3T diffusion-weighted MRI of the thyroid gland with reduced distortion: preliminary results.

OBJECTIVE: Single-shot diffusion-weighted (DW) echo planar imaging (EPI), which is commonly used for imaging the thyroid, is characterised by severe blurring and distortion. The objectives of this work were: 1, to show that a reduced-field of view (r-FOV) DW EPI technique can improve image quality; and 2, to investigate the effect of different reconstruction strategies on the resulting apparent diffusion coefficients (ADCs). METHODS: We implemented a single-shot, r-FOV DW EPI technique with a two-dimensional radiofrequency excitation pulse for DW imaging of the thyroid at 3T. Images were reconstructed using root sum of squares (SOS) and an optimal-B1 reconstruction (OBR). Phantom and in vivo experiments were performed to compare r-FOV and conventional full-FOV DW EPI with root SOS and OBR. RESULTS: r-FOV with OBR substantially improved image quality at 3T. In phantoms, r-FOV gave more accurate ADCs than full-FOV. In vivo r-FOV always gave lower ADC values with respect to the full-FOV technique irrespective of the reconstruction used and whether only two or multiple b-values were used to compute the ADCs. CONCLUSION: r-FOV DW EPI can reduce image blurring and distortion at the expense of a low signal-to-noise ratio. OBR is a promising reconstruction technique for accurate ADC measurements in lower signal-to-noise ratio regimes, although further studies are needed to characterise its performance. ADVANCES IN KNOWLEDGE: DW imaging of the thyroid at 3T could potentially benefit from r-FOV acquisition strategies, such as the r-FOV DW EPI technique proposed in this paper.

DCE and DW MRI in monitoring response to androgen deprivation therapy in patients with prostate cancer: a feasibility study.

Androgen deprivation therapy (ADT) is a key primary treatment for advanced and metastatic prostate cancer and is an important neoadjuvant before radiotherapy. We evaluated 3.0 T dynamic contrast-enhanced MRI and diffusion-weighted (DW) MRI in monitoring ADT response. Twenty-three consecutive patients with prostate cancer treated by primary ADT were included. Imaging was performed at baseline and 3 months posttreatment with ADT. After 3 months therapy there was a significant reduction in all dynamic contrast-enhanced MRI parameters measured in tumor regions of interest (K(trans), k(ep), v(p), IAUGC-90); P < 0.001. Areas of normal-appearing peripheral zone showed no significant change; P = 0.285-0.879. Post-ADT, there was no significant change in apparent diffusion coefficient values in tumors, whilst apparent diffusion coefficient values significantly decreased in areas of normal-appearing peripheral zone, from 1.786 × 10(-3) mm(2) /s to 1.561 × 10(-3) mm(2) /s; P = 0.007. As expected the median Prostate-Specific Antigen (PSA) significantly reduced from 30 ng/mL to 1.5 ng/mL posttreatment, and median prostate volume dropped from 47.6 cm(3) to 24.9 cm(3) ; P < 0.001. These results suggest that dynamic contrast-enhanced MRI and diffusion-weighted MRI offer different information but that both could prove useful adjuncts to the anatomical information provided by T2-weighted imaging. dynamic contrast-enhanced as a marker of angiogenesis may help demonstrate ADT resistance and diffusion-weighted imaging may be more accurate in determining presence of tumor cell death versus residual tumor.

Thalamic glutamate levels as a predictor of cortical response during executive functioning in subjects at high risk for psychosis.

