolipoprote¨ªna E (APOE) y enfermedad de Alzheimer(EA), constituyendo este alelo un factor de riesgopara padecer esta enfermedad. Su asociaci¨®n con la demenciacon cuerpos de Lewy (DCL) es objeto de controversia. Enla DCL la presencia de APOE4 se ha relacionado con unamayor carga de placas seniles y degeneraci¨®n neurofibrilar.M¨¦todo. Estudio de casos y controles en el que se determin¨®el genotipo APOE mediante la t¨¦cnica de reacci¨®nen cadena de la polimerasa (PCR) modificada de Wenhamen 306 pacientes diagnosticados de EA probable, criteriosNINCDS-ADRDA, 58 casos de DCL probable, criterios de consensode McKeith et al. (1996), todos ellos con SPECT con 123IFP-CIT patol¨®gico, y 80 controles normales (CN) de edad y distribuci¨®npor sexos similares.Resultados. La frecuencia de alelos fue la siguiente:DCL ¦Å4: 16%; ¦Å3: 75%; ¦Å2: 9%; EA ¦Å4: 32%; ¦Å3: 67%; ¦Å2:1%; CN ¦Å4: 12%; ¦Å3: 83%; ¦Å2: 5%. En los tres grupos la distribuci¨®nde alelos en ambos sexos fue similar.Conclusiones. En la DCL la frecuencia de ¦Å4 (16%) esmuy inferior a la de la EA (32%) y muy pr¨®xima a la cifra delos CN (12%). Teniendo en cuenta que la presencia de alteracionesmorfopatol¨®gicas tipo Alzheimer en la DCL, fundamentalmentedegeneraci¨®n neurofibrilar, se correlacionainversamente con la presencia de signos parkinsonianos, esposible que este grupo represente a las formas puras de laenfermedad, aunque la falta de comprobaci¨®n neuropatol¨®gicano permite confirmar esta hip¨®tesis (AU)

Introduction. There is a strong association betweenthe ¦Å4 allele of apolipoprotein E (APOE) and Alzheimer¡¯sdisease (AD). This converts this allele into a risk factorfor the development of AD. The association between APOE4and dementia with Lewy bodies (DLB) is under discussion.In DLB, the presence of APOE4 has been related with a greateramount of senile plaques and neurofibrillary tangles.Method. This is a case-control study in which the APOEgenotype was determined using the modified PCR techniqueof Wenham in 306 patients with diagnosis of probably AD,NINCDS-ADRDA criteria, 58 cases of probably DLB, McKeithet al. consensus criteria (1996), all of them with SPECT withpathological 123I-FP-CIT and 80 normal controls (NC) havingsimilar age and gender distribution.Results. The frequency of alleles was: DLB group ¦Å4:16%; ¦Å3: 75%; ¦Å2: 9%; AD: ¦Å4: 32%; ¦Å3: 67%; ¦Å2: 1%;and in the normal control group: ¦Å4: 12%; ¦Å3: 83%; ¦Å2:5%. The percentage of alleles in both genders was similarin the three groups.Conclusions. APOE4 percentage in DLB group (16%)was lower than in AD group (32 %), and similar to thecontrol group (12 %). Considering that the presence ofmorphopathological Alzheimer type alterations in DBL,essentially neurofibrillary tangles, is inversely correlatedwith the presence of Parkinsonian signs, this group mayrepresent pure forms of the disease, although the lack ofneuropathological demonstration does not make it possibleto confirm this hypothesis (AU)

[Apolipoprotein E4 in dementia with Lewy bodies]. / Apolipoproteína e4 en la demencia con cuerpos de Lewy.

INTRODUCTION: There is a strong association between the e4 allele of apolipoprotein E (APOE) and Alzheimer's disease (AD). This converts this allele into a risk factor for the development of AD. The association between APOE4 and dementia with Lewy bodies (DLB) is under discussion. In DLB, the presence of APOE4 has been related with a greater amount of senile plaques and neurofibrillary tangles. METHOD: This is a case-control study in which the APOE genotype was determined using the modified PCR technique of Wenham in 306 patients with diagnosis of probably AD, NINCDS-ADRDA criteria, 58 cases of probably DLB, McKeith et al. consensus criteria (1996), all of them with SPECT with pathological 123I-FP-CIT and 80 normal controls (NC) having similar age and gender distribution. RESULTS: The frequency of alleles was: DLB group epsilon4: 16%; epsilon3: 75%; epsilon2: 9%; AD: epsilon4: 32%; epsilon3: 67%; epsilon2: 1%; and in the normal control group: epsilon4: 12%; epsilon3: 83%; epsilon2: 5%. The percentage of alleles in both genders was similar in the three groups. CONCLUSIONS: APOE4 percentage in DLB group (16%) was lower than in AD group (32%), and similar to the control group (12%). Considering that the presence of morphopathological Alzheimer type alterations in DBL, essentially neurofibrillary tangles, is inversely correlated with the presence of Parkinsonian signs, this group may represent pure forms of the disease, although the lack of neuropathological demonstration does not make it possible to confirm this hypothesis.

Imagen de neurotransmisión dopaminérgica en los síndromes parkinsonianos / Dopaminergic neurotransmission image in Parkinsonian syndromes

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Practice of nuclear medicine in Spain.

This survey presents the results of a poll sent to all Spanish nuclear medicine departments between July 1999 and March 2000, with the aim of clarifying the current situation of nuclear medicine in Spain. This survey is believed to be the first of its kind, and it is anticipated that the data will be of assistance to health authorities in ensuring that the needs of the population with regard to nuclear medicine facilities are met.

Generation of LAK cells in vitro in patients with acute leukemia.

The in vitro stimulation of lymphocytes with interleukin-2 (IL-2) generates lymphokine-activated killer (LAK) cells with tumoricidal potential. In this work we studied the cytolytic capacity of LAK cells in 51 acute leukemia patients in complete remission (CR) after chemotherapy (CT), in 24 acute leukemia patients who had undergone autologous bone marrow transplantation (ABMT), and in a control group of 44 normal donors. In the normal donor control group the effect of non-IL-2-activated peripheral blood mononuclear cells (PBMC) against blast cells was always lower than 10% lysis, which we have taken as a lower limit for positive results. In 95% of post-CT patients, the lytic effect of PBMC was negative. LAK cells produced positive results in 82% of normal donors and in 37.5% of post-CT patients. The effect of PBMC against K562, i.e. natural killer (NK) activity, in post-CT patients as well as in post-ABMT patients was reduced in comparison with the average for normal donors. LAK cells from 25% of post-CT patients had no notable activity against K562 or Raji, nor was there any positive effect against autologous blast cells. In the rest (75%), one-half generated positive activity. We did not observe any correlation between lytic activity in PBMCs or in LAK cells, nor did we observe significant differences between lytic activity in patients with acute lymphoblastic leukemia (ALL) and those with acute myeloblastic leukemia (AML), or between patients who had undergone CT and those receiving ABMTs. These results support the use of IL-2 as a treatment against minimal residual leukemia.