Study of the inferior colliculus in patients with schizophrenia by magnetic resonance spectroscopy.

INTRODUCTION. Previous studies have suggested morphometric and functional abnormalities in the inferior colliculus in patients with schizophrenia. Auditory hallucinations are one of the central symptoms in schizophrenia. In this complex and multidimensional event both attention and emotion are thought to play a key role. AIM. To study metabolic changes in the inferior colliculus, a nucleus integrated in the auditory pathway, in patients with schizophrenia and the possible relationship with auditory hallucinations. SUBJECTS AND METHODS. Magnetic resonance spectroscopic imaging studies were performed in 30 right-handed patients with chronic schizophrenia (19 of them with auditory hallucinations) and 28 controls. A magnetic resonance spectroscopic imaging 2D slice was acquired and the voxels representative of both inferior colliculi were selected. N-acetylaspartate (NAA), creatine (Cr) and choline (Cho) peak areas were measured. RESULTS. The patients with schizophrenia showed a NAA/Cr significant reduction in the right inferior colliculus compared to the control subjects. The metabolic data in the right inferior colliculus were correlated with emotional auditory hallucinations items. CONCLUSIONS. The contribution of the inferior colliculus on neural underpinnings of auditory hallucinations is particularly relevant for the right inferior colliculus and is centered on attention-emotional component of this symptom.

TITLE: Estudio del coliculo inferior de pacientes con esquizofrenia mediante espectroscopia de resonancia magnetica.Introduccion. Algunos estudios anteriores en pacientes con esquizofrenia han sugerido alteraciones morfometricas y funcionales en el coliculo inferior. Las alucinaciones auditivas son uno de los sintomas centrales en la esquizofrenia. Se piensa que en este evento complejo y multidisciplinar, tanto la atencion como la emocion desempeñan un papel clave. Objetivo. Estudiar los cambios metabolicos en el coliculo inferior, un nucleo integrado en la via auditiva, en pacientes con esquizofrenia y su posible relacion con las alucinaciones auditivas. Sujetos y metodos. Se llevaron a cabo estudios de espectroscopia de resonancia magnetica en 30 pacientes diestros con esquizofrenia cronica (19 de ellos con alucinaciones auditivas) y 28 controles. Se adquirio una secuencia 2D de espectroscopia de resonancia magnetica y se seleccionaron los voxeles representativos de ambos coliculos inferiores. Se calculo el area de los picos de N-acetilaspartato (NAA), creatina (Cr) y colina (Co). Resultados. Los pacientes con esquizofrenia mostraron una reduccion significativa de NAA/Cr en el coliculo inferior derecho comparados con los sujetos control. Los datos metabolicos en el coliculo inferior derecho se correlacionaron con los items emocionales de las alucinaciones auditivas. Conclusiones. La contribucion del coliculo inferior a las bases neuronales de las alucinaciones auditivas es particularmente relevante para el coliculo inferior derecho y se centra en el componente atencional-emocional de este sintoma.

Complementariedad de la espectroscopía univóxel y la imágen de espectroscopía multivóxel obtenidas mediante bobina de cuadratura para la detección del carcinoma de próstata / Quadrature coils for magnetic resonance spectroscopy in the detection of prostate cancer: Single voxel acquisition does not improve the diagnostic accuracy of multivoxel images

Objetivo. Demostrar la viabilidad de la bobina de cuadratura para la detección del cáncer de próstata mediante espectroscopía univóxel e imágen multivóxel. Material y métodos. Se evaluaron 23 pacientes con sospecha de carcinoma de próstata, con niveles del antígeno especifico de próstata superior a 4ng/ml, (media 12±8ng/ml), independientemente del tacto rectal, estudiados en un equipo de RM de 1,5T con la bobina de cuadratura. Se adquirieron imágenes potenciadas en T2 e imágenes de espectroscopía. También se adquirieron estudios univóxel en aquellas zonas donde la imágen T2 o la imágen multivóxel estaban alteradas. Se realizó un control metodológico de espectroscopía con una disolución patrón de citrato. Resultados. Con la imágen espectroscópica y un punto de corte [(Co+Cr)/Cit] de 1,40 en el vóxel único se alcanzan unos valores de sensibilidad del 92%, especificidad del 55%, predictivo negativo del 86% y predictivo positivo del 69%. Con un punto de corte de 0,75, la especificidad disminuye discretamente (45%). La relación [(Co+Cr)/Cit] calculada para el volumen único obtenido del área más anormal en el T2 y en los cortes de espectroscopía multivóxel no mostró diferencias significativas entre tejidos no tumorales y carcinomas (ANOVA, p=0,1), aunque se observó una clara tendencia a aumentar el cociente con la hiperplasia y la degeneración neoplásica. Conclusión. La bobina de cuadratura permite obtener imágen multivóxel y espectros univóxel con una calidad técnica y clínicamente aceptables. El empleo de la espectroscopía univóxel no mejora la rentabilidad diagnóstica de la espectroscopía multivóxel y la imágen T2(AU)