CONTEXT: Alterations in glutamatergic neurotransmission and cerebral cortical dysfunction are thought to be central to the pathophysiology of psychosis, but the relationship between these 2 factors is unclear. OBJECTIVE: To investigate the relationship between brain glutamate levels and cortical response during executive functioning in people at high risk for psychosis (ie, with an at-risk mental state [ARMS]). DESIGN: Subjects were studied using functional magnetic resonance imaging while they performed a verbal fluency task, and proton magnetic resonance spectroscopy was used to measure their brain regional glutamate levels. SETTING: Maudsley Hospital, London, England. PATIENTS AND OTHER PARTICIPANTS: A total of 41 subjects: 24 subjects with an ARMS and 17 healthy volunteers (controls). MAIN OUTCOME MEASURES: Regional brain activation (blood oxygen level-dependent response); levels of glutamate in the anterior cingulate, left thalamus, and left hippocampus; and psychopathology ratings at the time of scanning. RESULTS: During the verbal fluency task, subjects with an ARMS showed greater activation than did controls in the middle frontal gyrus bilaterally. Thalamic glutamate levels were lower in the ARMS group than in control group. Within the ARMS group, thalamic glutamate levels were negatively associated with activation in the right dorsolateral prefrontal and left orbitofrontal cortex, but positively associated with activation in the right hippocampus and in the temporal cortex bilaterally. There was also a significant group difference in the relationship between cortical activation and thalamic glutamate levels, with the control group showing correlations in the opposite direction to those in the ARMS group in the prefrontal cortex and in the right hippocampus and superior temporal gyrus. CONCLUSIONS: Altered prefrontal, hippocampal, and temporal function in people with an ARMS is related to a reduction in thalamic glutamate levels, and this relationship is different from that in healthy controls.

Spinal cord repair in MS: does mitochondrial metabolism play a role?

OBJECTIVE: To investigate the mechanisms of spinal cord repair and their relative contribution to clinical recovery in patients with multiple sclerosis (MS) after a cervical cord relapse, using spinal cord (1)H-magnetic resonance spectroscopy (MRS) and volumetric imaging. METHODS: Fourteen patients with MS and 13 controls underwent spinal cord imaging at baseline and at 1, 3, and 6 months. N-acetyl-aspartate (NAA) concentration, which reflects axonal count and metabolism in mitochondria, and the cord cross-sectional area, which indicates axonal count, were measured in the affected cervical region. Mixed effect linear regression models investigated the temporal evolution of these measures and their association with clinical changes. Ordinal logistic regressions identified predictors of recovery. RESULTS: Patients who recovered showed a sustained increase in NAA after 1 month. In the whole patient group, a greater increase of NAA after 1 month was associated with greater recovery. Patients showed a significant decline in cord area during follow-up, which did not correlate with clinical changes. A worse recovery was predicted by a longer disease duration at study entry. CONCLUSIONS: The partial recovery of N-acetyl-aspartate levels after the acute event, which is concurrent with a decline in cord cross-sectional area, may be driven by increased axonal mitochondrial metabolism. This possible repair mechanism is associated with clinical recovery, and is less efficient in patients with longer disease duration. These insights into the mechanisms of spinal cord repair highlight the need to extend spinal cord magnetic resonance spectroscopy to other spinal cord disorders, and explore therapies that enhance recovery by modulating mitochondrial activity.

Spinal cord spectroscopy and diffusion-based tractography to assess acute disability in multiple sclerosis.

