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.     

Effects of Alzheimer disease on fronto-parietal brain N-acetyl aspartate and myo-inositol using magnetic resonance spectroscopic imaging

Previous magnetic resonance (MR) spectroscopy studies of Alzheimer disease (AD) reporting reduced N-acetyl aspartate (NAA) and increased myo-Inositol (mI) used single voxel techniques, which have limited ability to assess the regional distribution of the metabolite abnormalities. The objective of this study was to determine the regional distribution of NAA and mI alterations in AD by using MR spectroscopic imaging. Fourteen patients with AD and 22 cognitively normal elderly were studied using structural MR imaging and MR spectroscopic imaging. Changes of NAA, mI, and various metabolite ratios were measured in frontal and parietal lobe gray matter (GM) and white matter. This study found: (1) when compared with cognitively normal subjects, AD patients had increased mI and mI/creatine (Cr) ratios primarily in parietal lobe GM, whereas frontal lobe GM and white matter were spared; (2) in the same region where mI was increased, AD patients had also decreased NAA and NAA/Cr ratios, replicating previous findings; (3) however, increased mI or mI/Cr ratios did not correlate with decreased NAA or NAA/Cr ratios; and (4) using mI/Cr and NAA/Cr together improved sensitivity and specificity to AD from control as compared with NAA/Cr alone. In conclusion, decreased NAA and increased mI in AD are primarily localized in parietal lobe GM regions. However, the NAA and mI changes are not correlated with each other, suggesting that they represent different processes that might help staging of AD.     

Proton magnetic resonance spectroscopy (1H-MRS) of the thalamus in schizophrenia.

This study applied (1)H-MRS in the thalamus of schizophrenic patients and healthy subjects. There were no differences in the metabolite ratios (NAA/Cr, Cho/Cr or mI/Cr) between the two groups. Relationships were noted between NAA/Cr and age in patients with a trend toward this correlation in controls, suggesting an effect of age on the metabolism of the thalamus.     

Proton magnetic resonance spectroscopy (H-MRS) of the thalamus in schizophrenia

This study applied ¹H-MRS in the thalamus of schizophrenic patients and healthy subjects.There were no differences in the metabolite ratios (NAA/Cr, Cho/Cr or mI/Cr) between the two groups. Relationships were noted between NAA/Cr and age in patients with a trend toward this correlation in controls, suggesting an effect of age on the metabolism of the thalamus.     

Thalamic abnormalities in patients with schizophrenia revealed by proton magnetic resonance spectroscopy

Recent investigations suggest that thalamic abnormalities may underlie symptom formation in schizophrenia. We previously demonstrated reduced concentrations of N-acetylaspartate (NAA) in tissue from the thalamus of schizophrenic patients using in vitro proton magnetic resonance spectroscopy (1H-MRS). In the present study, in vivo 1H-MR spectra of the left thalamus and frontal lobe were investigated in 20 patients with schizophrenia and 16 age-matched control subjects to replicate our previous postmortem findings and support the hypothesis of thalamic abnormality in schizophrenia. Schizophrenic patients showed significantly lower NAA/total creatine (Cr) and choline-containing compounds (Cho)/Cr ratios in the thalamus than control subjects, while no significant difference was found in the frontal lobe. There was no significant correlation in the schizophrenic patients between the NAA/Cr or Cho/Cr ratio and other clinical data including clinical symptoms or neuroleptic dosage. These findings may further support other studies suggesting decreased thalamic volume or neuronal number and/or thalamic dysfunction, and reduction in size of white matter tracts adjacent to the thalamus in schizophrenia, as well as our previous postmortem MRS study.     

