Reduced NAA in the thalamus and altered membrane and glial metabolism in schizophrenic patients detected by 1H-MRS and tissue segmentation

Functional and structural abnormalities in the thalamus as well as a generalized phospholipid membrane disorder have been implicated in the pathogenesis of schizophrenic psychosis. To determine whether thalamic neuronal abnormalities and altered membrane-associated metabolites can be detected in schizophrenic patients, we used in vivo proton magnetic resonance spectroscopy (1H-MRS) in 32 acutely-ill, medicated schizophrenic patients and 17 age-matched controls. Thalamic and white matter metabolite concentrations (myo-inositol (mI), choline-containing compounds (Cho), total creatine (Cr) and N-acetylaspartate (NAA)) were estimated and corrected for atrophy (CSF) and gray and white matter contributions (GM, WM) by use of image-based voxel segmentation. Thalamic NAA was significantly reduced in schizophrenic patients, whereas Cho and mI were significantly increased in the parietal white matter. White matter Cr was significantly elevated in patients and correlated positively with the brief psychiatric rating scores (BPRS). Regional metabolite levels were inversely associated with GM and WM content reaching significance for mI and Cr in the thalamus and Cho and NAA in the white matter. Reduced NAA in the left thalamus of schizophrenic patients confirms and extends previous spectroscopic data and agrees well with histologic and imaging findings of reduced neuronal density and volume. Elevated Cho in line with 31P-MRS studies suggests increased myelin degradation thus further supporting a generalized membrane disorder in schizophrenic patients. In addition, we demonstrate the need to correct metabolite concentrations for regional tissue composition in studies employing patients with altered brain morphology.     

Selective reduction of N-acetylaspartate in medial temporal and parietal lobes in AD

BACKGROUND: Both AD and normal aging cause brain atrophy, limiting the ability of MRI to distinguish between AD and age-related brain tissue loss. MRS imaging (MRSI) measures the neuronal marker N-acetylaspartate (NAA), which could help assess brain change in AD and aging. OBJECTIVES: To determine the effects of AD on concentrations of NAA, and choline- and creatine-containing compounds in different brain regions and to assess the extent NAA in combination with volume measurements by MRI improves discrimination between AD patients and cognitively normal subjects. METHODS: Fifty-six patients with AD (mean age: 75.6 +/- 8.0 years) and 54 cognitively normal subjects (mean age: 74.3 +/- 8.1 years) were studied using MRSI and MRI. RESULTS: NAA concentration was less in patients with AD compared with healthy subjects by 21% (p < 0.0001) in the medial temporal lobe and by 13% to 18% (p < 0.003) in parietal lobe gray matter (GM), but was not changed significantly in white matter and frontal lobe GM. In addition to lower NAA, AD patients had 29% smaller hippocampi and 11% less cortical GM than healthy subjects. Classification of AD and healthy subjects increased significantly from 89% accuracy using hippocampal volume alone to 95% accuracy using hippocampal volume and NAA together. CONCLUSION: In addition to brain atrophy, NAA reductions occur in regions that are predominantly impacted by AD pathology.     

MRS in relation to hippocampal volume in the oldest old

The MRS brain metabolite ratio N-acetylaspartate (NAA)/myo-inositol (mI) is reported to be decreased in AD. MRS was used to study medial temporal and parietal regions in 60 cognitively healthy subjects older than 85 years. Subjects with small hippocampal volumes, a putative risk factor for dementia, had significantly lower NAA/mI in parietal and temporal lobes compared with other subjects. Neuropsychological tests and APOE genotype did not correlate with MRS ratios. MRS measures are candidate biomarkers for dementia risk.     

Regional myo-inositol concentration in mild cognitive impairment Using 1H magnetic resonance spectroscopic imaging

The goal was to assess regional patterns of metabolite abnormalities in mild cognitive impairment (MCI) and Alzheimer disease (AD) patients using proton magnetic resonance spectroscopy imaging at 1.5 Tesla. Fourteen MCI, 17 AD, and 16 healthy control (HC) subjects were studied. MCI was associated with higher myo-inositol (mIn) concentration in right parietal white matter compared with HC and lower mIn levels in frontal white matter compared with AD. AD was associated with higher mIn concentration in frontal and parietal white matter compared with HC. N-acetylaspartate (NAA) concentration of white matter was similar in all groups, whereas NAA concentration of gray matter showed a trend toward lower values in the right parietal lobe in AD compared with MCI and HC. A mIn increase in white matter in absence of significant NAA reduction suggests that mIn is a more robust and sensitive marker of white matter pathology in AD and MCI than NAA. Furthermore, the dissociation between mIn and NAA alterations in white matter could provide important information regarding the role of glial and neuronal damage in MCI and AD.     