There is a need to assess spinal cord involvement in multiple sclerosis with new imaging techniques in order to understand better the underlying pathology. We aimed to evaluate whether quantitative MRI measures, obtained using single-voxel (1)H-MR spectroscopy of the cervical cord and diffusion-based tractography of the major spinal cord pathways, in patients with a cervical cord relapse, differed from controls and correlated with acute disability. Fourteen patients at the onset of a cervical cord relapse with at least one lesion between C1 and C3 were imaged on a 1.5 T scanner and clinically assessed on the Expanded Disability Status Scale (EDSS), 9-hole peg test (HPT) and timed 25-foot walk test. Thirteen age- and gender-matched control subjects were also scanned. Metabolite concentrations, including total N-acetyl-aspartate (tNAA), choline-containing compounds (Cho), creatine plus phosphocreatine (Cr) and myo-Inositol (m-Ins), were quantified at C1-C3. Probabilistic tractography was performed at C1-C3 to track the lateral cortico-spinal tracts in the lateral columns, the anterior cortico-spinal tracts and the anterior spino-thalamic fasciculi in the anterior columns, and the bilateral fasciculus gracilis and cuneatus in the posterior columns. Diffusion- and tractography-derived measures of these tracts, including fractional anisotropy and voxel-based connectivity, which reflect fibre integrity, were obtained. These MRI measures were compared between patients and controls using the Mann-Whitney test. Univariate correlations between MRI measures and disability were assessed using the Spearman's rho correlation coefficient. Multiple regression analyses were performed to investigate which MRI measures independently correlated with the clinical scores, adjusting also for cross-sectional cord area, age and gender. Patients showed lower tNAA of the cervical cord, lower connectivity and lower fractional anisotropy of the lateral cortico-spinal tracts and posterior tracts, than controls. In patients, there were significant correlations between: (i) EDSS and m-Ins, Cho, Cr and radial diffusivity of the lateral cortico-spinal tracts; (ii) HPT and Cr, radial diffusivity of the lateral cortico-spinal tracts, connectivity and fractional anisotropy of the posterior tracts, and connectivity of the anterior tracts. M-Ins was independently associated with the EDSS, while Cr, tNAA and connectivity of the posterior tracts were independently associated with the HPT. MR spectroscopy and diffusion-based tractography of the cervical cord provide measures that are sensitive to the tissue damage occurring in this area in patients with a cervical cord relapse. These measures were found to correlate with acute disability. Our findings suggest that it would be worthwhile performing longitudinal studies and extending these novel techniques to other neurological diseases affecting the spinal cord.

1H-MRS internal thermometry in test-objects (phantoms) to within 0.1 K for quality assurance in long-term quantitative MR studies.

Many magnetic resonance test-object properties are temperature-dependent, with typical temperature coefficients of approximately 2-3% K(-1). Therefore, to achieve consistent quality assurance measurements to within 1%, test object temperatures should ideally be known to within 0.3 K. Proton magnetic resonance spectroscopy has previously been used to estimate accurately absolute tissue temperature in vivo, based on the linear temperature dependence of the chemical shift difference between water and temperature-stable reference metabolites such as N-acetylaspartate. In this study, this method of 'internal thermometry' in quality assurance test-objects was investigated, and in particular the value of sodium 3-(trimethylsilyl)propane-1-sulfonate (DSS) as a chemical shift reference was demonstrated. The relationship between the DSS-water chemical shift difference (sigma, expressed in ppm) and temperature tau (in K) was shown to be tau = 764.55 (+/-5.05) - 97.72 (+/-1.05) sigma (286

Metabolite changes in early relapsing-remitting multiple sclerosis. A two year follow-up study.

Previous in vivo proton magnetic resonance spectroscopic imaging ((1)H-MRSI) studies have found reduced levels of N-acetyl-aspartate (NAA) in multiple sclerosis (MS) lesions, the surrounding normal-appearing white matter (NAWM) and cortical grey matter (CGM), suggesting neuronal and axonal dysfunction and loss. Other metabolites, such as myoinositol (Ins), creatine (Cr), choline (Cho), and glutamate plus glutamine (Glx), can also be quantified by (1)H-MRSI, and studies have indicated that concentrations of these metabolites may also be altered in MS. Relatively little is known about the time course of such metabolite changes. This preliminary study aimed to characterise changes in total NAA (tNAA, the sum of NAA and N-acetyl-aspartyl-glutamate), Cr, Cho, Ins and Glx concentrations in NAWM and in CGM, and their relationship with clinical outcome, in subjects with clinically early relapsing-remitting MS (RRMS). Twenty RRMS subjects and 10 healthy control subjects underwent (1)H-MRSI examinations yearly for two years. Using the LCModel, tNAA, Cr, Cho, Ins and Glx concentrations were estimated both in NAWM and CGM. At baseline, the concentration of tNAA was significantly reduced in the NAWM of the MS patients compared to the control group (-7%, p = 0.003), as well as in the CGM (-8.7%, p = 0.009). NAWM tNAA concentrations tended to recover from baseline, but otherwise tissue metabolite profiles did not significantly change in the MS subjects, or relatively between MS and healthy control subjects. While neuronal and axonal damage is apparent from the early clinical stages of MS, this study suggests that initially it may be partly reversible. Compared with other MR imaging measures, serial (1)H-MRSI may be relatively less sensitive to progressive pathological tissue changes in early RRMS.