Proton magnetic resonance spectroscopy of the frontal lobe and cerebellar vermis in children with a mood disorder and a familial risk for bipolar disorders

OBJECTIVE: Few studies have examined the neurochemical abnormalities that might be associated with pediatric bipolar disorder. The aim of this study was to use magnetic resonance spectroscopy to evaluate several brain regions implicated in bipolar disorder in children with a mood disorder and a familial risk for bipolar disorder. We hypothesized that these children would exhibit neurochemical differences compared with healthy children of parents without a psychiatric disorder. Specifically, decreased N-acetylaspartate (NAA) and creatine and phosphocreatine (Cr) of the prefrontal cortex and cerebellar vermis would reflect impairments in neuronal function and cellular metabolism, and elevated myo-inositol (mI) would reflect impaired phosphoinositide metabolism, potentially representing early markers of neurophysiologic changes that might underlie the development of bipolar disorder. METHODS: Children with a mood disorder and at least one parent with bipolar disorder (n = 9) and healthy children (n = 10) group matched for age (8-12 years), race, sex, education, and Tanner stage were evaluated using the Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia. Proton magnetic resonance spectroscopy was acquired using 8-cc volumes within the frontal cortex, frontal white matter, and the cerebellar vermis. Metabolite ratios (NAA/Cr, cholines (Cho)/Cr, mI/Cr, NAA/Cho, NAA/mI, and Cho/mI) and concentrations (NAA, Cr, Cho, and mI) were calculated and compared between groups. RESULTS: The trend in concentration levels of NAA and Cr was approximately 8% lower for children with a mood disorder than healthy children within the cerebellar vermis. The frontal cortex in children with a mood disorder revealed elevated mI concentration levels, approximately 16% increased, compared with healthy children. CONCLUSIONS: Similar to findings in adults with bipolar disorders, neurochemical abnormalities within the frontal cortex and the cerebellar vermis were present in this preliminary comparison of children with a mood disorder and a familial risk for bipolar disorder. Larger sample sizes are needed to replicate these findings.     

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.     

双相抑郁患者前额叶及海马磁共振质子波谱成像研究

目的探讨双相抑郁患者前额叶及海马磁共振质子波谱(proton magnetic resonance spectroscopy,1H-MRS)的代谢物变化特点,为其神经生物学研究提供线索。方法应用磁共振质子波谱成像技术检测26例双相抑郁患者(患者组)和26例单相抑郁患者及13例健康志愿者(对照组)双侧前额叶白质、前扣带回皮质、海马N-乙酰天门冬氨酸(N-Acetylaspartate,NAA)、胆碱(choline,Cho)、肌酸(creatine,Cr)3种代谢物,以Cr为参照物,分别计算双侧NAA/Cr和Cho/Cr比值。采用SPSS 13.0进行统计处理。结果患者组左侧前额叶白质NAA/Cr(1.65±0.31)低于对照组(2.37±0.36),左侧前额叶白质Cho/Cr(1.35±0.27)低于对照组(1.65±0.21),差异有统计学意义(P<0.05);右侧前额叶白质NAA/Cr、Cho/Cr值与正常对照组差异无统计学意义;患者组双侧前扣带回NAA/Cr、Cho/Cr值与正常对照组差异无统计学意义;患者组双侧海马NAA/Cr、Cho/Cr值与正常对照组差异无统计学意义;患者组与单相抑郁组的双侧额叶白质、双侧前扣带回皮质、双侧海马NAA/Cr、Cho/Cr值差异均无统计学意义。结论双相抑郁患者可能存在左侧前额叶神经元功能下降和膜磷脂代谢异常,其代谢物特点存在偏侧化。     

Focal and lateralized subcortical abnormalities in unipolar major depressive disorder: an automated multivoxel proton magnetic resonance spectroscopy study.

