Shang-Yueh Tsai

Sensitivity-Encoded (SENSE) Proton Echo-Planar Spectroscopic Imaging (PEPSI) in the Human Brain

Magnetic resonance spectroscopic imaging (MRSI) provides spatially resolved metabolite information that is invaluable for both neuroscience studies and clinical applications. However, lengthy data acquisition times, which are a result of time‐consuming phase encoding, represent a major challenge for MRSI. Fast MRSI pulse sequences that use echo‐planar readout gradients, such as proton echo‐planar spectroscopic imaging (PEPSI), are capable of fast spectral‐spatial encoding and thus enable acceleration of image acquisition times. Combining PEPSI with recent advances in parallel MRI utilizing RF coil arrays can further accelerate MRSI data acquisition. Here we investigate the feasibility of ultrafast spectroscopic imaging at high field (3T and 4T) by combining PEPSI with sensitivity‐encoded (SENSE) MRI using eight‐channel head coil arrays. We show that the acquisition of single‐average SENSE‐PEPSI data at a short TE (15 ms) can be accelerated to 32 s or less, depending on the field strength, to obtain metabolic images of choline (Cho), creatine (Cre), N‐acetyl‐aspartate (NAA), and J‐coupled metabolites (e.g., glutamate (Glu) and inositol (Ino)) with acceptable spectral quality and localization. The experimentally measured reductions in signal‐to‐noise ratio (SNR) and Cramer‐Rao lower bounds (CRLBs) of metabolite resonances were well explained by both the g‐factor and reduced measurement times. Thus, this technology is a promising means of reducing the scan times of 3D acquisitions and time‐resolved 2D measurements. Magn Reson Med 57:249–257, 2007.

Accelerated proton echo planar spectroscopic imaging (PEPSI) using GRAPPA with a 32‐channel phased‐array coil

Parallel imaging has been demonstrated to reduce the encoding time of MR spectroscopic imaging (MRSI). Here we investigate up to 5‐fold acceleration of 2D proton echo planar spectroscopic imaging (PEPSI) at 3T using generalized autocalibrating partial parallel acquisition (GRAPPA) with a 32‐channel coil array, 1.5 cm3 voxel size, TR/TE of 15/2000 ms, and 2.1 Hz spectral resolution. Compared to an 8‐channel array, the smaller RF coil elements in this 32‐channel array provided a 3.1‐fold and 2.8‐fold increase in signal‐to‐noise ratio (SNR) in the peripheral region and the central region, respectively, and more spatial modulated information. Comparison of sensitivity‐encoding (SENSE) and GRAPPA reconstruction using an 8‐channel array showed that both methods yielded similar quantitative metabolite measures (P > 0.1). Concentration values of N‐acetyl‐aspartate (NAA), total creatine (tCr), choline (Cho), myo‐inositol (mI), and the sum of glutamate and glutamine (Glx) for both methods were consistent with previous studies. Using the 32‐channel array coil the mean Cramer–Rao lower bounds (CRLB) were less than 8% for NAA, tCr, and Cho and less than 15% for mI and Glx at 2‐fold acceleration. At 4‐fold acceleration the mean CRLB for NAA, tCr, and Cho was less than 11%. In conclusion, the use of a 32‐channel coil array and GRAPPA reconstruction can significantly reduce the measurement time for mapping brain metabolites. Magn Reson Med 59:989–998, 2008.

Single-shot magnetic resonance spectroscopic imaging with partial parallel imaging

A magnetic resonance spectroscopic imaging (MRSI) pulse sequence based on proton–echo‐planar‐spectroscopic‐imaging (PEPSI) is introduced that measures two‐dimensional metabolite maps in a single excitation. Echo‐planar spatial–spectral encoding was combined with interleaved phase encoding and parallel imaging using SENSE to reconstruct absorption mode spectra. The symmetrical k‐space trajectory compensates phase errors due to convolution of spatial and spectral encoding. Single‐shot MRSI at short TE was evaluated in phantoms and in vivo on a 3‐T whole‐body scanner equipped with a 12‐channel array coil. Four‐step interleaved phase encoding and fourfold SENSE acceleration were used to encode a 16 × 16 spatial matrix with a 390‐Hz spectral width. Comparison with conventional PEPSI and PEPSI with fourfold SENSE acceleration demonstrated comparable sensitivity per unit time when taking into account g‐factor–related noise increases and differences in sampling efficiency. LCModel fitting enabled quantification of inositol, choline, creatine, and N‐acetyl‐aspartate (NAA) in vivo with concentration values in the ranges measured with conventional PEPSI and SENSE‐accelerated PEPSI. Cramer–Rao lower bounds were comparable to those obtained with conventional SENSE‐accelerated PEPSI at the same voxel size and measurement time. This single‐shot MRSI method is therefore suitable for applications that require high temporal resolution to monitor temporal dynamics or to reduce sensitivity to tissue movement. Magn Reson Med, 2009.

