Use of tissue water as a concentration reference for proton spectroscopic imaging

Intrascan subject movement in clinical MR spectroscopic examinations may result in inconsistent water suppression that distorts the metabolite signals, frame-to-frame variations in spectral phase and frequency, and consequent reductions in the signal-to-noise ratio due to destructive averaging. Frameto-frame phase/frequency corrections, although reported to be successful in achieving constructive averaging, rely on consistent water suppression, which may be difficult in the presence of intrascan motion. In this study, motion correction using nonwater-suppressed data acquisition is proposed to overcome the above difficulties. The time-domain matrix-pencil postprocessing method was used to extract water signals from the non-water-suppressed spectroscopic data, followed by phase and frequency Inevitable subject motions during successive data acquisition in magnetic resonance spectroscopy (MRS) may cause signal loss because of two major mechanisms (1-4). First, motion-induced magnetic field drifts may lead to frequency shift over multiple MRS acquisition frames. Second, subject movements in the presence of the spoiler gradients may result in inconsistent phase variations among acquisition frames. In conventional MRS studies, data from all acquisition frames are simply averaged, and therefore the destructively averaged spectrum would be affected by signal-to-noise ratio (SNR) attenuation and spectral shape distortion because of frame-to-frame phase/ frequency variations. It has been shown that, by performing frame-by-frame corrections for the intrascan phase/ frequency variations, the constructively averaged MRS data exhibit significantly improved SNR and spectral quality (1-8). The search for an effective intrascan phase/frequency correction method is thus an active field of research for in vivo MRS.Over the past decades, several methods have been proposed to measure the intrascan phase/frequency variations in MRS scans in order to perform constructive averaging (1,2,4-6). In one of these methods, the non-water-suppressed (NWS) free induction decay and water-suppressed (WS) MRS data were acquired in an interleaved manner (2). Intrascan phase/frequency variations estimated from the NWS free induction decay were used to correct the WS MRS data. In this approach, however, the phase variations in WS MRS data are corrected by values estimated at different time points. Therefore, the effectiveness of the phase correction might be suboptimal, particularly in the presence of abrupt intrascan movements.Alternatively, the phase variations induced by intrascan motion could be measured on a frame-by-frame basis directly from the residual water signals of WS MRS data (1,4). However, even though the information estimated directly from the WS MRS data better reflects the instant phase variation in comparison to the interleaved free induction decay-based measurements, this approach has two main limitations: First, the residual water signals in WS MRS data have low SNR that limits the accuracy of frameby-frame phase estimation (1). ...

Glutamine plus glutamate (Glx), as well as N-acetylaspartate compounds (NAAc, N-acetylaspartate plus N-acetyl-aspartyl-glutamate), a marker of neuronal viability, can be quantified with proton magnetic resonance spectroscopy ( 1 H-MRS). We used 1 H-MRS imaging to assess Glx and NAAc, as well as totalcholine (glycerophospho-choline plus phospho-choline), myo-inositol and total-creatine (creatine plus phosphocreatine) from an axial supraventricular slab of gray matter (GM, medial-frontal and medial-parietal) and white matter (WM, bilateral-frontal and bilateralparietal) voxels. Schizophrenia subjects (N = 104) and healthy controls (N = 97) with a broad age range (16 to 65) were studied. In schizophrenia, Glx was increased in GM (P < .001) and WM (P = .01), regardless of age. However, with greater age, NAAc increased in GM (P < .001) but decreased in WM (P < .001) in schizophrenia. In patients, total creatine decreased with age in WM (P < .001). Finally, overall cognitive score correlated positively with WM neurometabolites in controls but negatively in the schizophrenia group (NAAc, P < .001; and creatine [only younger], P < .001). We speculate the results support an ongoing process of increased glutamate metabolism in schizophrenia. Later in the illness, disease progression is suggested by increased cortical compaction without neuronal loss (elevated NAAc) and reduced axonal integrity (lower NAAc). Furthermore, this process is associated with fundamentally altered relationships between neurometabolite concentrations and cognitive function in schizophrenia.

Schizophrenia is associated with abnormalities in the structure and functioning of white matter, but the underlying neuropathology is unclear. We hypothesized that increased tryptophan degradation in the kynurenine pathway could be associated with white matter microstructure and biochemistry, potentially contributing to white matter abnormalities in schizophrenia. To test this, fasting plasma samples were obtained from 37 schizophrenia patients and 38 healthy controls and levels of total tryptophan and its metabolite kynurenine were assessed. The ratio of kynurenine to tryptophan was used as an index of tryptophan catabolic activity in this pathway. White matter structure and function were assessed by diffusion tensor imaging (DTI) and 1 H magnetic resonance spectroscopy (MRS). Tryptophan levels were significantly lower (po0.001), and kynurenine/tryptophan ratios were correspondingly higher (p = 0.018) in patients compared with controls. In patients, lower plasma tryptophan levels corresponded to lower structural integrity (DTI fractional anisotropy) (r = 0.347, p = 0.038). In both patients and controls, the kynurenine/tryptophan ratio was inversely correlated with frontal white matter glutamate level (r = − 0.391 and − 0.350 respectively, p = 0.024 and 0.036). These results provide initial evidence implicating abnormal tryptophan/ kynurenine pathway activity in changes to white matter integrity and white matter glutamate in schizophrenia.