BACKGROUND: The results of prior proton magnetic resonance spectroscopy ((1)H-MRS) studies in unipolar major depressive disorder (MDD) evaluating choline (Cho)/creatine (Cr) and N-acetyl-L-aspartate (NAA)/Cr ratios are mixed. These single-voxel or one-dimensional chemical-shift imaging (CSI) nonautomated (1)H-MRS studies has been unable to evaluate global or lateralized abnormalities in neuronal or membrane function. Using automated multivoxel two-dimensional CSI (1)H-MRS techniques, we tested the hypothesis that patients with MDD have focal neuronal and membrane abnormalities localized in the subcortical region. METHODS: Whole brain and subcortical measures of Cho, NAA, Cr, and myo-inositol (mI) were obtained in 18 patients with MDD and 20 control subjects using automated two-dimensional CSI (1)H-MRS. RESULTS: Compared with control subjects, MDD patients had a significantly lower mean NAA/Cr amplitude in the caudate and a significantly higher mean Cho/Cr amplitude in the putamen, particularly on the right side. No differences were observed for global whole brain measurements. CONCLUSIONS: The findings support reduced neuronal viability or function in the caudate and altered membrane phospholipid metabolism in the putamen for patients with MDD. Our results are consistent with prior magnetic resonance imaging, positron emission tomography, and postmortem reports of focal and lateralized abnormalities of the basal ganglia in MDD.     

Metabolic changes in 37 newly diagnosed Wilson's disease patients assessed by magnetic resonance spectroscopy

Wilson's Disease (WD) is a rare autosomal recessive disorder. The literature about proton MR spectroscopy (MRS) in WD is based mostly on data derived from patients undergoing treatment. The aim of this study was to identify brain metabolic changes in newly diagnosed WD patients using MRS to elucidate the pathomechanism of the cerebral pathology of WD. The globus pallidus and thalamus of 37 patients with WD were examined bilaterally with MRS. The calculations were performed for: myoinositol (mI), choline (Cho), creatine (Cr), N-acetyl-aspartate (NAA), lipid (Lip), glutamine, and glutamate (Glx). In all WD patients a significantly decreased mI/Cr and NAA/Cr ratio levels and an increased Lip/Cr ratio in the pallidum were observed. Analysis revealed a significantly increased Glx/Cr and Lip/Cr ratio in the thalamus. In the pallidum of neurologically impaired patients, Cho/Cr, Glx/Cr and Lip/Cr ratios were higher than in control subjects, and the NAA/Cr was significantly lower. In hepatic patients, the mI/Cr, Cho/Cr and NAA/Cr ratio levels were lower than in controls. The Cho/Cr and Lip/Cr ratios were higher in the thalami of neurologically impaired patients, and Lip/Cr ratios were higher than controls' in hepatic patients. Both findings were statistically significant. Compared to the thalamus, the basal ganglia are more sensitive to ongoing degenerative changes and portal-systemic encephalopathy in WD. The NAA/Cr reduction in hepatic and neurologically impaired patients could indicate that neurodegeneration is associated with all presentations of WD. In hepatic patients a mI and Cho decrease and in neurological Glx increase can be caused by porto-systemic shunting.     

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.     

Gray and white matter brain chemistry in young children with autism

CONTEXT: The brain pathophysiological abnormalities underlying autism remain unclear. Neuroimaging and histological studies suggest cellular abnormalities early in the course of the disease. OBJECTIVE: To measure the in vivo chemical profile of gray and white matter tissues in autism. DESIGN: Cross-sectional spectroscopic imaging study comparing 3- to 4-year-old children with autism spectrum disorder (ASD) with age-matched comparison groups of children with delayed development (DD) and typical development (TD). SETTING: The University of Washington Diagnostic Imaging Sciences Center, Seattle. PARTICIPANTS: Forty-five 3- to 4-year-old children with ASD, 12 age-matched children with DD, and 10 age-matched children with TD. MAIN OUTCOME MEASURES: Estimates of gray and white matter concentrations for choline-containing compounds (Cho), creatine plus phosphocreatine, N-acetylaspartate (NAA), and myo-inositol (mI). Transverse relaxation times for Cho, creatine plus phosphocreatine, and NAA expressed relative to control subjects with TD were examined to evaluate tissue compactness. RESULTS: The children with ASD demonstrated decreased gray matter concentrations of Cho (P < .001), creatine plus phosphocreatine (P = .02), NAA (P = .02), and mI (P = .008) compared with children with TD. Gray matter Cho transverse relaxation was also prolonged for the ASD sample compared with the TD group (P = .01). The children with ASD demonstrated significantly decreased levels of Cho (P = .04) and mI (P = .008) and trend-level NAA (P = .09) in gray matter compared with the DD group. For white matter, both children with ASD and children with DD showed a similar pattern of NAA and mI level decreases (for children with ASD vs children with TD: NAA, P = .03; mI, P = .04; for children with DD vs children with TD, NAA, P = .03; mI, P = .07). In several analyses, cerebral volume contributed significantly as a covariate. CONCLUSIONS: Reduced gray matter chemical concentrations and altered Cho transverse relaxation, in a pattern distinct from that in children with DD, suggest decreased cellularity, or density, at this early time point in ASD. Possibly reflecting shared developmental features, white matter results were common to ASD and DD groups. The relationship between cerebral volume and neurochemistry at this early time point may indicate processes related to unit scaling.     