Proton magnetic resonance spectroscopy in frontotemporal dementia

This study of frontotemporal dementia (FTD) was carried out to determine whether MR spectroscopy can provide an in vivo marker for the neuronal loss and gliosis that occur in this condition. We compared spectra in frontal and temporal regions known to be affected early in the course of the disease with spectra in the parietal lobe that is spared until late stages of FTD. We were interested in the relative concentrations of two compounds, NAA (a marker of neuronal integrity) and mI (a marker of gliosis), expressed as ratios to creatine (a relatively stable brain constituent). MR spectroscopy was performed on the temporal, parietal, and anterior cingulate cortices of five patients with the established semantic dementia form of FTD, two patients with the frontal form of FTD and 13 age matched controls. Structural MRI and neuropsychometry were also performed. Patients with FTD had reduced NAA/Cr in frontal and temporal, but not parietal lobes. The two patients with the frontal form of FTD had increased mI/Cr in their cingulate cortices. These data show for the first time that MR spectroscopy can reveal regionally selective abnormalities in patients with FTD. This opens up the possibility of using MR spectroscopy as a clinical tool to identify earlier presentations of the condition.     

Single-voxel proton spectroscopy using a press sequence with a 135 ms echotime: normal values

The clinical value of MR spectroscopy is now well established and this technique has been added to the current French classification of medical acts (CCAM). This paper presents a set of normal control values for 3 metabolite ratios obtained using a PRESS sequence with a TE of 135 ms at 1.5T: NAA/Cho, NAA/Cr and Cho/CR. Spectroscopy data acquisition were obtained from the following 12 anatomical regions: parieto-occipital white matter, centrum semiovale, frontal white matter, thalamus, basal ganglia, cerebellum (hemisphere, including dentate nucleus), brain stem (including pons, medulla and midbrain), anterior and posterior temporal lobe, parietal, occipital and pre-frontal cortices. The presented data allow radiologists equipped with a similar MR system to implement a clinical spectroscopy program without undergoing research protocols in order to obtain control values.     

Multimodal imaging in diagnosis of Alzheimer's disease and amnestic mild cognitive impairment: value of magnetic resonance spectroscopy, perfusion, and diffusion tensor imaging of the posterior cingulate region

The purpose of this study was to assess metabolic, perfusion, and microstructural changes within the posterior cingulate area in patients with Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) using advanced MR techniques such as: spectroscopy (MRS), perfusion weighted imaging (PWI), and diffusion tensor imaging (DTI). Thirty patients with AD (mean age 71.5 y, MMSE 18), 23 with aMCI (mean age 66 y, MMSE 27.4), and 15 age-matched normal controls (mean age 69 y, MMSE 29.5) underwent conventional MRI followed by MRS, PWI, and DTI on 1.5 Tesla MR unit. Several metabolite ratios (N-acetylaspartate [NAA]/creatine [Cr], choline [Ch]/Cr, myoinositol [mI]/Cr, mI/NAA, mI/Cho) as well as parameters of cerebral blood volume relative to cerebellum and fractional anisotropy were obtained in the posterior cingulate region. The above parameters were correlated with the results of neuropsychological tests. AD patients showed significant abnormalities in all evaluated parameters while subjects with aMCI showed only perfusion and diffusion changes in the posterior cingulate area. Only PWI and DTI measurements revealed significant differences among the three evaluated subject groups. DTI, PWI, and MRS results showed significant correlations with neuropsychological tests. DTI changes correlated with both PWI and MRS abnormalities. Of neuroimaging methods, DTI revealed the highest accuracy in diagnosis of AD and aMCI (0.95, 0.79) followed by PWI (0.87, 0.67) and MRS (0.82, 0.47), respectively. In conclusion, AD is a complex pathology regarding both grey and white matter. DTI seems to be the most useful imaging modality to distinguish between AD, aMCI, and control group, followed by PWI and MRS.     

