Tsuyoshi Matsuda

Negative correlation between brain glutathione level and negative symptoms in schizophrenia: A 3T 1H-MRS study

Background Glutathione (GSH), a major intracellular antioxidant, plays a role in NMDA receptor-mediated neurotransmission, which is involved in the pathophysiology of schizophrenia. In the present study, we aimed to investigate whether GSH levels are altered in the posterior medial frontal cortex of schizophrenic patients. Furthermore, we examined correlations between GSH levels and clinical variables in patients. Methods and Findings Twenty schizophrenia patients and 16 age- and gender-matched normal controls were enrolled to examine the levels of GSH in the posterior medial frontal cortex by using 3T SIGNA EXCITE 1H-MRS with the spectral editing technique, MEGA-PRESS. Clinical variables of patients were assessed by the Global Assessment of Functioning (GAF), Scale for the Assessment of Negative Symptoms (SANS), Brief Psychiatric Rating Scale (BPRS), Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS), and five cognitive performance tests (Word Fluency Test, Stroop Test, Trail Making Test, Wisconsin Card Sorting Test and Digit Span Distractibility Test). Levels of GSH in the posterior medial frontal cortex of schizophrenic patients were not different from those of normal controls. However, we found a significant negative correlation between GSH levels and the severity of negative symptoms (SANS total score and negative symptom subscore on BPRS) in patients. There were no correlations between brain GSH levels and scores on any cognitive performance test except Trail Making Test part A. Conclusion These results suggest that GSH levels in the posterior medial frontal cortex may be related to negative symptoms in schizophrenic patients. Therefore, agents that increase GSH levels in the brain could be potential therapeutic drugs for negative symptoms in schizophrenia.

Measurement of variation in the human cerebral GABA level by in vivo MEGA-editing proton MR spectroscopy using a clinical 3 T instrument and its dependence on brain region and the female menstrual cycle.

The objectives of this study were to examine the reproducibility of the MEGA‐editing J‐difference technique and to determine the normal variation in the γ‐aminobutyric acid (GABA) level depending on the cerebral region and its fluctuation according to the menstrual cycle as baseline data for clinical application. The participants consisted of 15 normal adult volunteers (eight men and seven women), and all measurements were repeated twice in all participants. The MEGA‐editing pulses were incorporated into point‐resolved spectroscopy on a 3 T instrument to obtain the J‐difference editing spectra from a voxel located in the lentiform nuclei (LN), left frontal lobe (FL), and anterior cingulate cortex (AC). The GABA levels in the gray matter (GM) were compensated by the fraction ratios of the gray and white matters and cerebrospinal fluid in the measurement volume. The extent of the variation in GABA was almost the same as that observed in the major metabolites, and its reproducibility was also maintained (intraclass correlation coefficient > 0.7). GABA level was highest in LN and lowest in AC. A difference in the GABA level between the follicular and luteal phases of the menstrual cycle was found in both LN and FL, but not in AC. This technique showed the differences in the GABA levels in the GM and the region‐specific decrease in the GABA levels during the womens luteal phase. Hum Brain Mapp, 2011.

Ischemic Findings of T2*-Weighted 3-Tesla MRI in Acute Stroke Patients

Background: We compared ischemic findings on gradient echo-type T2*-weighted images at 3-tesla MRI (T2*WI) in patients with acute ischemia and major vessel occlusion, and stroke patients with lacunar infarction or branch atheromatous disease. Methods: Our study population consisted of 45 patients with acute stroke. They underwent 3-tesla MRI within 12 h of stroke onset. Included were 24 patients (13 men and 11 women, mean age 68 years) with major vessel occlusion and 21 patients (11 men and 10 women, mean age 69 years) with minor infarction such as lacunar infarcts or branch atheromatous disease. We classified vascular ischemic findings of T2*WI into 3 sign categories, i.e. artery susceptibility sign, cortical vessel sign (hypointensity and enlargement of the cortical vessels) and brush sign (hypointensity of vessels in the deep white matter). Decreased intensity in the ischemic parenchyma was designated ischemic tissue sign. We compared regions of interest in the hypoperfused area on flow-sensitive alternating inversion recovery (FAIR) images with our vascular ischemic findings. Results: None of the vascular ischemic signs nor the ischemic tissue sign were found in patients with minor vessel disease. All 24 patients with major vessel occlusion manifested the cortical vessel sign, 23 the brush sign. The area with ischemic vessel signs on T2*WI was almost as large or somewhat smaller than the hypoperfused area on FAIR images. Compared to the contralateral side, 14 of 24 patients (58.3%) with major vessel occlusion showed decreased intensity in the ischemic parenchyma (ischemic tissue sign). Region of interest measurements on FAIR images demonstrated greater hypoperfusion in the area classified as ischemic tissue sign on T2*WI. Conclusions: Ischemic vessel signs and the ischemic tissue sign on T2*WI at 3 T would be useful to evaluate the extensive ischemia due to major vessel occlusion and may be correlated with the blood-oxygen-level-dependent effect due to increased deoxyhemoglobin. The ischemic tissue sign may be reflective of severe ischemia.