N-acetylaspartate reductions in the mediodorsal and anterior thalamus in men with schizophrenia verified by tissue volume corrected proton MRSI

OBJECTIVE: Deficits in the mediodorsal and anterior nuclei of the thalamus may contribute to the psychopathological symptoms of schizophrenia. These thalamic nuclei have been found to be abnormal in schizophrenia and have close connections with other brain structures implicated in the disorder. We therefore examined schizophrenia-related alterations in brain metabolite levels specifically in the mediodorsal and anterior thalamic subregions. METHOD: We used in vivo proton magnetic resonance spectroscopic imaging ((1)H MRSI) to measure N-acetylaspartate (NAA), choline-containing compounds (Cho), and creatine+phosphocreatine (Cr) in the mediodorsal and anterior thalamus in 22 male patients with schizophrenia and 22 male controls. Magnetic resonance imaging (MRI) tissue segmentation and thalamic volume mask techniques were performed to distinguish the thalamus, extrathalamic gray and white matter, and CSF within the spectroscopic voxels. RESULTS: Compared to healthy subjects, patients with schizophrenia had significantly lower NAA in the mediodorsal and anterior thalamus bilaterally. No significant differences in Cho or Cr levels were seen. NAA was significantly higher in the left thalamus relative to the right in both groups. We found a strong negative correlation between left thalamic NAA and duration of illness, even after partialling out the effect of age. Tissue segmentation and thalamic volume mask techniques detected no group or lateralized differences in tissue type or CSF percentages, demonstrating that the metabolite reductions were not an artifact of spectroscopic voxel heterogeneity. CONCLUSIONS: These findings suggest diminished function and/or structure in the mediodorsal and anterior thalamus in male patients with schizophrenia and support earlier research demonstrating schizophrenia-related abnormalities in the thalamus and its circuitry.     

Single voxel proton magnetic resonance spectroscopy in women with and without intimate partner violence-related posttraumatic stress disorder

Preliminary in vivo proton magnetic spectroscopic ((1)H-MRS) studies of N-acetylaspartate (a putative marker of neuronal viability and function) in combat veterans and maltreated children with posttraumatic stress disorder (PTSD) suggest altered neuronal integrity in anterior cingulate and medial temporal lobe structures. In this study, (1)H-MRS was used to measure N-acetylaspartate (NAA), choline (Cho) and myo-inositol (mI) relative to creatine (Cr) in the anterior cingulate of 16 women with histories of intimate partner violence (7 with a DSM-IV diagnosis of PTSD, 9 without PTSD) and 11 healthy, non-abused comparison subjects. The relationship between anterior cingulate chemistry and performance on the Stroop Color-Word task and Part B of the Trail Making Test was also examined. There were no significant differences in anterior cingulate or occipital gray matter metabolite ratios of NAA/Cr and Cho/Cr between intimate partner violence and healthy comparison subjects. Intimate partner violence subjects with PTSD had significantly higher anterior cingulate Cho/Cr than intimate partner violence subjects without PTSD. There was evidence that the subjects with PTSD suffered more severe intimate partner violence as measured by the Conflict Tactics Scale-Revised. Metabolite ratios were not significantly correlated with performance on the Stroop or Trails B. Our findings, in agreement with earlier studies, showed significant alterations in anterior cingulate chemistry in women with PTSD. In contrast to other studies, we found an increase in Cho/Cr rather than a decrease in NAA/Cr, indicating alterations in glia, instead of neuronal dropout.     