Metabolite changes in normal-appearing gray and white matter are linked with disability in early primary progressive multiple sclerosis.

BACKGROUND: Abnormalities in normal-appearing brain tissues may contribute to disability in primary progressive multiple sclerosis (PPMS), where few lesions are seen on conventional imaging. OBJECTIVES: To evaluate the mechanisms underlying disease progression in the early phase of PPMS by measuring metabolite concentrations in normal-appearing white matter (NAWM) and cortical gray matter (CGM) and to assess their relationship with clinical outcomes. DESIGN: Case-control study. SETTING: Tertiary referral hospital. Patients Forty-three consecutive patients within 5 years of onset of PPMS and 44 healthy control subjects. MAIN OUTCOME MEASURES: Concentrations of choline-containing compounds, phosphocreatine, myo-inositol, total N-acetyl-aspartate (tNAA), and glutamate-glutamine were estimated using proton magnetic resonance spectroscopic imaging. Brain parenchymal, white matter and gray matter fractions and proton density and gadolinium-enhancing lesion loads were calculated. The Expanded Disability Status Scale and Multiple Sclerosis Functional Composite scores were recorded. RESULTS: In CGM, concentrations of the tNAA (P<.001) and glutamate-glutamine (P = .005) were lower in patients with PPMS than in controls. In NAWM, myo-inositol levels were higher (P = .002) and tNAA levels were lower (P = .005) in patients with PPMS than in controls. The Expanded Disability Status Scale score correlated with the tNAA concentration in CGM (r = -0.44; P = .03) and with myo-inositol (r = 0.41; P = .01) and glutamate-glutamine concentrations (r = 0.41; P = .01) in NAWM. Proton density lesion load correlated negatively with CGM tNAA concentration and positively with NAWM myo-inositol concentration. CONCLUSION: Metabolite changes, which differ in CGM and NAWM, occur in early PPMS and are linked with disability.

Elevated white matter myo-inositol in clinically isolated syndromes suggestive of multiple sclerosis.

Normal-appearing white matter (NAWM) in established multiple sclerosis has been shown to be abnormal using a variety of magnetic resonance (MR) techniques, including proton MR spectroscopy ((1)H-MRS), although the stage at which these changes first appear is less clear. Using a 1.5 T scanner and single-voxel (1)H-MRS [TR 3000 ms, TE 30 ms, point-resolved spectroscopy (PRESS) localization], we determined NAWM metabolite concentrations in 96 patients a mean of 19 weeks (range 12-28 weeks) after onset of a clinically isolated syndrome (CIS) suggestive of multiple sclerosis and in 44 healthy control subjects. Absolute concentrations of N-acetyl-aspartate, total creatine and phosphocreatine (Cr), choline-containing compounds, glutamate plus glutamine, and myo-inositol (Ins) were estimated automatically using the LCModel. Compared with control subjects, the concentration of Ins was elevated in CIS NAWM (mean 3.31 mM, SD 0.86 versus mean 3.82 mM, SD 1.06; P = 0.001). The increase in Ins was also seen in the patient subgroup with abnormal T2-weighted MRI (mean 3.88 mM, SD 1.10; P = 0.001) and in those who satisfied the McDonald criteria for multiple sclerosis (mean 4.04 mM, SD 1.31; P = 0.001). An increase in Cr was also observed in CIS NAWM (P = 0.023), but other metabolites did not significantly differ between the whole CIS group and control subjects. There was no significant correlation between NAWM Ins and T2 lesion load. The early increase in Ins may reflect a process of pathogenic importance in multiple sclerosis NAWM. Follow-up studies will investigate whether the increase in NAWM Ins is of prognostic importance for future relapses and disability.

Metabolic profiles of human brain tumors using quantitative in vivo 1H magnetic resonance spectroscopy.