Influence of work shift on glutamic acid and gamma-aminobutyric acid (GABA): Evaluation with proton magnetic resonance spectroscopy at 3T

Working conditions such as shift work constitute a well-known risk factor for insomnia and excessive daytime sleepiness complaints. We compared brain gamma-aminobutyric acid (GABA), glutamic acid (Glu), glutamine (Gln), and Glx (Glu+Gln) levels in day-shift versus alternate-shift workers with proton magnetic resonance spectroscopy ((1)H-MRS) at 3T. The study population consisted of 32 healthy adult volunteers (16 day-shift and 16 alternate-shift workers). Each subject underwent MRS conducted using a MEGA-PRESS sequence in the early morning and early evening on the same day. Spectroscopy voxels (3.0 cm × 3.0 cm × 3.0 cm) were placed in the frontal lobe and parieto-occipital lobe. The GABA/Cr ratio in the frontal lobe was significantly lower for the alternate-shift group than for the day-shift group in the early evening (1.885 vs. 0.875). For the other metabolite ratios (Gln/Cr and Glx/Cr), there were no significant differences between the two groups regardless of morning or evening schedule. Our preliminary finding represents a possible alteration of GABA content in the brain related to an irregular work schedule.

Comparison of FAIR technique with different inversion times and post contrast dynamic perfusion MRI in chronic occlusive cerebrovascular disease

The purpose of this study was to examine the signal change occurring with different inversion times (TIs) of the flow-sensitive alternating inversion recovery (FAIR) technique and to compare with the perfusion image obtained with Gd-DTPA injection. The subjects were 11 patients with unilateral occlusive cerebrovascular disease. Two FAIR images with different TIs (800 ms and 1600 ms) were measured for each patient and dynamic perfusion MRI was performed to produce four kinds of parameter maps: mean transit time (MTT), time to peak (TTP), relative cerebral blood flow (rCBF) and relative cerebral blood volume (rCBV) maps. Asymmetry ratios (ARs) between the affected and contra-lateral vascular sides were measured in both FAIR images and the four dynamic parameter maps. The AR of the MTT map of the four parameters showed the highest correlation with that of the FAIR images, especially with that of TI = 1600 ms (r = 0.829), and the AR of the rCBV map revealed the worst correlation with the FAIR images. The AR of the FAIR image with TI = 800 ms was less correlated with that of MTT than that with TI = 1600 ms. These results suggested that the signal intensity of the FAIR image was influenced by flow transition time and the change in TI could be used to select the flow with a different transition time. Our study suggested that a longer TI in the FAIR technique might be more useful than a shorter TI for evaluating chronic occlusive cerebrovascular disease in the clinical setting.

Quantitative analysis of hepatic fat fraction by single-breath-holding MR spectroscopy with T 2 correction: phantom and clinical study with histologic assessment

The focus of this study was on the investigation of the accuracy of the fat fraction of the liver by use of single-breath-holding magnetic resonance spectroscopy (MRS) with T2 correction. Single-voxel proton MRS was performed with several TE values, and the fat fraction was determined with and without T2 correction. MRS was also performed with use of the point-resolved spectroscopy sequence in single breath holding. The T2 values of both water and fat were determined separately at the same time, and the effect of T2 on the fat fraction was corrected. In addition, MRS-based fat fractions were compared with the degree of hepatic steatosis (HS) by liver biopsy in human subjects. With T2 correction, the MRI-derived fat fractions were in good agreement with the fat fractions in all phantoms, but the fat fractions were overestimated without T2 correction. R2 values were in good agreement with the preset iron concentrations in the phantoms. The MRI-derived fat fraction was well correlated with the degree of HS. Iron deposited in the liver affects the signal strength when proton MRS is used for detection of the fat signal in the liver. However, the fat signal can be evaluated more accurately when the T2 correction is applied. Breath-holding MRS minimizes the respiratory motion, and it can be more accurate in the quantification of the hepatic fat fraction.