Proton MRS in twin pairs discordant for schizophrenia

Proton magnetic resonance spectroscopy ((1)H MRS) neurometabolite abnormalities have been detected widely in subjects with and at risk for schizophrenia. We hypothesized that such abnormalities would be present both in patients with schizophrenia and in their unaffected twin siblings. We acquired magnetic resonance spectra (TR/TE=3000/30 ms) at voxels in the mesial prefrontal gray matter, left prefrontal white matter and left hippocampus in 14 twin pairs discordant for schizophrenia (2 monozygotic, 12 dizygotic), 13 healthy twin pairs (4 monozygotic, 9 dizygotic) and 1 additional unaffected co-twin of a schizophrenia proband. In the mesial prefrontal gray matter voxel, N-acetylaspartate (NAA), creatine+phosphocreatine (Cr), glycerophosphocholine+phosphocholine (Cho) and myo-inositol (mI) did not differ significantly between patients with schizophrenia, their unaffected co-twins or healthy controls. However, glutamate (Glu) was significantly lower in patients with schizophrenia (31%, percent difference) and unaffected co-twins (21%) than in healthy controls (collapsed across twin pairs). In the left hippocampus voxel, levels of NAA (23%), Cr (22%) and Cho (36%) were higher in schizophrenia patients compared with controls. Hippocampal NAA (25%), Cr (22%) and Cho (37%) were also significantly higher in patients than in their unaffected co-twins. Region-to-region differences in metabolite levels were also notable within all three diagnosis groups. These findings suggest that (1)H MRS neurometabolite abnormalities are present not only in patients with schizophrenia, but also in their unaffected co-twins. Thus, reduced mesial prefrontal cortical Glu and elevated hippocampal NAA, Cr and Cho may represent trait markers of schizophrenia risk and, when exacerbated, state markers of schizophrenia itself.     

精神分裂症患者前额叶和丘脑的质子磁共振波谱研究

Objective To identify the metabolite levels in prefrontal lobe and thalamus in patients with schizophrenia by proton magnetic resonance spectroscopy (1H-MRS). Methods Thirty-eighty schizophrenics and 38 normal controls were involved in this study. A multi-voxel 1H-MRS was given to all the subjects on prefrontal lobe and thalamus within 24 hours they got in hospital. The N-acetylaspartate (NAA), choline-congtaining compounds (Cho), and creatine compounds (Cr) were measured and the ratios of NAA/Cr, Cho/Cr and NAA/( Cho + Cr) were determined Results In left prefrontal lobe and bilateral thalamus, the NAA/Cr ratio in patients demonstrated lower than that in normal controls ( all P <0. 05). In left prefrontal lobe, the NAA/(Cho + Cr) ratio in patients showed lower than that in normal controls (0. 64 ±0. 13 vs. 0. 74±0. 22,t =2. 26, P<0. 05). Both in patients and in normal controls, there were no significant differences in NAA/Cr, Cho/Cr and NAA/(Cho + Cr) between the two sides (all P >0. 05). Conclusious Abnormalities in neuronal function and/or integrity are present in schizophrenics.There is no significantly lateralized asymmetry for metabolite levels such as NAA, Cho and Cr in either the schizophrenics or the controls.     