Proton spectroscopy can noninvasively provide useful information on brain tumor type and grade. Short- (30 ms) and long- (136 ms) echo time (TE) (1)H spectra were acquired from normal white matter (NWM), meningiomas, grade II astrocytomas, anaplastic astrocytomas, glioblastomas, and metastases. Very low myo-Inositol ([mI]) and creatine ([Cr]) were characteristic of meningiomas, and high [mI] characteristic of grade II astrocytomas. Tumor choline ([Cho]) was greater than NWM and increased with grade for grade II and anaplastic astrocytomas, but was highly variable for glioblastomas. Higher [Cho] and [Cr] correlated with low lipid and lactate (P < 0.05), indicating a dilution of metabolite concentrations due to necrosis in high-grade tumors. Metabolite peak area ratios showed no correlation with lipids and mI/Cho (at TE = 30 ms), and Cr/Cho (at TE = 136 ms) best correlated with tumor grade. The quantified lipid, macromolecule, and lactate levels increased with grade of tumor, consistent with progression from hypoxia to necrosis. Quantification of lipids and macromolecules at short TE provided a good marker for tumor grade, and a scatter plot of the sum of alanine, lactate, and delta 1.3 lipid signals vs. mI/Cho provided a simple way to separate most tumors by type and grade.

In vivo GABA+ measurement at 1.5T using a PRESS-localized double quantum filter.

A point-resolved spectroscopy (PRESS)-localized double quantum filter was implemented on a 1.5T clinical scanner for the estimation of gamma-amino butyric acid (GABA) concentrations in vivo. Several calibrations were found to be necessary for consistent results to be obtained. The apparent filter yield was approximately 38%; filter strength was sufficient to reduce the singlet metabolite peaks in vivo to below the level of the noise. Metabolite-nulled experiments were performed, which confirmed that significant overlap occurred between macromolecule signals and the GABA resonance at 3.1 ppm. Although the multiplet arm at 2.9 ppm was confirmed to be relatively free of contamination with macromolecules, some contribution from these and from peptides is likely to remain; therefore, the term GABA+ is used. GABA+ concentrations were estimated relative to creatine (Cr) at the same echo time (TE) in a group of controls, studied on two occasions. The GABA+ concentration in 35-ml regions of interest (ROIs) in the occipital lobe was found to be 1.4 +/- 0.2 mM, with scan-rescan repeatability of 38%.

Brain metabolite changes in cortical grey and normal-appearing white matter in clinically early relapsing-remitting multiple sclerosis.

While much work has concentrated on focal white matter (WM) lesions in multiple sclerosis, there is growing evidence to suggest that normal-appearing WM (NAWM) and grey matter (GM) are also involved in the disease process. This study investigated multiple sclerosis disease effects on NAWM and cortical GM (CGM) metabolite concentrations, and the relationships between these metabolite concentrations and clinical impairment. Proton magnetic resonance spectroscopic imaging ((1)H-MRSI) data acquired using point resolved spectroscopic (PRESS) localization (echo time 30 ms, repetition time 3000 ms, nominal voxel volume 2.3 ml) from 27 relapsing-remitting multiple sclerosis and 29 normal control (NC) subjects were processed using LCModel to estimate metabolite concentrations in millimoles per litre. (1)H-MRSI voxel tissue contents were estimated using SPM99 tissue and semi-automatic lesion segmentations of three-dimensional fast spoiled gradient recall scans acquired during the same scanning session. NAWM and CGM metabolite concentrations estimated were: choline-containing compounds (Cho); creatine and phosphocreatine (Cr); myo-inositol (Ins); N-acetyl-aspartate plus N-acetyl-aspartyl-glutamate (tNAA); and glutamate plus glutamine (Glx). CGM data came from 24 of the multiple sclerosis (mean age 35.2 years, mean disease duration 1.7 years) and 25 of the NC (mean age 34.9 years) subjects. NAWM data came from 25 of the multiple sclerosis (mean age 35.0 years, mean disease duration 1.7 years) and 28 of the NC (mean age 36.7 years) subjects. Metabolite concentrations were compared between multiple sclerosis and NC subjects using multiple (linear) regression models allowing for age, gender, (1)H-MRSI voxel tissue and CSF contents, and brain parenchymal volume. At a significance level of P < 0.05, CGM Cho, CGM and NAWM tNAA, and CGM Glx were all significantly reduced, and NAWM Ins was significantly elevated. Spearman correlations of multiple sclerosis functional composite scores with tissue metabolite concentrations were significant for the following: CGM Cr (r(s) = 0.524, P = 0.009), CGM Glx (r(s) = 0.580, P = 0.003) and NAWM Ins (r(s) = -0.559, P = 0.004). These results indicate that metabolite changes in NAWM and CGM can be detected early in the clinical course of multiple sclerosis, and that some of these changes relate to clinical status. The correlation of clinical impairment with CGM Cr and Glx but not tNAA suggests that it is more closely associated with neuronal metabolic dysfunction rather than loss in clinically early relapsing-remitting multiple sclerosis. The correlation of clinical impairment with a raised NAWM Ins may indicate that glial proliferation also relates to function at this stage of the disease.