Objective. To determine the viability of quadrature coils for detecting prostate cancer using single voxel and multivoxel spectroscopy images. Material and methods. We used a quadrature coil on a 1.5T MR scanner to evaluate 23 patients with suspected prostate cancer and prostate specific antigen levels greater than 4ng/ml (mean 12±8ng/ml), independently of findings at digital rectal examination. We acquired T2-weighted images and MR spectroscopy images. We also acquired single voxel studies in areas in which the T2-weighted images or the multivoxel images were altered. We used a citrate solution to verify the spectroscopic calibration. Results. Using spectroscopy images and a (Co+Cr)/Cit cutoff of 1.40 in single voxel spectroscopy, we achieved a sensitivity of 92%, specificity of 55%, a negative predictive value of 86%, and a positive predictive value of 69%. Using a cutoff of 0.75 decreased specificity slightly (45%). The (Co+Cr)/Cit ratio calculated for the single volume obtained from the most abnormal area in the T2-weighted images and in the multivoxel spectroscopy slices was not significantly different between cancerous and non-cancerous tissues (ANOVA, p=0.1), although there was a clear trend toward increased coefficients with hyperplasia and neoplastic degeneration. Conclusion. The quadrature coil enables multivoxel and single voxel spectroscopic images of clinically and technically acceptable quality to be obtained. Using single voxel spectroscopy does not improve the diagnostic performance of multivoxel spectroscopy and T2-weighted images(AU)

[Quadrature coils for magnetic resonance spectroscopy in the detection of prostate cancer: single voxel acquisition does not improve the diagnostic accuracy of multivoxel images]. / Complementariedad de la espectroscopía univóxel y la imágen de espectroscopía multivóxel obtenidas mediante bobina de cuadratura para la detección del carcinoma de próstata.

OBJECTIVE: To determine the viability of quadrature coils for detecting prostate cancer using single voxel and multivoxel spectroscopy images. MATERIAL AND METHODS: We used a quadrature coil on a 1.5T MR scanner to evaluate 23 patients with suspected prostate cancer and prostate specific antigen levels greater than 4ng/ml (mean 12±8ng/ml), independently of findings at digital rectal examination. We acquired T2-weighted images and MR spectroscopy images. We also acquired single voxel studies in areas in which the T2-weighted images or the multivoxel images were altered. We used a citrate solution to verify the spectroscopic calibration. RESULTS: Using spectroscopy images and a (Co+Cr)/Cit cutoff of 1.40 in single voxel spectroscopy, we achieved a sensitivity of 92%, specificity of 55%, a negative predictive value of 86%, and a positive predictive value of 69%. Using a cutoff of 0.75 decreased specificity slightly (45%). The (Co+Cr)/Cit ratio calculated for the single volume obtained from the most abnormal area in the T2-weighted images and in the multivoxel spectroscopy slices was not significantly different between cancerous and non-cancerous tissues (ANOVA, p=0.1), although there was a clear trend toward increased coefficients with hyperplasia and neoplastic degeneration. CONCLUSION: The quadrature coil enables multivoxel and single voxel spectroscopic images of clinically and technically acceptable quality to be obtained. Using single voxel spectroscopy does not improve the diagnostic performance of multivoxel spectroscopy and T2-weighted images.

Ex vivo high resolution magic angle spinning metabolic profiles describe intratumoral histopathological tissue properties in adult human gliomas.

In gliomas one can observe distinct histopathological tissue properties, such as viable tumor cells, necrotic tissue or regions where the tumor infiltrates normal brain. A first screening between the different intratumoral histopathological tissue properties would greatly assist in correctly diagnosing and prognosing gliomas. The potential of ex vivo high resolution magic angle spinning spectroscopy in characterizing these properties is analyzed and the biochemical differences between necrosis, high cellularity and border tumor regions in adult human gliomas are investigated. Statistical studies applied on sets of metabolite concentrations and metabolite ratios extracted from 52 high resolution magic angle spinning recordings coming from patients with different grades of glial tumors show a strong correlation between the histopathological tissue properties and the considered metabolic profiles, regardless of the malignancy grade. The results are in agreement with the pathology obtained by the histopathological examination that succeeded the high resolution magic angle spinning measurements. The metabolite concentration set can better differentiate between the considered histopathological tissue properties compared to the ratios. Representative reference tissue models describing the metabolic behavior are extracted for characterizing the intratumoral tissue properties. The proposed metabolic profiles reflect that the metabolites behavior is interconnected, and typical biochemical patterns emerge for each histopathological tissue property.

Non-negative blind source separation techniques for tumor tissue typing using HR-MAS signals.

Given High Resolution Magic Angle Spinning (HR-MAS) signals from several glioblastoma tumor subjects, the goal is to differentiate between tumor tissue types by separating the different sources that contribute to the profile of each spectrum. Blind source separation techniques are applied for obtaining characteristic profiles for necrosis, high cellular tumor and border tumor tissue, and providing the contribution (abundance) of each tumor tissue to the profile of the spectra. The problem is formulated as a non-negative source separation problem. We illustrate the effectiveness of the proposed methods and we analyze to which extent the dimension of the input space could influence the performance by comparing the results on the full magnitude signals and on dimensionally reduced spaces.