Identification of axonal involvement in Hallervorden-Spatz disease with magnetic resonance spectroscopy

Hallervorden-Spatz disease is a neurodegenerative disorder associated with cysteine-iron complex accumulation typically seen as bilateral symmetrical hypointense signal changes in the medial globus pallidus on magnetic resonance imaging. We used magnetic resonance spectroscopy to identify and quantify neuronal damage in two siblings with Hallervorden-Spatz disease. The first patient presenting with a rapidly progressive extrapyramidal syndrome had markedly decreased N-acetylaspartate (NAA) to creatinine (Cr) ratios in the globus pallidi and the periatrial white matter. He also had increased myoinositol (mI) to creatinine (Cr) ratios implying glial proliferation in the affected regions. However the second patient who had the initial presentation of disease had normal NAA/Cr and mI/Cr ratios. These findings indicate that the quantification of NAA:Cr and mI:Cr ratios might be used to predict the extent of neuronal axonal loss and glial proliferation in patients with Hallervorden-Spatz disease respectively.     

Rasmussen's encephalitis: proton MR spectroscopy and diffusion MR findings

Rasmussen's encephalitis is a chronic inflammation of the brain that leads to progressive neurologic deficits. The condition has previously been studied by various imaging modalities including MR imaging and MR spectroscopy. We studied three patients presenting with Rasmussen's encephalitis by using proton MR spectroscopy, and diffusion-weighted MR imaging. In these patients, on diffusion-weighted MR imaging, mean apparent diffusion coefficient (ADC) value was 1.74 x 10(-3) mm(2)/sec within the parenchyma, apparently higher than that of the normal parenchyma (0.88 x 10(-3) mm(2)/sec) of a control group of five healthy subjects. Proton MR spectra were obtained with a TR value of 1,500 msec and differing TE values (135, 40, and 20 msec), and were compared with a control group of fourteen cases. In the affected regions of the brain, MR spectroscopy revealed decreased NAA, and increased Cho peaks associated with apparently decreased NAA/Cho, NAA/Cr ratios, and increased Cho/Cr ratios. Slightly increased mI peaks, and increased mI/NAA ratios were noted. A prominent lactate peak was noted in one of the patients.     

Altered white and gray matter metabolism in CADASIL: a proton MR spectroscopy and 1H-MRSI study

OBJECTIVE: Subcortical white matter hyperintensities (WMH) and small cystic lesions are the radiologic hallmark of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditary angiopathy causing stroke in young adults. To further characterize the cerebral pathology in vivo we analyzed metabolite concentrations in normal and abnormal appearing brain tissue using single and multiple voxel proton MR spectroscopy (1H-MRS and 1H-MRSI). METHODS: Twenty patients with CADASIL and 21 age-matched controls were studied with 1H-MRSI at the level of the centrum semiovale; short echo time 1H-MRS was performed in six patients (WMH) and 10 controls. LCModel fits were used to estimate absolute and relative concentrations of N:-acetylaspartate (NAA), choline-containing compounds (Cho), total creatine (Cr) within WMH, normal appearing white matter (NAWM), and cortical gray matter (GM) as well as myo-inositol (mI) and lactate in WMH. RESULTS: 1H-MRSI-Patients with CADASIL showed significantly reduced NAA, Cho, Cr, and total metabolite content (Met(tot)) in WMH and NAWM. Normalization to Met(tot) revealed that NAA/Met(tot) was reduced in all regions, whereas Cho and Cr were relatively elevated in WMH. Short echo time 1H-MRS showed decreased NAA, Cr, Met(tot), and NAA/Met(tot) and elevated mI/Met(tot) and lactate in WMH. Metabolite changes were larger in severely affected subjects. Rankin scores correlated negatively with NAA/Met(tot) (all regions) and NAA/Cho (WMH), and positively with Cho/Met(tot) (WMH) and Cr/Met(tot) (NAWM). CONCLUSION: Marked metabolic abnormalities were observed in abnormal and normal appearing white matter in patients with CADASIL. The findings suggest axonal injury, enlarged extracellular spaces, myelin loss, and gliosis. The cortical abnormalities may reflect structural damage or functional neuronal impairment secondary to white matter pathology. NAA reductions were correlated with clinical disability emphasizing the clinicopathologic relevance of axonal injury in CADASIL.     