Quantitative 1H MRS imaging 14 years after presenting with a clinically isolated syndrome suggestive of multiple sclerosis.

clinically isolated syndromes (CIS) are events suggestive for emerging multiple sclerosis (MS). A majority of patients develop MS within months or years whilst others remain clinically isolated. The goal of this study was to investigate whether biochemical metabolites detectable by 'H magnetic resonance spectroscopy (MRS) may serve to distinguish between these two groups. We investigated 41 patients 14 years after presentation with a CIS and 21 controls with combined quantitative short echo 'H MRS and magnetic resonance imaging (MRI) and assessed disability according to the Expanded Disability Status Scale (EDSS). At follow-up, 32 had developed MS, and 9 still had CIS. Compared with controls, MS patients demonstrated significantly higher concentrations of myo-inositol (Ins) in normal appearing white matter (NAWM) and lesions. Lesions also demonstrated a reduced N-acetyl-aspartate (NAA) level and an increase in choline-containing compounds (Cho). The NAWM Ins concentration was correlated with EDSS (r = 0.48, p = 0.005). MS normal appearing cortical grey matter (CGM) exhibited a decreased NAA. Patients who remained CIS did not differ significantly from controls in any MRS measure. Metabolite changes in normal appearing white and grey matter in MS indicate diffuse involvement of the entire MS brain, which was not seen in the persisting CIS patients. Elevated Ins in MS NAWM appeared functionally relevant It may indicate glial cell proliferation or gliosis.

A comparison of some metabolic effects of N-methylaspartate stereoisomers, glutamate and depolarization: a multinuclear MRS study.

Exposure of guinea pig brain slices to low concentrations (10 microM) of NMDA caused decreases in PCr and ATP within 30 min, with a slower decrease in NAA and increase in lactate, both detectable after 1 h. Exposure to NMDA for over 1 h or at higher concentrations caused further increases in lactate and decreases in NAA, with no further change in PCr or ATP. The L-isomer, NMLA, and the racemic mixture, NMDLA, caused similar changes in lactate and NAA, but both produced greater decreases in the energy state than NMDA, similar to those caused by prolonged exposure to glutamate. MK-801 prevented the changes in the energy state caused by NMDA, but not those caused by NMLA or by glutamate. The results are compared to previous studies on depolarization and discussed in terms of the role of the NMDA sub-type of glutamate receptor in the excitotoxic hypothesis of neuronal degeneration.

Characterization of the oxygenated intermediate of the thermophilic cytochrome P450 CYP119.

Using UV-Vis, resonance Raman, and EPR spectroscopy we have studied the properties of the oxygenated ferrous cytochrome P450 from Sulfolobus solfataricus, (CYP119). The recently determined crystal structure of CYP119 is compared with other available structures of P450s, and detailed structural and spectroscopic analyses are reported. With several structural similarities to CYP102, such as in-plane iron position and a shorter iron-proximal ligand bond, CYP119 shows low-spin conformation preference in the ferric form and partially in the ferrous form at low temperatures. These structural features can explain the fast autoxidation of the oxyferrous complex of CYP119. Finally, we report the first UV-Vis and EPR spectra of the cryoradiolytically reduced oxygenated intermediate of CYP119. The primary reduced intermediate, a hydroperoxo-ferric complex of CYP119, undergoes a 'peroxide shunt' pathway during gradual annealing at 170-195 K and returns to the low-spin ferric form.