Comparative metabolic profiling of paediatric ependymoma, medulloblastoma and pilocytic astrocytoma.

Brain tumours are the most common solid tumours in children and a major cause of childhood mortality. The most common paediatric brain tumours include ependymomas, cerebellar astrocytomas and medulloblastomas. These brain tumours are highly heterogeneous regarding their histology, prognosis and therapeutic response. Subtle biochemical changes can be detected in intact tissues by High-Resolution Proton Magnetic Angle Spinning Spectroscopy (HR-MAS) revealing the status of tumour microheterogeneity and metabolic alterations before they are morphologically detectable. In this study, we present metabolic profiles by HR-MAS of 20 intact tissue samples from paediatric brain tumours. Tumour types include ependymoma, medulloblastoma and pilocytic astrocytoma. The metabolic characterization of paediatric brain tumour tissue by HR-MAS spectroscopy provided differential patterns for these tumours. The metabolic composition of the tumour tissue was highly consistent with previous in vivo and ex vivo studies. Some resonances detected in this work and not previously observed by in vivo spectroscopy also show potential in determining tumour type and grade (fatty acids, phenylalanine, glutamate). Overall, this work suggests that the additional information obtained by NMR metabolic profiling applied to tissue from paediatric brain tumours may be useful for assessing tumour grade and determining optimum treatment strategies.

Proton magnetic resonance spectroscopy imaging in the study of human brain cancer.

Magnetic resonance spectroscopic imaging (MRSI) is a non-invasive imaging technique that provides metabolic information on brain tumor. This biochemical information can be processed and presented as density maps of several metabolites, among them N-acetylaspartate (marker of neuronal viability), choline (marker of membrane turnover), creatine (related to the energy state of the cells), myo-Inositol (exclusively found in astrocytes), lipids and lactate (observed in necrosis and other pathological processes) which mean relevant information in the context of brain tumors. Thus, this technique is a multiparametrical molecular imaging method that can complete the magnetic resonance imaging (MRI) study enabling the detection of biochemical patterns of different features and aspects of brain tumors. In this article, the role of MRSI as a molecular imaging technique to provide biochemical information on human brain tumors is reviewed. The most frequent questions and situations in the study of human brain tumors in clinical settings will be considered, as well as the distinction of neoplastic lesions from non neoplastic, the tumor type identification, the study of heterogeneity and infiltration of normal appearing white matter and the therapy following with detection of side effects. The great amount of data in MRSI acquisition compared to the single voxel techniques requires the use of automated methods of quantification, but the possibility to obtain self-reference in the non-affected areas allows different strategies for data handling and interpretation, as presented in the literature. The combination of MRSI with other physiological MRI techniques and positron emission tomography is also included in this review.

Spectroscopic metabolomic abnormalities in the thalamus related to auditory hallucinations in patients with schizophrenia.

OBJECTIVE: Previous studies have found neurochemical abnormalities in thalamic nuclei in patients with schizophrenia. These abnormalities have been associated with information processing deficiencies and symptom formation. There are no metabolic spectroscopy studies in patients with schizophrenia attending to auditory hallucinations. The aim of the present study is to explore metabolic Magnetic Resonance Spectroscopy (MRS) ratio differences in the thalamus between schizophrenic patients with and without auditory hallucinations and control subjects. METHODS: MRS studies (MRI 1.5 T unit) were performed in 49 patients with schizophrenia (30 with auditory hallucinations and 19 without auditory hallucinations) and 37 controls. (1)H MRS imaging was used to acquire 2 transverse slices (TR/TE 2700/272 ms, region of interest 110 x 100 x 23 mm). In the quantitative analysis four elements of volume (9.2 x 9.2 x 23 x 4 mm), added into one spectrum representative of each thalamus, were chosen in the slice passing through the main body of the thalamus. The areas of metabolites were integrated with the jMRUI program. RESULTS: The patients with schizophrenia had significantly lower bilateral NAA/Cho ratios when compared with healthy subjects. There was also a lower NAA/Cho ratio in the right thalamus in patients with auditory hallucinations compared to patients without auditory hallucinations and control subjects. Significant correlations were found between metabolic ratios and BPRS, PANSS and PSYRATS scores, age of onset of auditory hallucinations, and age of subjects. CONCLUSIONS: Choline and NAA ratio abnormalities determined by thalamic spectroscopy may be related to the pathogenesis of auditory hallucinations in patients with schizophrenia.

[Total brain T2-hyperintense lesion-volume and the axonal damage in the normal-appearing white matter of brainstem in early lapsing-remitting multiple sclerosis]. / Relación entre el volumen lesional cerebral total en resonancia magnética secuencia T2 y el daño neuroaxonal en la sustancia blanca aparentemente normal del tronco del encéfalo en la esclerosis múltiple remitente-recurrente.