Proton spectroscopic imaging shows abnormalities in glial and neuronal cell pools in frontal lobe epilepsy

PURPOSE: Proton magnetic resonance spectroscopic imaging (1H MRSI) can lateralize the epileptogenic frontal lobe by detecting metabolic ratio abnormalities in frontal lobe epilepsy (FLE). We used 1H MRS to lateralize and localize the epileptogenic focus, and we also sought to characterize further the metabolic abnormality in FLE. METHODS: We measured signals from N-acetyl aspartate (NAA), choline-containing compounds (Cho), and creatine + phosphocreatine (Cr) in the supraventricular brain of 14 patients with frontal or frontoparietal epilepsy and their matched controls. The supratentorial brain also was segmented into gray matter, white matter, and cerebrospinal fluid classes. Regional metabolite alterations were compared with localizing and lateralizing results from other examination modalities and with histology from three patients. RESULTS: Spectroscopy lateralized the epileptogenic focus in 10 patients in agreement with video-EEG and functional imaging. In four patients, spectroscopy showed bilateral, focal metabolic abnormality, whereas video-EEG suggested unilateral or midline abnormality. In the epileptogenic focus, Cho and Cr were increased by 23% and 14%, respectively, and NAA was decreased by 11%, suggesting metabolic disturbances both in the glial and in the neuronal cell pools. Two Taylor dysplasia lesions confirmed by histology and one with radiologic diagnosis showed high Cho and low or normal NAA, whereas two dysembryoplastic neurogenic tumors had normal Cho and low NAA. Contralateral hemisphere NAA/(Cho + Cr) was decreased in FLE, indicating diffusely altered brain metabolism. Segmentation of brain tissue did not reveal atrophic changes in FLE. CONCLUSIONS: Spectroscopy is useful in lateralizing frontoparietal epilepsy and shows promise as a "noninvasive biopsy" in epileptogenic lesions.     

Preliminary evidence for white matter metabolite differences in marijuana-dependent young men using 2D J-resolved magnetic resonance spectroscopic imaging at 4 Tesla

Chronic marijuana (MRJ) use is associated with altered cognition and mood state, altered brain metabolites, and functional and structural brain changes. The objective of this study was to apply proton magnetic resonance spectroscopic imaging (MRSI) to compare proton metabolite levels in 15 young men with MRJ dependence and 11 healthy non-using (NU) young men. Spectra were acquired at 4.0 Tesla using 2D J-resolved MRSI to resolve coupled resonances in J-space and to quantify the entire J-coupled spectral surface of metabolites from voxels containing basal ganglia and thalamus, temporal and parietal lobes, and occipital white and gray matter. This method permitted investigation of high-quality spectra for regression analyses to examine metabolites relative to tissue type. Distribution of myo-inositol (mI)/creatine (Cr) was altered in the MRJ group whereas the NU group exhibited higher mI/Cr in WM than GM, this pattern was not observed in MRJ subjects. Significant relationships observed between global mI/Cr and distribution in WM, and self-reported impulsivity and mood symptoms were also unique between MRJ and NU groups. These preliminary findings suggest that mI, and distribution of this glial metabolite in WM, is altered by MRJ use and is associated with behavioral and affective features reported by young MRJ-dependent men.     

The correlation between 1H-MR spectroscopy and clinical manifestation with tuberous sclerosis complex

Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous disease. Cortical tubers are one of the standard intracranial hallmarks of TSC, they comprise subependymal hamartomas protruding into the ventricles, cortical and white matter hamartomas, and giant cell tumors. The clinical course of TSC varies from asymptomatic to severe, with epileptic seizures and psychomotor retardation. We discuss here the correlation between clinical manifestation and features on 1H-MR spectroscopy ( 1H-MRS) of the white matter involving cortical tubers in patients with TSC. Statistical analysis of the N-acetylaspartate (NAA), choline (Cho) and myoinositol (mI)/creatinine (Cr) ratios between tubers and normal controls showed decreased NAA/Cr and increased mI/Cr ratios (P<0.05) in tubers, but no significance difference in Cho/Cr. The significance of the clinical appearance is associated with a decreased ratio of NAA/Cr in tubers with TSC. An elevated ratio of mI/Cr in tuber does not parallel the severity of the clinical features of TSC. These findings suggest that 1H-MRS may be useful for the evaluation of the clinical severity and prognostic diagnosis of TSC.     