Analysis of residual trifluoroacetic acid in a phosphate-buffered saline matrix by ion chromatography with suppressed conductivity detection.

As part of the formulation of a cell-based pharmaceutical product, cells were harvested from mice and incubated in a cocktail containing cell culture media and high levels of trifluoroacetic acid (TFA). The cells were washed with a phosphate-buffered saline solution to remove residual cell culture media and other reagents before the cells were infused back into the mice from which they originated. Because of the potentially toxic nature of the TFA, the cells were washed multiple times and the final wash was monitored for residual TFA in order to demonstrate the efficient removal of the reagent before the cell product could be reintroduced into the test animal. This report describes the method that was developed incorporating anion-exchange chromatography with suppressed conductivity detection for the analysis of residual TFA (down to 50 ng/ml) in the presence of high concentrations of phosphate and chloride interferences. The ultimate sensitivity of the method was improved by selectively removing halide anions using a silver cartridge before sample analysis. The method proved to be rugged and reproducible enough to be validated and used to monitor residual TFA levels in cell washes in support of an acute toxicological study. Results demonstrating the method's sensitivity, selectivity, precision and linearity were reported.

In vivo short echo time 1H-magnetic resonance spectroscopic imaging (MRSI) of the temporal lobes.

Two different methodologies for obtaining PRESS-localized magnetic resonance spectroscopic imaging (MRSI) data from the mesial and lateral temporal lobes were investigated. The study used short echo times (30 ms) and long repetition times (3000 ms) to minimize relaxation effects. Inhomogeneity and spectral distortions from the proximity of the temporal bones precluded the attainment of consistently good-quality data from both temporal lobes at once. Even when the right and left temporal lobes were studied separately, distortions often disturbed spectra from the anterior lateral temporal lobe. Quantitative analysis using LCModel was therefore performed only on the posterior lateral temporal lobe, and the posterior, middle, and anterior mesial temporal lobe. No significant left-right differences in metabolite content were found in a series of 10 controls. Significantly higher concentrations of myoinositol and choline were found in the anterior mesial temporal lobe, even when grey matter content was included as a covariate. The concentration of N-acetyl aspartate plus N-acetyl aspartyl glutamate (NAc) was not found to vary significantly along the length of the hippocampus. The previously observed lower anterior ratios of NAA to creatine plus choline (NAA/(Cr + Cho) may instead have been due to higher anterior choline. Large differences in metabolite concentrations were seen between posterior lateral temporal lobe (predominantly subcortical white matter) and the posterior mesial temporal lobe, most notably lower creatine, glutamate/glutamine, and myo-inositol, and higher NAA/(Cr + Cho) in the lateral than mesial temporal lobe. This pattern was similar to that previously seen for grey/white matter differences in the frontal, parietal and occipital regions.

Preliminary evidence for neuronal damage in cortical grey matter and normal appearing white matter in short duration relapsing-remitting multiple sclerosis: a quantitative MR spectroscopic imaging study.

Neuronal damage and loss is likely to underlie irreversible disability in multiple sclerosis (MS). The time of onset, location and extent of neuronal damage in early disease are all uncertain. To explore this issue 16 patients with short duration, mild relapsing-remitting disease (mean disease duration 1.8 years, median EDSS 1) were studied using short echo time proton magnetic resonance spectroscopic imaging (1H-MRSI) to quantify the concentration of the neuronal marker N-acetyl-aspartate (NAA). The data were compared with those from 12 age-matched controls. 1H-MRSI was obtained from a 1.5-cm-thick slice just above the lateral ventricles. The Linear Combination (LC) Model combined with locally developed software allowed automated measurement of absolute metabolite concentrations from lesions, normal-appearing white matter (NAWM) and cortical grey matter (CGM). MS CGM exhibited significantly lower NAA (P = 0.01) and myo-inositol (P = 0.04) than control CGM. MS NAWM exhibited a lower concentration of NAA (P = 0.01) and increased myo-inositol (P = 0.03) than control white matter. More marked reductions in NAA and increases in myo-inositol were seen in lesions. The reduced NAA in MS CGM and NAWM suggest that mild but widespread neuronal dysfunction or loss occurs early in the course of relapsing-remitting MS. This preliminary finding should be confirmed in a larger cohort, and follow-up studies are also needed to determine the prognostic and pathophysiological significance of these early changes.