AIM: To evaluate the relationship between the total brain T2-hyperintense lesion volume (TBT2LV) and the axonal damage in the normal-appearing white matter of brainstem measured by 1H-MRS in a group of early relapsing-remitting multiple sclerosis patients. SUBJECTS AND METHODS: 40 relapsing-remitting multiple sclerosis patients and ten sex- and age-matched healthy subjects were prospectively studied for two years. T2-weighted MR and 1H-MRS imaging were acquired at time of recruitment and at year two. The TBT2LV was calculated with a semiautomatic program; N-acetylaspartate (NAA), creatine (Cr) and choline (Cho) resonances areas were integrated with jMRUI program and the ratios were calculated for four volume elements that represented the brainstem. RESULTS: At basal study we obtained an axonal loss (as a decrement of NAA/ Cho ratio) in the group of patients compared with controls (p = 0.017); this axonal loss increased at the second year of the follow-up for patients (NAA/Cho decrease, p = 0.004, and NAA/Cr decrease, p = 0.002) meanwhile control subjects had no significant metabolic changes. Higher lesion load was correlated with a poor clinical outcome, being the correlation between the basal TBT2LV and the Expanded Disability Status Scale at second year (r = 0.299; p = 0.05). Besides, axonal loss was not homogeneous for all multiple sclerosis patients, being stronger in the subgroup of patients with high basal TBT2LV (p = 0.043; ANOVA). CONCLUSION: Our data suggest that axonal damage is early in multiple sclerosis and higher in patients high basal TBT2LV, suggesting a possible relationship between these two phenomena.

Relación entre el volumen lesional cerebral total en resonancia magnética secuencia T2 y el daño neuroaxonal en la sustancia blanca aparentemente normal del tronco del encéfalo en la esclerosis múltiple remitente-recurrente

Analizar mediante espectroscopia de protón el daño neuroaxonal en la sustancia blanca aparentementenormal del tronco del encéfalo y su relación con el volumen lesional cerebral total en T2 (VLCT2) medido por resonancia magnética, en pacientes con esclerosis múltiple remitente-recurrente. Sujetos y métodos. Estudio longitudinal prospectivo comparativo a dos años de las variaciones en la concentración de N-acetilaspartato (NAA), creatina (Cr) y colina (Co), medidas por espectroscopia de protón, en 40 pacientes afectos de esclerosis múltiple remitente-recurrente y 10 personas sanas ajustadas por sexo y edad. Los metabolitos se calcularon mediante el programa jMRUI en cuatro volúmenes de interés representadosen el troncoencéfalo, y el VLCT2, con un programa semiautomático. Resultados. El estudio basal mostró daño neuroaxonal (expresado como un menor cociente NAA/Co, p = 0,017) en el grupo de pacientes frente a los controles. El daño axonal se incrementó significativamente a los dos años sólo en el grupo de pacientes (descenso del cociente NAA/Co, p =0,004, y NAA/Cr, p = 0,002). Un mayor volumen lesional basal se correlacionó con una peor evolución clínica, representada por la Expanded Disability Status Scale a los 2 años (r = 0,299; p = 0,05). La intensidad del daño neuroaxonal no fue homogénea en todos los pacientes, siendo mayor en el subgrupo de pacientes con VLCT2 basal superior (p = 0,043; ANOVA). Conclusión.Los resultados sugieren que el daño neuroaxonal aparece precozmente en la esclerosis múltiple, que es progresivo y que se relaciona al menos parcialmente con el volumen lesional cerebral

To evaluate the relationship between the total brain T2-hyperintense lesion volume (TBT2LV) and the axonaldamage in the normal-appearing white matter of brainstem measured by 1H-MRS in a group of early relapsing-remitting multiple sclerosis patients. Subjects and methods. 40 relapsing-remitting multiple sclerosis patients and ten sex- and agematchedhealthy subjects were prospectively studied for two years. T2-weighted MR and 1H-MRS imaging were acquired attime of recruitment and at year two. The TBT2LV was calculated with a semiautomatic program; N-acetylaspartate (NAA), creatine (Cr) and choline (Cho) resonances areas were integrated with jMRUI program and the ratios were calculated for four volume elements that represented the brainstem. Results. At basal study we obtained an axonal loss (as a decrement of NAA/Cho ratio) in the group of patients compared with controls (p = 0.017); this axonal loss increased at the second year of the follow-up for patients (NAA/Cho decrease, p = 0.004, and NAA/Cr decrease, p = 0.002) meanwhile control subjects had no significant metabolic changes. Higher lesion load was correlated with a poor clinical outcome, being the correlation betweenthe basal TBT2LV and the Expanded Disability Status Scale at second year (r = 0.299; p = 0.05). Besides, axonal loss was not homogeneous for all multiple sclerosis patients, being stronger in the subgroup of patients with high basal TBT2LV (p = 0.043; ANOVA). Conclusion. Our data suggest that axonal damage is early in multiple sclerosis and higher in patients highbasal TBT2LV, suggesting a possible relationship between these two phenomena

Axonal loss is progressive and partly dissociated from lesion load in early multiple sclerosis.