1H-MRS evaluation of metabolism in Alzheimer's disease and vascular dementia

Proton magnetic resonance spectroscopy (1H-MRS) allows major metabolites to be measured noninvasively in defined regions of the living brain, and can detect biochemical abnormalities where conventional structural imaging appears normal. MRS can be performed in 10 min as part of a clinical MRI examination. Biochemical abnormalities in Alzheimer's Disease (AD), vascular dementia (VaD) and other primary degenerative dementias have been investigated using MRS. Characteristic and consistent abnormalities in AD are decreased N-acetyl aspartate (NAA) and elevated myo-inositol (mI) in the mesial temporal and parieto-occipital cortex. These are thought to represent neuronal loss/dysfunction and gliosis, in anatomic distributions which reflect early pathological involvement and atrophy patterns in AD. Less consistent disturbances of glutamine and glutamate (Glx) and choline-containing compounds (Cho) have also been reported. Similar changes are seen in VaD; mostly in white matter, whereas in AD they predominate in cortical grey matter. The regional distribution of grey matter involvement may differ between AD and other degenerative dementias. Hence, both the nature and anatomic distribution of metabolite abnormalities contribute to diagnostic discrimination with MRS. NAA/mI ratios from short echo time spectra of the posterior cingulate region cortex discriminate reliably between AD subjects, normal individuals and those with VaD, and provides a useful clinical test, as an adjunct to structural imaging. Elevated mI is detected in mild cognitive impairment (MCI) and quantitative metabolite measures correlate with degrees of cognitive impairment in AD; these suggest a possible role for MRS in early diagnosis and for surrogate biochemical markers for monitoring disease progression and therapeutic response.     

Brain metabolite concentration and dementia severity in Alzheimer's disease: a (1)H MRS study

OBJECTIVE: (1)H-MRS studies have shown abnormalities in brain levels of myo-inositol (mI) and N-acetyl aspartate (NAA) in AD, but the relation of these abnormalities with dementia severity was not examined. The authors sought to determine whether altered brain levels of mI and other metabolites occur in mild AD and whether they change as dementia severity worsens. METHODS: The authors used (1)H-MRS with external standards to measure absolute brain concentrations of mI, NAA, total creatine (Cr), and choline (Cho)-containing compounds in 21 subjects with AD and 17 age- and sex-matched controls in occipital and left and right parietal regions. RESULTS: Concentrations of NAA were significantly decreased, whereas mI and Cr concentrations were significantly increased in all three brain regions in subjects with AD compared with controls. Higher concentrations of mI and Cr occurred even in mild AD. A discriminant analysis of the (1)H-MRS data combined with CSF volume measurements distinguished subjects with AD, ranging from mild to severe dementia, from controls with 100% correct classification. NAA concentration, though not other metabolites, was positively correlated with Mini-Mental State Examination score. CONCLUSION: The measurements with (1)H-MRS of absolute metabolite concentrations in the neocortex showed abnormal concentrations of brain metabolites in AD; these metabolite concentrations do not necessarily correlate with disease severity. Although changes in myo-inositol and creatine occur in the early stages of AD, abnormalities of N-acetyl aspartate do not occur in mild AD but progressively change with dementia severity. Further, subjects with mild AD can be differentiated from controls with (1)H-MRS.     

Quantitative 1H MR spectroscopic imaging in early Rett syndrome

OBJECTIVE: To determine cerebral regional concentrations of N-acetyl aspartate (NAA), total choline (Cho), and total creatine (Cr) in Rett syndrome (RS) using 1H magnetic resonance spectroscopic imaging (MRSI). BACKGROUND: The biochemical defect underlying RS is unknown. Because in vivo MRSI can detect important cerebral metabolites, MRSI has a potential to reveal impairment of regional cerebral metabolism in RS noninvasively. METHODS: High-resolution, multislice 1H MRSI was carried out in 17 girls with RS. The control group consisted of nine healthy children. RESULTS: In patients with RS, average Cho concentration was 12% higher (p < 0.005) and average NAA concentration 11% lower (p < 0.0001) compared with the control group. Regional metabolic differences included significantly lower NAA concentration in the frontal gray and white matter, insula, and hippocampus in RS; no difference in regional Cho and Cr concentrations were found. A 20 to 38% higher Cho:NAA ratio in frontal and parietal gray and white matter, insular gray matter, and hippocampus (p < 0.05) and a 14 to 47% lower NAA:Cr ratio in frontal cortical gray matter, parietal and temporal white matter, insula, and putamen (p < 0.05) were found in subjects with RS compared with controls. Patients with seizures had higher average concentrations of Cho, Cr, and NAA compared with those without seizures (8-19%, p < 0.05). CONCLUSION: Metabolic impairment in RS involves both gray and white matter and particularly involves frontal and parietal lobes and the insular cortex. Loss of NAA most likely reflects reduced neuronal and dendritic tree size; increased Cho concentration may result from gliosis.     