Quantitative short echo time proton magnetic resonance spectroscopic imaging study of malformations of cortical development causing epilepsy.

In patients with malformations of cortical development (MCD), widespread structural abnormalities of the brain have been demonstrated using volumetric MRI, and associated with poor post-surgical outcome in patients with localization-related epilepsy. Proton magnetic resonance spectroscopic imaging (1H-MRSI) studies permit the non-invasive measurement of concentrations of a variety of cerebral metabolites implicated in cerebral structure and function. There is a dearth of quantitative 1H-MRSI studies of MCD. Ten controls and 10 patients with localization-related epilepsy who were found to have MCD on high resolution MRI underwent 1H-MRSI on a 1.5 T GE Signa scanner [TE (echo time) = 30 ms, TR (repetition time) = 3 s]. In all patients, the axial area studied contained lesional and perilesional tissue. In seven unilaterally affected patients, the area studied contained also apparently normal contralateral grey and white matter; in three patients with bilateral but asymmetrical MCD, it contained visually normal and abnormal tissue from both hemispheres. N-acetyl aspartate + N-acetyl aspartyl glutamate (NAA), creatine + phosphocreatine (Cr), choline-containing compounds (Cho), glutamate + glutamine (Glx) and myo-inositol (Ins) were automatically quantified in voxels covering these different regions. Metabolite concentrations were corrected for CSF content and correlated with the grey and white matter of the MRSI voxels. In control subjects, there were significant positive correlations between grey matter content and concentrations of NAA, Glx, Ins and Cr. Compared with a normal range that took grey matter content into account, defined as the control mean +/- 2 SD, all lesions but one showed metabolic abnormalities. The most common abnormality was a decrease in NAA, but findings were heterogeneous and there was increased NAA in one lesion. Perilesional tissue was abnormal in eight patients, with increased NAA in three. Tissue contralateral to the main MCD was abnormal in all three patients with bilateral but asymmetrical MCD, and in six of the seven apparently unilaterally affected patients. Spectroscopic grey and white matter abnormalities in patients with MCD exceeded the apparently focal abnormality shown by MRI, indicating widespread abnormalities of cerebral function.

Quantitative analysis of short echo time (1)H-MRSI of cerebral gray and white matter.

Quantitative analysis of (1)H-magnetic resonance spectroscopic imaging (MRSI) data was developed using the user-independent spectral analysis routine LCModel. Tissue segmentation was performed using statistical parametric mapping software (SPM 96), and the results were used to correct for cerebrospinal fluid contamination. A correction was developed for the imperfections in the spectroscopic excitation profile in order to improve the uniformity of metabolite images. After validation in phantoms, these techniques were applied to study differences in metabolite concentrations between gray and white matter in normal volunteers (n = 13). A positive correlation was found between concentration and gray matter content for most metabolites studied. The estimated ratios of metabolite concentration in gray vs. white matter were: N-acetyl aspartate + N-acetyl aspartyl glutamate (NAc) = 1.16+/- 0.11; creatine = 1.7+/-0.3; glutamate + glutamine = 2.4+/-0.5; myo-inositol = 1.6+/-0.3; choline = 0.9+/-0.2. The ratio of NAc/Cr was negatively correlated with gray matter content: gray/white = 0.69 +/-0.08. These methods will be useful in the evaluation of metabolite concentrations in MRSI voxels with mixed tissue composition in patient groups.