Proton magnetic resonance spectroscopy ( 1 HMRS) is an in vivo brain imaging method that can be used to investigate psychotropic drug mechanism of action. This study evaluated baseline 1 HMRS spectra of bipolar depressed patients and whether the level of cerebral metabolites changed after an open trial of lamotrigine, an anti-glutamatergic mood stabilizer. Twenty-three bipolar depressed and 12 control subjects underwent a MRS scan of the anterior cingulate/medial prefrontal cortex. The scan was performed on a GE whole-body 1.5 T MRI scanner using single-voxel PRESS (TE/TR ¼ 30/3000 ms, 3 Â 3 Â 3 cm 3 and post-processed offline with LCModel. Baseline CSF-corrected absolute concentrations of glutamate + glutamine ([Glx]), glutamate ([Glu]), and creatine + phosphocreatine ([Cr]) were significantly higher in bipolar depressed subjects vs healthy controls. The non-melancholic subtype had significantly higher baseline [Glx] and [Glu] levels than the melancholic subtype. Remission with lamotrigine was associated with significantly lower post-treatment glutamine ([Gln]) in comparison to non-remission. These data suggest that non-melancholic bipolar depression is characterized by increased glutamate coupled with increased energy expenditure. Lamotrigine appears to reduce glutamine levels associated with treatment remission. Further study is encouraged to determine if these MR spectroscopic markers can delineate drug mechanism of action and subsequent treatment response.

Proton (1H) MRS enables non-invasive biochemical assay with the potential to characterize malignant, benign and healthy breast tissues. In vitro studies using perchloric acid extracts and ex vivo magic angle spinning spectroscopy of intact biopsy tissues have been used to identify detectable metabolic alterations in breast cancer. The challenges of 1H MRS in vivo include low sensitivity and significant overlap of resonances due to limited chemical shift dispersion and significant inhomogeneous broadening at most clinical magnetic field strengths. Improvement in spectral resolution can be achieved in vivo and in vitro by recording the MR spectra spread over more than one dimension, thus facilitating unambiguous assignment of metabolite and lipid resonances in breast cancer. This article reviews the recent progress with two-dimensional MRS of breast cancer in vitro, ex vivo and in vivo. The discussion includes unambiguous detection of saturated and unsaturated fatty acids, as well as choline-containing groups such as free choline, phosphocholine, glycerophosphocholine and ethanolamines using two-dimensional MRS. In addition, characterization of invasive ductal carcinomas and healthy fatty/glandular breast tissues non-invasively using the classification and regression tree (CART) analysis of two-dimensional MRS data is reviewed.

The major goal of this work was to characterize invasive ductal carcinoma and healthy fatty breast tissues noninvasively using the classification and regression tree analysis (CART) of 2D MR spectral data. 2D L-COSY spectra were acquired in 14 invasive breast carcinoma and 21 healthy fatty breasts using a GE 1.5 Tesla MRI/MRS scanner equipped with a 2-channel phased-array breast MR coil. The 2D spectra were recorded in approximately 10 minutes using a minimum voxel size of 1 ml without any water suppression technique. For healthy breasts, spectra were acquired from at least one fatty region. 2D L-COSY spectra were recorded in a total of 43 voxels. Five diagonal and six cross peak volumes were integrated and at least eighteen ratios were selected as potential features for the statistical method, namely CART. The 2D L-COSY data showed a significant increase for the majority of these ratios in invasive breast carcinomas compared to healthy fatty tissues. Better accuracy of identifying carcinomas and fatty tissues is reported using CART analysis of different combinations of ratios calculated from the relative levels of water, choline, and saturated and unsaturated lipids. This is a first report on the statistical classification of 2D L-COSY in human breast carcinomas in vivo.

Purpose: To measure cerebral metabolites in brains of human immunodeficiency virus (HIV)-infected patients using two-dimensional (2D) proton ( 1 H) magnetic resonance spectroscopy (MRS), which enables more sensitive detection of metabolites at lower concentrations and delineation of the components of the different choline (Ch) groups in the frequency domain when compared to one dimensional (1D) 1 H-MRS. Materials and Methods:We examined metabolite/creatine (Cr) and metabolite/Ch ratios in the left frontal brain of 10 HIV-infected (mean age 13.7 Ϯ 4.7 years) and 11 control (mean age 15.3 Ϯ 4.6 years) adolescents and children using 2D localized chemical shift correlated spectroscopy (L-COSY). The integrated volume under each 2D metabolite peak was calculated with reference to the diagonal creatine methyl peak (Cr_d) or the diagonal choline trimethylamine peak (Ch_d). Results:In the HIV-infected patients, myoinositol (mI)/ Cr_d (P ϭ 0.009) and mI/Ch_d (P ϭ 0.006) were elevated. The ratios of the following metabolites were also significantly elevated (P Ͻ 0.05): mI-Ch/Cr_d, ␥-aminobutyrate (GABA)/ Cr_d , GABA/Ch_d, threonine-lactate (Thr-Lac)/ Cr_d, Thr-Lac/Ch_d, and N-acetyl aspartate (NAA)/Cr_d. Conclusion:We have demonstrated for the first time the feasibility of 2D-MRS in HIV-infected children and adolescents to assess cerebral metabolites and found elevated mI and elevated GABA, in the left frontal brain of clinically stable HIV-infected patients. A larger study population is needed to confirm these pilot GABA findings.

Localized 2D shift-correlated MR spectra (L-COSY) of human prostates were recorded using an endorectal “receive” coil. Typically, 4 ml voxels were placed in the peripheral zones of the prostate. Seven healthy volunteers and one BPH patient have participated in this study so far. The total acquisition time for a 2D L-COSY was approximately 20 minutes. A 1.5 Tesla GE scanner with a body coil for RF transmission and a pelvic phased-array coil combined with a disposable rectal coil for reception was used. The 2D L-COSY spectra showed cross peaks due to citrate, spermine and occasionally choline, creatine and lipids. The 2D cross peaks due to both the multiplets of spermine were clearly resolved from choline and creatine which has been a major problem with the conventional MR spectroscopic techniques. In contrast to 2D JPRESS, improved spectral dispersion, less crowded 2D cross peaks and unequivocal detection of both multiplets of spermine were monitored in 2D L-COSY. Pilot results suggest that localized 2D L-COSY can be successfully implemented in human prostates on a clinical scanner.

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