Preliminary evidence for white matter metabolite differences in marijuana-dependent young men using 2D J-resolved magnetic resonance spectroscopic imaging at 4 Tesla

Chronic marijuana (MRJ) use is associated with altered cognition and mood state, altered brain metabolites, and functional and structural brain changes. The objective of this study was to apply proton magnetic resonance spectroscopic imaging (MRSI) to compare proton metabolite levels in 15 young men with MRJ dependence and 11 healthy non-using (NU) young men. Spectra were acquired at 4.0 Tesla using 2D J-resolved MRSI to resolve coupled resonances in J-space and to quantify the entire J-coupled spectral surface of metabolites from voxels containing basal ganglia and thalamus, temporal and parietal lobes, and occipital white and gray matter. This method permitted investigation of high-quality spectra for regression analyses to examine metabolites relative to tissue type. Distribution of myo-inositol (mI)/creatine (Cr) was altered in the MRJ group whereas the NU group exhibited higher mI/Cr in WM than GM, this pattern was not observed in MRJ subjects. Significant relationships observed between global mI/Cr and distribution in WM, and self-reported impulsivity and mood symptoms were also unique between MRJ and NU groups. These preliminary findings suggest that mI, and distribution of this glial metabolite in WM, is altered by MRJ use and is associated with behavioral and affective features reported by young MRJ-dependent men.     

Interaction of dopamine transporter and metabolite ratios underpinning the cognitive dysfunction in patients with carbon monoxide poisoning: A combined SPECT and MRS study

Cognitive dysfunction has been reported in patients with carbon monoxide (CO) poisoning. However, the underpinning mechanism remained unclear. This study examined dopamine transporter (DAT) and metabolite ratios concurrently and their relationships with cognitive dysfunction in CO poisoning. Eighteen suicide attempters with charcoal burning which results in CO poisoning and 18 age- and gender- matched normal controls were recruited. A battery of cognitive assessments including attention, memory, and executive function was administered. Each participant received one single photon emission computed tomography with ^99mTc-TRODAT for measuring striatal DAT availability and proton magnetic resonance spectroscopy to determine N-acetyl aspartate/creatine (NAA/Cr), choline-containing compounds/creatine (Cho/Cr) and myo-inositol/creatine (mI/Cr) in the left parietal white matter and mid-occipital gray matter (OGM). CO poisoning patients had significant impairments in memory and executive function. Compared to normal, CO poisoning patients had lower striatal DAT availability, lower NAA/Cr levels in both regions and higher Cho/Cr levels in both regions. In CO poisoning patients, the altered left striatal DAT availability and Cho/Cr level in OGM were significantly associated with executive dysfunction in the expected directions. Moreover, there was a significant interaction between these two imaging indices on their relationships with executive dysfunction and combination of them could adequately predict executive dysfunction in more CO poisoning cases than either alone. The current results suggested that both alterations in DAT availability and metabolite ratios might play crucial roles in executive dysfunction in CO poisoning. This research also highlights the importance of multimodal imaging approaches for studying neurotoxicity effects.     

Cerebral metabolite abnormalities in human immunodeficiency virus are associated with cortical and subcortical volumes

