Brain choline concentration. Early quantitative marker of ischemia and infarct expansion?

OBJECTIVE: Better prediction of tissue prognosis in acute stroke might improve treatment decisions. We hypothesized that there are metabolic ischemic disturbances measurable noninvasively by proton magnetic resonance spectroscopy ((1)H MRS) that occur earlier than any structural changes visible on diffusion-tensor imaging (DTI), which may therefore serve for territorial identification of tissue at risk. METHODS: We performed multivoxel (1)H MRS plus DTI within a maximum of 26 hours, and DTI at 3-7 days, after ischemic stroke. We compared choline, lactate, N-acetylaspartate, and creatine concentrations in normal-appearing voxels that became infarcted (infarct expansion) with normal-appearing voxels around the infarct that remained "healthy" (nonexpansion) on follow-up DTI. Each infarct expansion voxel was additionally classified as either complete infarct expansion (infarcted tissue on follow-up DTI covered > or =50% of the voxel) or partial infarct expansion (<50% of voxel). RESULTS: In 31 patients (NIH Stroke Scale score 0-28), there were 108 infarct nonexpansion voxels and 113 infarct expansion voxels (of which 80 were complete expansion and 33 partial expansion voxels). Brain choline concentration increased for each change in expansion category from nonexpansion, via partial expansion to complete expansion (2,423, 3,843, 4,158 IU; p < 0.05). Changes in lactate, N-acetylaspartate, and creatine concentrations in expansion category were insignificant although for lactate there was a tendency to such association. CONCLUSIONS: Choline concentration measurable with (1)H MRS was elevated in peri-ischemic normal-appearing brain that became infarcted by 3-7 days. The degree of elevation was associated with the amount of infarct expansion. (1)H MRS might identify DTI-normal-appearing tissue at risk of conversion to infarction in early stroke.

A diffusion tensor MRI study of white matter integrity in subjects at high genetic risk of schizophrenia.

Diffusion tensor imaging (DTI) has previously shown compromised white matter integrity in frontotemporal white matter fibers in patients with schizophrenia, as indicated by reduced fractional anisotropy (FA). In the present study we investigated whether reduced white matter FA is also present in relatives of individuals with schizophrenia who are at high risk (HR) for genetic reasons. Twenty-two HR subjects, 31 patients with schizophrenia and 51 control subjects underwent DTI. We compared FA between the three groups in the cingulum cingulate gyri, the uncinate and the arcuate fasciculi and the anterior limb of the internal capsules (ALIC). A voxel-based analysis showed lower FA in patients with schizophrenia compared to controls in left and right uncinate (p<0.03), the left arcuate (p<0.03) and left and right ALIC (p<0.01). Using an automatic region-of-interest analysis, less sensitive to potential misregistration errors, produced essentially the same results, as well as reduced FA of the ALIC in the HR group compared to controls (p<0.05). This study replicates previous findings showing lower FA in frontotemporal white matter fibers of schizophrenia patients. We also found reduced FA in the ALIC of both patients and subjects at high risk of schizophrenia when compared to controls. This may be a possible indicator of the higher vulnerability of relatives to develop the disorder.

The effects of a neuregulin 1 variant on white matter density and integrity.

Theories of abnormal anatomical and functional connectivity in schizophrenia and bipolar disorder are supported by evidence from functional magnetic resonance imaging (MRI), structural MRI and diffusion tensor imaging (DTI). The presence of similar abnormalities in unaffected relatives suggests such disconnectivity is genetically mediated, albeit through unspecified loci. Neuregulin 1 (NRG1) is a psychosis susceptibility gene with effects on neuronal migration, axon guidance and myelination that could potentially explain these findings. In the current study, unaffected subjects were genotyped at the NRG1 single nucleotide polymorphism (SNP) rs6994992 (SNP8NRG243177) locus, previously associated with increased risk for psychosis, and the effect of genetic variation at this locus on white matter density (T(1)-weighted MRI) and integrity (DTI) was ascertained. Subjects with the risk-associated TT genotype had reduced white matter density in the anterior limb of the internal capsule and evidence of reduced structural connectivity in the same region using DTI. We therefore provide the first imaging evidence that genetic variation in NRG1 is associated with reduced white matter density and integrity in human subjects. This finding is discussed in the context of NRG1 effects on neuronal migration, axon guidance and myelination.