Functional MRI is convenient for neurological and psychiatric diseases research. However, physiological and biochemical mechanisms involved in hemodynamic response (HR) processes are still subjects of studies. HR and metabolic processes are closely related. To reveal these relations, dynamic spectroscopy was used [1]. Early stage schizophrenia was characterized with decrease of hemodynamic response function (HRF) [2] and altered NAA kinetics after neurostimulation [1]. HRF contains spin-spin relaxation (T2*) and water concentration (C) information. The purpose of this study is to separate T2* and C contributions to water signal changes in premotor cortex activated by a single stimulus in the norm and in early stage schizophrenia using dynamic spectroscopy.

The subjects of study were 8 right-handed healthy subjects and 6 right-handed and age-matched patients with early stage schizophrenia. Philips Achieva 3.0T and 8-chanel SENSE Head coil were used. Standard anatomic examination and fMRI study (GE-EPI, TE=35ms, TR=3000ms) with single stimulus (pressing a special button on presentation of sound signal) were conducted. Spectroscopic voxel (PRESS, TE=30ms, TR=3000ms, size 20x10x15 mm3) was positioned to activated zone of premotor cortex (Fig.1). Dynamic spectroscopy was performed, when FID signals were recorded at the moments t = 0, 3, 6, 9, 12, 15, 18 and 21 s after pressing the button with a right hand forefinger. For each t, 97 FIDs were acquired, resulting in 776 FIDs for every subject. FIDs were processed individually: FT, phase correction, water peak amplitude and area quantitation were performed. Amplitude and area of water signal for each time point were averaged and normalized on initial (t=0) values.

Statistical analysis was performed using Mann-Whitney criterion.

Formulas describing relationship between Amplitude and Area of water peak with T2* and C values were derived by FID signal interpreted in discrete form followed by Discrete FT application to it. For steady-state phase-corrected spectrum, signal intensity can be estimated as:

$$$Ampl=A*C*exp(-TE/(T_2^*))*[exp(-αN/BW)-1]/([exp(-α/BW)-1])$$$

$$$Area=A*C*exp[(-TE/(T_2^*))*N]$$$

where α=1/T2*, BW–bandwidth, A–const, C–MR-detectible concentration, N–number of sample points of water signal.

C(t) and T2*(t) values were calculated using these formulas. For the norm, T2*(t) and C(t) with HRF(t) (obtained in [2]) are shown in Fig. 2. At maximum of HRF (t=6s) we observe statistically significant (p<0.01) reduction of C that returns to its initial value after 3s, and T2* increase (p<0.01) with an undershoot (p<0.05) after 3s. No statistically significant reduction (p=0.07) of C at (t=6s) as well as no increase of C at (t=9s) in schizophrenia, at this time point C differs (p<0.05) between norm and schizophrenia (Fig.3). T2* decrease (t=9s) in schizophrenia is smoothed: there is no undershoot and T2* is ~1% higher (p<0.01) than in the norm (Fig.4).

In the norm at (t=6s) after single stimulus blood flow increases in activated cortex. According to Monro-Kellie hypothesis, the MR-undetectable (not irradiated by excitation pulse of PRESS) water from blood flow partly replaces MR-detectable water located in voxel before. The next spectrum of dynamic study reveals this water at (t=9s) after stimulus. This returns C to its initial value. Our estimation (based on neuronal glucose metabolism rate [3]) shows that the volume of metabolic water is 1.5–2 orders of magnitude less than the C change revealed in present study.

T2* maximum at the point of HRF maximum is caused by increase of [oxiHb/deoxiHb]. The maximal increase of T2* obtained in this study using spin-echo (PRESS) is ~1%, while maximal increase of HRF obtained using gradient echo (GE-EPI) [2] is ~3.5%. This agrees with [4] ([GE-BOLD]/[SE-BOLD]~3.5).

The T2* undershoot at (t=9s) in the norm is caused by blood deoxiHb accumulation [5]. A smoother Т2* decrease at (t=9s) in schizophrenia contributes to real T2* contrast decrease. This agrees with decreased HRF in schizophrenia [2].

Absence of C decrease and T2* undershoot in schizophrenia reflects less inflow of MR-undetectable water protons and [oxyHb/deoxiHb] increase as compared to the norm. It might reflect decreased vasodilation. Since vasodilation is connected to EAAT glutamate transporters activity and glutamate-to-receptor binding in neurons and astrocytes [6], results of this study point to glutamate transport and receptor binding deviations in schizophrenia.

Using dynamic spectroscopy we separated T2* and C of water in activated cortex. Schizophrenia-induced differences in these parameters after single stimulus are likely to be caused by reduced vasodilation.