OBJECTIVE: To assess the relationship between the spectroscopically measured axonal damage in the normal-appearing white matter of the brainstem, the total brain T2-hyperintense lesion volume (T2LV), and disability in patients with early relapsing-remitting multiple sclerosis (RRMS). METHODS: Forty-three RRMS patients and 10 sex- and age-matched healthy controls were prospectively studied for 2 years. T2-weighted magnetic resonance (MR) images and proton MR spectroscopy were acquired at the time of recruitment and at year 2. Brainstem was considered, where large tracts join together, as a suitable region to detect early axonal damage. The T2LV was calculated with a semiautomatic program; N-acetylaspartate (NAA), creatine (Cr), and choline (Cho) resonances areas were integrated with the jMRUI program, and the ratios were calculated for the sum of the volume elements represented at brainstem. RESULTS: The basal NAA/Cho ratio was significantly decreased in patients compared with controls. After 2-year follow-up, there was a decrease in the NAA/Cho (-9%; p = 0.002) and NAA/Cr (-13%; p = 0.001) ratios, and an increase in the T2LV (19%; p = 0.043) in multiple sclerosis patients, whereas control subjects had no significant metabolic changes. Significant NAA/Cr ratio decreases were observed in both patients, with and without relapses, whereas T2LV only increased in patients with relapses. The final Expanded Disability Status Scale (EDSS) score correlated with T2LV at baseline, but no significant correlations were found between metabolic values, T2LV change, or EDSS score over the study period. CONCLUSIONS: Our data reveal an early and progressive axonal damage in relapsing-remitting multiple sclerosis. Axonal loss and T2 lesion volume seem to be at least partly dissociated processes in early stages of the disease.

Demencias: contribución diagnóstica de la imagen y de la espectroscopia de resonancia magnética de protón / Dementias: diagnostic contribution of imaging and proton magnetic resonance spectroscopy

Introducción. El objetivo es establecer la complementariedad de imagen y espectroscopia de resonancia magnética de protón (1HERM) en el diagnóstico global de demencia Alzheimer (DA) o demencia vascular (DV). Métodos. Se estudiaron 168 pacientes con deterioro cognitivo comprendiendo DA, DV, deterioro cognitivo leve (DCL) y depresión mayor. Todos se exploraron con resonancia magnética (RM) cerebral y 1HERM, adquiriendo espectros del cíngulo posterior y circonvolución temporal media derecha. Los metabolitos analizados fueron N-acetilaspartato (NAA), mio-inositol (Mi) y colina (Co) con la creatina (Cr) como metabolito de referencia para las relaciones Co/Cr, Mi/Cr y NAA/Cr. Las alteraciones en imagen y espectroscopia fueron graduadas de 0 a 4, así como la combinación promedio de las mismas, obteniéndose curvas ROC y SROC, con el criterio de área bajo la curva como capacidad discriminativa (Az). Resultados. La combinación de imagen de RM y 1HERM mejoró significativamente el diagnóstico de DA (Az global: 0,722, frente a RM Az: 0,624; p= 0,003). Sin embargo, la combinación de RM y 1HERM no mejoró el diagnóstico de DV. La curva SROC para el diagnóstico global de demencia mostró una Az de 0,6658, con sensibilidad y especificidad de 0,67 y 0,65, respectivamente. Conclusiones. La combinación de las dos técnicas de RM (imagen y espectroscopia) mejoró el diagnóstico de DA frente a la imagen aislada, mejorando el diagnóstico de forma estadísticamente significativa. Se necesitan mayores estudios para la mejora de la clasificación de la DV. Las diferencias metabólicas encontradas mediante ERM entre pacientes pueden ser útiles para diferenciar el deterioro cognitivo

Introduction. The objetive is analyze the complementarity between 1H magnetic resonance spectroscopy (MRS) and magnetic resonance (MR) imaging in the global diagnosis of Alzheimer's disease (AD) or vascular dementia (VD). Methods. We studied 168 patients with cognitive impairment from AD, VD, mild cognitive impairment (MCI) and major depression. All patients were evaluated by brain MR imaging and MRS using two sample volumes localized at right medial temporal gyrus and posterior parietal gyrus. Metabolites analyzed were N-acetylaspartate (NAA), myo-Inositol (mI), Choline (Cho) and creatine (Cr), as standard references for obtaining the Co/Cr, mI/Cr and NAA/Cr ratios. Imaging and spectroscopy alterations were graded from 0 to 4 and the average of both was used to draw ROC and SROC curves. Area under ROC curve (Az) was used as a measure of discriminative ability. Results. Combination of MR imaging and MRS significantly improved AD diagnosis (Global Az: 0.722 vs. MR imaging Az: 0.624; p: 0.003). However, the combination of MR imaging and MRS did not improve VD diagnosis. SROC curve obtained for the diagnosis of global dementia was Az: 0.6658 with 0.67 sensitivity and 0.65 specificity. Conclusions. Combination of both MR techniques significantly improved AD diagnosis versus MR imaging alone. More studies are needed to enhance VD classification. Metabolic data found by MRS can be useful to differentiate cognitive impairment

[Dementias: diagnostic contribution of imaging and proton magnetic resonance spectroscopy]. / Demencias: contribución diagnóstica de la imagen y de la espectroscopia de resonancia magnética de protón.