Cerebral metabolite disturbances occur among human immunodeficiency virus (HIV)-infected people, and are thought to reflect neuropathology, including proinflammatory processes, and neuronal loss. HIV-associated cortical atrophy continues to occur, though its basis is not well understood, and the relationship of cerebral metabolic disturbance to structural brain abnormalities in HIV has not been well delineated. We hypothesized that metabolite disturbances would be associated with reduced cortical and subcortical volumes. Cerebral volumes were measured in 67 HIV-infected people, including 10 people with mild dementia (acquired immunodeficiency syndrome [AIDS] dimentia complex [ADC] stage >1) via automated magnetic resonance imaging (MRI) segmentation. Magnetic resonance spectroscopy (MRS) was used to measure levels of cerebral metabolites N-acetylaspartate (NAA), myo-inositol (MI), choline-containing compounds (Cho), glutamate/glutamine (Glx), and creatine (Cr) from three brain regions (frontal gray matter, frontal white matter, basal ganglia). Analyses were conducted to examine the associations between MRS and cerebral volumetric measures using both absolute and relative metabolite concentrations. NAA in the mid-frontal gray matter was most consistently associated with cortical (global, frontal, and parietal), ventricular, and caudate volumes based on analysis of absolute metabolite levels, whereas temporal lobe volume was associated with basal ganglia NAA and Glx, and Cho concentrations in the frontal cortex and basal ganglia. Hippocampal volume was associated with frontal white matter NAA, whereas thalamic volume was associated with both frontal white matter NAA and basal ganglia Glx. Analyses of relative metabolite concentrations (referenced to Cr) yielded weaker effects, although more metabolites were retained as significant predictors in the models than the analysis of absolute concentrations. These findings demonstrate that reduced cortical and subcortical volumes, which have been previously found to be linked to HIV status and history, are also strongly associated with the degree of cerebral metabolite disturbance observed via MRS. Reduced cortical and hippocampal volumes were most strongly associated with decreased NAA, though reduced Glx also tended to be associated with reduced cortical and subcortical volumes (caudate and thalamus) as well, suggesting both neuronal and glial disturbances. Interestingly, metabolite-volumetric relationships were not limited to the cortical region from which MRS was measured, possibly reflecting shared pathophysiological processes. The relationships between Cho and volumetric measures suggest a complicated relationship possibly related to the effects of inflammatory processes on brain volume. The findings demonstrate the relationship between MRI-derived measures of cerebral metabolite disturbances and structural brain integrity, which has implication in understanding HIV-associated neuropathological mechanisms.     

急性脑梗死后血管性认知障碍的磁共振波谱研究

目的应用质子磁共振波谱(1 H-MRS)技术,探讨急性脑梗死后血管性认知障碍(VCI)患者的颅内物质代谢变化与认知损害的关系。方法对86例脑梗死患者(脑梗死组)及21名健康对照者(对照组)进行简易精神状态检查量表(MMSE)和蒙特利尔认知评分量表(MoCA)评分,并计算其视空间及执行功能评分。根据认知评分结果,将脑梗死组分为脑梗死后认知功能正常组(NCI)、脑梗死后VCI非痴呆组(VCIND)、脑梗死后痴呆组。对脑梗死组及健康对照进行1 H-MRS检查,测定右额叶、左颞叶、左丘脑及顶枕叶交界处N-乙酰天冬氨酸(NAA)/肌酸(Cr)、肌醇(mI)/Cr及胆碱复合物(Cho)/Cr比值,并分析脑梗死组物质代谢比值与认知评分(MoCA评分、视空间及执行功能)间的相关性。结果 (1)与对照组(左颞叶及左丘脑NAA/Cr 1.53±0.08、1.52±0.10)相比,VCIND组左颞叶及左丘脑NAA/Cr(1.46±0.07、1.47±0.07)降低(P=0.001、P=0.006);与VCIND组右额叶1.46±0.10比较,梗死后痴呆组右额叶、左颞叶及左丘脑NAA/Cr(1.38±0.14、1.39±0.06、1.42±0.09)降低(分别P<0.001、P<0.001、P=0.003)。对照组及NCI组间的各区域物质代谢比值无统计学差异(均P>0.05)。(2)所有脑梗死患者中,除右额叶Cho/Cr外,余各感兴趣区物质代谢比值与MoCA评分间均相关,其中以左颞叶、左丘脑NAA/Cr值与MoCA评分的相关性为著(分别r=0.566,P<0.001;r=0.485,P<0.001);除右额叶、丘脑及顶枕叶交界处Cho/Cr外,余各物质代谢比值与视空间及执行功能评分间相关,其中亦以左颞叶及左丘脑NAA/Cr值的相关性为著(分别NAA/Cr为r=0.591,P<0.001;r=0.491,P<0.001)。结论左丘脑及左颞叶代谢异常可能为VCI患者认知损害的早期关键环节之一,随着VCI病变进展可能整个皮质及皮质下环路区域都将出现代谢异常。