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.

[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.

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.

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.

[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.