INTRODUCTION: The objective is analyze the complementarity between 1H magnetic resonance spectroscopy (MRS) and magnetic resonance (MR) imaging in the global diagnosis of Alzheimer's disease (AD) or vascular dementia (VD). METHODS: We studied 168 patients with cognitive impairment from AD, VD, mild cognitive impairment (MCI) and major depression. All patients were evaluated by brain MR imaging and MRS using two sample volumes localized at right medial temporal gyrus and posterior parietal gyrus. Metabolites analyzed were N-acetylaspartate (NAA), myo-Inositol (mI), Choline (Cho) and creatine (Cr), as standard references for obtaining the Co/Cr, mI/Cr and NAA/Cr ratios. Imaging and spectroscopy alterations were graded from 0 to 4 and the average of both was used to draw ROC and SROC curves. Area under ROC curve (Az) was used as a measure of discriminative ability. RESULTS: Combination of MR imaging and MRS significantly improved AD diagnosis (Global Az: 0.722 vs. MR imaging Az: 0.624; p: 0.003). However, the combination of MR imaging and MRS did not improve VD diagnosis. SROC curve obtained for the diagnosis of global dementia was Az: 0.6658 with 0.67 sensitivity and 0.65 specificity. CONCLUSIONS: Combination of both MR techniques significantly improved AD diagnosis versus MR imaging alone. More studies are needed to enhance VD classification. Metabolic data found by MRS can be useful to differentiate cognitive impairment

[Cognitive impairment: classification by proton magnetic resonance spectroscopy and the contributions of conventional magnetic resonance imaging]. / Deterioro cognitivo: clasificación mediante espectroscopia de resonancia magnética de protón y contribución de la imagen convencional.

OBJECTIVE: To analyze the diagnostic accuracy of proton magnetic resonance spectroscopy (1H MRS) in patients with cognitive impairment and to establish the usefulness of complementary information provided by conventional magnetic resonance imaging (MRI). MATERIAL AND METHODS: 64 patients with cognitive impairment, including Alzheimer's disease (AD) (n=31), vascular dementia (n=6), mild cognitive impairment (MCI) (n=9), and major depression (n=18), were studied. All patients underwent cerebral MRI and single-volume 1H MRS using two echo times (TE, 31 and 136 ms) in the posterior cingulate gyrus and right temporal lobe. The metabolites analyzed were N-acetylaspartate (NAA), myo-Inositol (mI), choline (Ch), and creatine (Cr), and the ratios of Ch/Cr, mI/Cr, NAA/mI and NAA/Cr were calculated. In order to differentiate among the different types of cognitive impairment, the alterations in imaging and spectroscopy findings were graded from 0 to 4, as was the mean combination of the two, and then ROC curves were obtained. RESULTS: Statistically significant differences were found between the spectra of patients with dementia (AD and vascular dementia) and those without dementia (MCI and depression) in the posterior cingulate gyrus. The NAA/mI ratio yielded the best area under the ROC curve, with the best sensitivity (82.5%) and specificity (72.7%) in the diagnosis of AD. The NAA/mI and mI/Cr quotients differentiated between the four degenerative pathologies causing the cognitive impairment. The combination of MRI and 1H MRS significantly improved the accuracy of the diagnosis of AD. CONCLUSIONS: The metabolic differences found among patients with cognitive impairment using 1H MRS can be useful for differentiating AD, vascular dementia, MCI, and depression. The combination of spectroscopy and MRI findings is useful in the diagnosis of AD.

MRS as endogenous molecular imaging for brain and prostate tumors: FP6 project "eTUMOR".