Accelerated short-TE 3D proton echo-planar spectroscopic imaging using 2D-SENSE with a 32-channel array coil.

MR spectroscopic imaging (MRSI) with whole brain coverage in clinically feasible acquisition times still remains a major challenge. A combination of MRSI with parallel imaging has shown promise to reduce the long encoding times and 2D acceleration with a large array coil is expected to provide high acceleration capability. In this work a very high‐speed method for 3D‐MRSI based on the combination of proton echo planar spectroscopic imaging (PEPSI) with regularized 2D‐SENSE reconstruction is developed. Regularization was performed by constraining the singular value decomposition of the encoding matrix to reduce the effect of low‐value and overlapped coil sensitivities. The effects of spectral heterogeneity and discontinuities in coil sensitivity across the spectroscopic voxels were minimized by unaliasing the point spread function. As a result the contamination from extracranial lipids was reduced 1.6‐fold on average compared to standard SENSE. We show that the acquisition of short‐TE (15 ms) 3D‐PEPSI at 3 T with a 32 × 32 × 8 spatial matrix using a 32‐channel array coil can be accelerated 8‐fold (R = 4 × 2) along y‐z to achieve a minimum acquisition time of 1 min. Maps of the concentrations of N‐acetyl‐aspartate, creatine, choline, and glutamate were obtained with moderate reduction in spatial‐spectral quality. The short acquisition time makes the method suitable for volumetric metabolite mapping in clinical studies. Magn Reson Med, 2007.

Fast mapping of the T2 relaxation time of cerebral metabolites using proton echo-planar spectroscopic imaging (PEPSI).

Metabolite T2 is necessary for accurate quantification of the absolute concentration of metabolites using long‐echo‐time (TE) acquisition schemes. However, lengthy data acquisition times pose a major challenge to mapping metabolite T2. In this study we used proton echo‐planar spectroscopic imaging (PEPSI) at 3T to obtain fast T2 maps of three major cerebral metabolites: N‐acetyl‐aspartate (NAA), creatine (Cre), and choline (Cho). We showed that PEPSI spectra matched T2 values obtained using single‐voxel spectroscopy (SVS). Data acquisition for 2D metabolite maps with a voxel volume of 0.95 ml (32 × 32 image matrix) can be completed in 25 min using five TEs and eight averages. A sufficient spectral signal‐to‐noise ratio (SNR) for T2 estimation was validated by high Pearsons correlation coefficients between logarithmic MR signals and TEs (R2 = 0.98, 0.97, and 0.95 for NAA, Cre, and Cho, respectively). In agreement with previous studies, we found that the T2 values of NAA, but not Cre and Cho, were significantly different between gray matter (GM) and white matter (WM; P < 0.001). The difference between the T2 estimates of the PEPSI and SVS scans was less than 9%. Consistent spatial distributions of T2 were found in six healthy subjects, and disagreement among subjects was less than 10%. In summary, the PEPSI technique is a robust method to obtain fast mapping of metabolite T2. Magn Reson Med 57:859–865, 2007.

Reduced hippocampal glutamate-glutamine levels in irritable bowel syndrome: preliminary findings using magnetic resonance spectroscopy

OBJECTIVES:Enhanced stress responsiveness is an important pathophysiological factor in irritable bowel syndrome (IBS), suggesting the presence of a dysregulated hypothalamic-pituitary-adrenal (HPA) axis. A possible mechanism involves maladaption of the feedback mechanism of the HPA axis. We hypothesized that hippocampus, a key brain region providing inhibitory feedback to the HPA axis, would exhibit reduced excitatory glutamatergic neurotransmission and reduced N-acetyl-aspartate (NAA; a marker of neuronal integrity) levels in IBS patients.METHODS:In this preliminary study, proton magnetic resonance spectroscopy was used to quantify absolute concentrations of metabolites in bilateral hippocampi of 15 IBS patients without significant psychiatric comorbidity and 15 age-matched controls.RESULTS:The main finding was a reduction in hippocampal glutamate–glutamine (Glx) in IBS patients. Furthermore, Glx concentrations were inversely related to emotional stress indicators in patients only. No difference was found between subject groups for other metabolite concentrations, including NAA. However, an elevated myo-inositol (mI)/NAA ratio was found in IBS patients.CONCLUSIONS:Our results provide preliminary evidence for the presence of abnormal hypofunction of hippocampal glutamatergic neurotransmission in IBS patients without psychiatric comorbidity, possibly as a result of the chronic pain. This supports the notion of an imbalance in regulatory brain regions in this subgroup of IBS patients. The inverse relationship between Glx and emotional stress indicators is in agreement with the inhibitory role of hippocampus on the stress system and suggests a sensitization of the mechanism to emotional arousal. The elevated mI/NAA ratio in IBS patients further suggests the presence of hippocampal glial proliferation and remodeling.