Neurochemical pathology in hippocampus in euthymic patients with bipolar I disorder

Objective: Subcortical regions such as hippocampus, thalamus and ventral putamen are assumed to be involved in the pathophysiology of mood regulation. Disturbed hippocampal neuronal function indicated by reduced N‐acetyl‐aspartate (NAA) levels in bipolar patients was shown by several studies. Results in thalamus and putamen are inconsistent. Method: N‐acetyl‐aspartate, choline (Cho), creatine (Cr) and myo‐inositol (Ins) were measured in left hippocampus, left thalamus and left putamen using proton magnetic resonance spectroscopy in 13 euthymic patients with bipolar I disorder and 13 pairwise matched healthy control subjects. Metabolic ratios NAA/Cr, NAA/Cho, Cho/Cr and Ins/Cr were calculated. Results: Patients with bipolar I disorder demonstrated significantly reduced NAA/Cr in the left hippocampus compared with healthy control subjects. No alterations were found in thalamus or putamen. Conclusion: We hypothesize that this NAA/Cr reduction might reflect neuronal dysfunction in the left hippocampus in patients with bipolar disorder.     

Subtype-associated metabolite differences in the temporal lobe in schizophrenia detected by proton magnetic resonance spectroscopy

Brain imaging studies have indicated that the medial temporal lobe functions aberrantly in schizophrenic patients. Both diagnostic subtype and gender may affect functional and morphologic abnormalities in this region. We investigated subtype- and gender-associated differences in metabolites in the left medial temporal lobe in 40 medicated schizophrenic patients by proton magnetic resonance spectroscopy and compared findings with those in 40 healthy control subjects. Peaks corresponding to N-acetylaspartate (NAA), choline-containing compounds (Cho), creatine-phosphocreatine (Cr), and inositol were measured. Schizophrenic patients showed a decrease in the NAA/Cr ratio in the left medial temporal lobe, and patients with the disorganized subtype of illness showed significantly lower NAA/Cr and Cho/Cr ratios than those with paranoid schizophrenia. The NAA/Cr ratio in patients with the undifferentiated subtype also was significantly lower than in the paranoid subtype. No significant associations were observed between metabolite ratios and clinical symptom scores, age at onset of illness, or gender. These findings suggest that patients with the disorganized and undifferentiated subtypes have greater impairments in neuronal integrity or function in the left medial temporal lobe than patients with other subtypes of schizophrenia.     

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.     

Proton magnetic resonance spectroscopy in dementia with Lewy bodies

Proton magnetic resonance spectroscopy ((1)H-MRS) provides a non-invasive, in vivo insight into the brain metabolism, and has been successfully used in several neurological conditions. Our objective was to characterise the cerebral metabolic changes in dementia with Lewy bodies (DLB) patients using (1)H-MRS. Single Voxel (1)H-MRS was performed in 12 DLB patients with mild to moderate symptoms and 11 age-matched healthy controls. Volumes of interest (VOI) were selected, including white matter (WM) in the centrum semiovale and grey matter (GM) in the parasagittal parietal cortex. Main metabolic peaks corresponding to N-acetylaspartate (NAA), glutamate/glutamine (Glx), choline-containing compounds (Cho), myo-inositol (Ins), and creatine plus phosphocreatine (Cr) were identified. These areas were measured and referred to that of the water. Metabolic ratios among the different peak areas were also calculated. In comparison with the control group, DLB patients showed significantly lower mean NAA/Cr, Glx1/Cr and Cho/Cr ratios in the WM, while their Ins/Cr and Ins/NAA ratios did not differ from those of the control group. In the GM, no significant differences were found between both groups. Correlations between age at onset, disease duration, Mini-Mental State Examination, the motor section of the Unified Parkinson's Disease Rating Scale, Hoehn and Yahr staging and metabolic ratios, both for WM and GM, were not significant in DLB patients. Our spectroscopy data show WM involvement, along with GM preservation, in DLB patients with early or intermediate stages. Hence, (1)H-MRS may provide adjunctive information in the ante-mortem diagnosis of DLB.