Molecular imaging has become during the last years in an important tool for supporting cancer diagnosis and prognosis. PET and SPECT are the most common molecular imaging techniques, although very promising and specific biological molecular agent contrast for CT and MRI are being recently developed. However, the above imaging techniques require exogenous contrast agents and usually a sole molecular image can be obtained at once. On the contrary, in vivo magnetic resonance spectroscopy (MRS), in particular 1H MRS can simultaneously provide several molecular images using endogenous metabolites. In addition to biochemical spatial information from molecular imaging spectroscopy, MRS can also provide average metabolite profile of the selected affected tissue region. Initially MRS, especially 1H MRS, was extensively applied to complete and improve the diagnosis and prognosis of central nervous system (CNS) pathologies, in particular brain tumors. However, during the last years the MRS applications have been extent to the diagnosis of different very common cancer types such as breast, prostate, colon carcinoma, and ovarian, among others. Likewise, MRS has been also used for lymph node assessment. In this contribution, the added value of MRS for the diagnosis, prognosis, and treatment selection of two different, important types of cancer: (1) brain tumors and (2) prostate, will be presented and discussed. Brain tumors are the leading cause of death in children under 15, and although in adults, brain cancers are proportionately less common than other cancers, it is a devastating disease with high mortality. There is a great need to increase our understanding of brain tumor biology to improve diagnosis and to develop new treatments. 1H MRS is currently the only noninvasive method that can be used to investigate molecular profile of brain tumors and also provide molecular images, more than six in one acquisition, of the distribution of chemicals in a tumor, which are also generally heterogeneous. A summary of the applications of 1H MRS to the in vivo diagnosis and prognosis of brain tumors will be presented. In addition, examples of metabolite limits, infiltration and high cellularity location for neurosurgery applications by MRS molecular images will be shown. Likewise, new ex vivo methods of studying the detailed biochemistry of tumor biopsies as metabolomic (high resolution magic angle spinning [HR-MAS]) and transcriptomic (DNA microarrays) will be discussed as complementary to in vivo MRS (FP6 European project eTUMOR). A preliminary comparison between molecular images from PET and 1H MRS will be also presented. Finally, the application of 1H MRS to the improvement of prostate diagnosis and prognosis, the second leading cause of cancer death, will also discussed, with particular attention to the location cancer contribution from MRS molecular images.

Deterioro cognitivo: clasificación mediante espectroscopia de resonancia magnética de protón y contribución de la imagen convencional / Cognitive impairment: classification by proton magnetic resonance spectroscopy and the contributions of conventional magnetic resonance imaging

Objetivo. Analizar la eficacia diagnóstica de la espectroscopia de resonancia magnética de protón (1H ERM) en pacientes con deterioro cognitivo y establecer la complementariedad de la información de imagen de resonancia magnética (RM) mediante curvas ROC. Material y métodos. Se estudian 64 pacientes con deterioro cognitivo, incluyendo enfermedad de Alzheimer (EA) (N = 31), demencia vascular (N = 6), deterioro cognitivo leve (DCL) (N = 9) y depresión mayor (N = 18). Todos se exploraron con RM cerebral y 1H ERM usando dos tiempos de eco (TE, 31 y 136 ms) con volumen único en la circonvolución cingular posterior y lóbulo temporal derecho. Los metabolitos analizados fueron N-acetilaspartato (NAA), mio-Inositol (mI), colina (Co), y creatina (Cr) calculando las relaciones Co/Cr, mI/Cr, NAA/mI y NAA/Cr. Para diferenciar entre las distintas formas de deterioro cognitivo, las alteraciones en imagen y en espectroscopia fueron graduadas de 0 a 4, así como la combinación promedio de las mismas, obteniéndose posteriormente curvas ROC. Resultados. Se obtuvieron diferencias estadísticamente significativas entre los espectros de pacientes con demencia (EA y demencia vascular) y los que no presentaban demencia (DCL y depresión) en la circunvolución cingular posterior. La relación NAA/mI proporcionó la mejor área bajo la curva ROC con la mayor sensibilidad (82,5%) y especificidad (72,7%) en el diagnóstico de EA. Los cocientes NAA/mI y mI/Cr diferenciaron entre las cuatro patologías degenerativas de deterioro cognitivo. La combinación de imagen de RM y ERM mejoró significativamente el diagnóstico de la EA. Conclusiones. Las diferencias metabólicas encontradas mediante ERM entre pacientes con deterioro cognitivo pueden ser útiles para diferenciar la EA, demencia vascular, DCL y depresión. La combinación de espectroscopia e imagen de RM es útil para el diagnóstico de la EA

Objective. To analyze the diagnostic accuracy of proton magnetic resonance spectroscopy (1H MRS) in patients with cognitive impairment and to establish the usefulness of complementary information provided by conventional magnetic resonance imaging (MRI). Material and methods: 64 patients with cognitive impairment, including Alzheimer's disease (AD) (n=31), vascular dementia (n=6), mild cognitive impairment (MCI) (n=9), and major depression (n=18), were studied. All patients underwent cerebral MRI and single-volume 1H MRS using two echo times (TE, 31 and 136 ms) in the posterior cingulate gyrus and right temporal lobe. The metabolites analyzed were N-acetylaspartate (NAA), myo-Inositol (mI), choline (Ch), and creatine (Cr), and the ratios of Ch/Cr, mI/Cr, NAA/mI and NAA/Cr were calculated. In order to differentiate among the different types of cognitive impairment, the alterations in imaging and spectroscopy findings were graded from 0 to 4, as was the mean combination of the two, and then ROC curves were obtained. Results. Statistically significant differences were found between the spectra of patients with dementia (AD and vascular dementia) and those without dementia (MCI and depression) in the posterior cingulate gyrus. The NAA/mI ratio yielded the best area under the ROC curve, with the best sensitivity (82.5%) and specificity (72.7%) in the diagnosis of AD. The NAA/mI and mI/Cr quotients differentiated between the four degenerative pathologies causing the cognitive impairment. The combination of MRI and 1H MRS significantly improved the accuracy of the diagnosis of AD. Conclusions. The metabolic differences found among patients with cognitive impairment using 1H MRS can be useful for differentiating AD, vascular dementia, MCI, and depression. The combination of spectroscopy and MRI findings is useful in the diagnosis of AD

Cognitive impairment: classification by 1H magnetic resonance spectroscopy.