Significant feed-forward connectivity revealed by high frequency components of BOLD fMRI signals

Granger causality analysis has been suggested as a method of estimating causal modulation without specifying the direction of information flow a priori. Using BOLD-contrast functional MRI (fMRI) data, such analysis has been typically implemented in the time domain. In this study, we used magnetic resonance inverse imaging, a method of fast fMRI enabled by massively parallel detection allowing up to 10 Hz sampling rate, to investigate the causal modulation at different frequencies up to 5 Hz. Using a visuomotor two-choice reaction-time task, both the spectral decomposition of Granger causality and isolated effective coherence revealed that the BOLD signal at frequency up to 3 Hz can still be used to estimate significant dominant directions of information flow consistent with results from the time-domain Granger causality analysis. We showed the specificity of estimated dominant directions of information flow at high frequencies by contrasting causality estimates using data collected during the visuomotor task and resting state. Our data suggest that hemodynamic responses carry physiological information related to inter-regional modulation at frequency higher than what has been commonly considered.

Sensory gating, inhibition control and gamma oscillations in the human somatosensory cortex

Inhibiting the responses to irrelevant stimuli is an essential component of human cognitive function. Pre-attentive auditory sensory gating (SG), an attenuated neural activation to the second identical stimulus, has been found to be related to the performance of higher-hierarchical brain function. However, it remains unclear whether other cortical regions, such as somatosensory cortex, also possess similar characteristics, or if such a relationship is modality-specific. This study used magnetoencephalography to record neuromagnetic responses to paired-pulse electrical stimulation to median nerve in 22 healthy participants. Somatosensory SG ratio and cortical brain oscillations were obtained and compared with the behavioral performance of inhibition control, as evaluated by somatosensory and auditory Go-Nogo tasks. The results showed that somatosensory P35m SG ratio correlated with behavioral performance of inhibition control. Such relationship was also established in relation to the auditory Go-Nogo task. Finally, a higher frequency value of evoked gamma oscillations was found to relate to a better somatosensory SG ability. In conclusion, our data provided an empirical link between automatic cortical inhibition and behavioral performance of attentive inhibition control. This study invites further research on the relationships among gamma oscillations, neurophysiological indices, and behavioral performance in clinical populations in terms of SG or cortical inhibition.

Short- and long-term quantitation reproducibility of brain metabolites in the medial wall using proton echo planar spectroscopic imaging.

Proton echo planar spectroscopic imaging (PEPSI) is a fast magnetic resonance spectroscopic imaging (MRSI) technique that allows mapping spatial metabolite distributions in the brain. Although the medial wall of the cortex is involved in a wide range of pathological conditions, previous MRSI studies have not focused on this region. To decide the magnitude of metabolic changes to be considered significant in this region, the reproducibility of the method needs to be established. The study aims were to establish the short- and long-term reproducibility of metabolites in the right medial wall and to compare regional differences using a constant short-echo time (TE30) and TE averaging (TEavg) optimized to yield glutamatergic information. 2D sagittal PEPSI was implemented at 3T using a 32 channel head coil. Acquisitions were repeated immediately and after approximately 2 weeks to assess the coefficients of variation (COV). COVs were obtained from eight regions-of-interest (ROIs) of varying size and location. TE30 resulted in better spectral quality and similar or lower quantitation uncertainty for all metabolites except glutamate (Glu). When Glu and glutamine (Gln) were quantified together (Glx) reduced quantitation uncertainty and increased reproducibility was observed for TE30. TEavg resulted in lowered quantitation uncertainty for Glu but in less reliable quantification of several other metabolites. TEavg did not result in a systematically improved short- or long-term reproducibility for Glu. The ROI volume was a major factor influencing reproducibility. For both short- and long-term repetitions, the Glu COVs obtained with TEavg were 5-8% for the large ROIs, 12-17% for the medium sized ROIs and 16-26% for the smaller cingulate ROIs. COVs obtained with TE30 for the less specific Glx were 3-5%, 8-10% and 10-15%. COVs for N-acetyl aspartate, creatine and choline using TE30 with long-term repetition were between 2-10%. Our results show that the cost of more specific glutamatergic information (Glu versus Glx) is the requirement of an increased effect size especially with increasing anatomical specificity. This comes in addition to the loss of sensitivity for other metabolites. Encouraging results were obtained with TE30 compared to other previously reported MRSI studies. The protocols implemented here are reliable and may be used to study disease progression and intervention mechanisms.

Resting‐State Functional Magnetic Resonance Imaging: The Impact of Regression Analysis

To investigate the impact of regression methods on resting‐state functional magnetic resonance imaging (rsfMRI). During rsfMRI preprocessing, regression analysis is considered effective for reducing the interference of physiological noise on the signal time course. However, it is unclear whether the regression method benefits rsfMRI analysis.