1H magnetic resonance spectroscopy (MRS) allows accurate and non-invasive in vivo metabolic study, and is a useful tool for the diagnosis of different forms of dementias. Cognitive impairment pathologies have been almost exclusively studied with MRS by comparison with healthy without a global comparison amongst Alzheimer disease (AD), vascular dementia, mild cognitive impairment (MCI) and major depression patients with cognitive impairment. Whereas decrease of N-acetylaspartate (NAA) and increase myo-Inositol (mI) at different brain locations by 1H MRS are common features of AD, Choline (Cho) alterations have been inconclusive. In our study, 64 patients with cognitive impairment were evaluated by 1H MRS using two echo times (31 and 136 ms). There were statistical differences between dementia (AD and vascular dementia) and non-dementia (MCI and depression) spectra at posterior cingulate gyrus. Cho/Cr, mI/Cr and NAA/Cr have been valuables for the differentiation amongst the different cognitive impairment entities. NAA/mI provides the best area under the ROC curve with the highest sensitivity (82.5%) and specificity (72.7%) in diagnosing AD. NAA/mI and mI/Cr ratios differed amongst the four cognitive impairment degenerative pathologies. Metabolic MRS differences found amongst patients with cognitive impairment entities can be useful to differentiate between AD, vascular dementia, MCI and depression.

Conformational and structural analysis of the equilibrium between single- and double-strand beta-helix of a D,L-alternating oligonorleucine.

Alternating sequences of D and L residues in peptides are directly related to the formation of several kinds of regular helical conformations usually called beta-helices. The major feature of these structures is that they can be associated with the transmembrane ion-conducting channel activity in some natural antibacterial peptides. The study of alternating D,L synthetic peptides is critical to understand how factors such as surrounding media, main chain length, type of side chain and terminal groups, among others, can determine the adoption of a specific kind of beta-helix. Early studies pointed out that the peptides Boc-(D-NLeu-L-NLeu)(6)-D-MeNLe-L-Nl-D-Nl-L-Nl-OMe (Boc: tert-butyloxycarbonyl) and Boc-L-Nle-(D-Nle-L-Nle)(5)-D-MeNle-L-Nle-D-Nle-L-Nle-OMe adopt in chloroform a unique detectable conformation single beta(4.4)- and double beta(5.6) upward arrow downward arrow -helix, respectively. The influence of terminal groups on the final stable conformation of N-formylated peptides has been studied in this work. The initial basic NMR data analysis of a synthetic alternating D,L-oligopeptide with ten norleucines, N-methylated on the residue 7 and having HCO- and -OMe as terminal groups clearly indicates the coexistence of two different conformations in equilibrium. NMR data and molecular dynamics calculations point to a dimeric antiparallel beta-helix structure beta(5.6) upward arrow downward arrow for the main conformation. On the other hand, NMR data suggest a single beta-helix structure beta(4.4) for the second conformation. Finally, a thermodynamic analysis of the equilibrium between both conformations has been carried out by one-dimensional NMR measurements at ten different temperatures. The temperature at which 50% of dimer conformation is dissociated is 319 K. In addition, the dimer-monomer equilibrium curve obtained shows a DeltaG>0 for the whole range of studied temperatures, and its behavior can be considered similar to the thermodynamic denaturation protein processes.

Evidence of Wallerian degeneration in normal appearing white matter in the early stages of relapsing-remitting multiple sclerosis: a HMRS study.

OBJECTIVE: Wallerian degeneration in normal appearing white matter in early relapsing-remitting multiple sclerosis (RRMS), and its correlation with the number of relapses and disease duration. Background Recent pathological studies have demonstrated Wallerian degeneration in normal appearing white matter (NAWM) in multiple sclerosis (MS), in established RRMS, and in chronic MS. However, the presence of Wallerian degeneration early in the disease and its correlation with relapse and with disease duration has not been studied. METHODS: We performed proton magnetic resonance spectroscopic imaging in 21 MS patients, and 4 healthy controls, age and gender matched, aged under 45 years, with a maximum of 4 years since first bout, and an EDSS score of less than 3.0. N-acetyl-aspartate (NAA) (an index of axonal integrity) was measured in the NAWM from the pons and the cerebellar peduncles. RESULTS: We observed that the NAA levels were abnormally low in the NAWM in the early RRMS patients (p = 0.04, Student's t-test). The decrease in the NAA concentration correlated with disease duration in the two areas studied (p = 0.03 for pons and p = 0.04 for cerebellar peduncle); and with the number of previous relapses (Pearson's correlation = -0.582, p < 0.002). CONCLUSION: Wallerian degeneration measured by the NAA concentration at pons and cerebellar peduncles is present early in the disease and correlates with the number of relapses and disease duration.