High gamma-aminobutyric acid level in cortical tubers in epileptic infants with tuberous sclerosis complex measured with the MEGA-editing J-difference method and a three-Tesla clinical MRI Instrument

The purpose of this study was to estimate the gamma-aminobutyric acid (GABA) and glutamate plus glutamine (Glx) concentrations in the cortical tubers of patients with tuberous sclerosis complex (TSC) using the MEGA-editing J-difference method and a stimulated echo-acquisition mode with a short echo time, and to determine which abnormality was more dominant between GABA and Glx in patients with TSC with epilepsy. This study included six patients with TSC (mean age, 4.3 years) and seven control subjects (mean age, 4.8 years). Measurements were obtained with a three-Tesla apparatus and postprocessing was conducted with an LCModel. The GABA level in the cortical gray matter (cgGABA) was calculated as a result of segmentation in voxels and from the literature values for gray and white matter ratios for GABA. Increased GABA and myo-inositol (mI) concentrations and a decreased N-acetyl aspartate (NAA) concentration were observed in the cortical tubers. The cgGABA level, and cgGABA/NAA and cgGABA/Glx ratios were also higher in patients with TSC than in control subjects. No significant difference was found in Glx concentration between patients with TSC and control subjects. Although the number of patients with TSC in this study was small, the increase in GABA and no significant change in Glx were consistent with previous neurochemical studies and support the hypothesis that brain GABA plays a key role in the pathophysiology of epilepsy during the process of neuronal development.

Arterial Transit Time Mapping Obtained by Pulsed Continuous 3D ASL Imaging with Multiple Post-Label Delay Acquisitions: Comparative Study with PET-CBF in Patients with Chronic Occlusive Cerebrovascular Disease

Arterial transit time (ATT) is most crucial for measuring absolute cerebral blood flow (CBF) by arterial spin labeling (ASL), a noninvasive magnetic resonance (MR) perfusion assessment technique, in patients with chronic occlusive cerebrovascular disease. We validated ASL-CBF and ASL-ATT maps calculated by pulsed continuous ASL (pCASL) with multiple post-label delay acquisitions in patients with occlusive cerebrovascular disease. Fifteen patients underwent MR scans, including pCASL, and positron emission tomography (PET) scans with 15O-water to obtain PET-CBF. MR acquisitions with different post-label delays (1.0, 1.5, 2.0, 2.5 and 3.0 sec) were also obtained for ATT correction. The theoretical framework of 2-compartmental model (2CM) was also used for the delay compensation. ASL-CBF and ASL-ATT were calculated based on the proposed 2CM, and the effect on the CBF values and the ATT correction characteristics were discussed. Linear regression analyses were performed both on pixel-by-pixel and region-of-interest bases in the middle cerebral artery (MCA) territory. There were significant correlations between ASL-CBF and PET-CBF both for voxel values (r = 0.74 ± 0.08, slope: 0.87 ± 0.22, intercept: 6.1 ± 4.9) and for the MCA territorial comparison in both affected (R2 = 0.67, y = 0.83x + 6.3) and contralateral sides (R2 = 0.66, y = 0.74x + 6.3). ASL-ATTs in the affected side were significantly longer than those in the contralateral side (1.51 ± 0.41 sec and 1.12 ± 0.30 sec, respectively, p <0.0005). CBF measurement using pCASL with delay compensation was feasible and fairly accurate even in altered hemodynamic states.

Validation of band counts in eyestalks for the determination of age of Antarctic krill, Euphausia superba

Using known-age Antarctic krill (Euphausia superba) grown from eggs hatched at two different laboratories, we validate the annual pattern of bands deposited in the eyestalks of krill and determine the absolute age of these animals. Ages two through five years were validated, and these animals ranged from 37.1 to 62.6 mm in total length. The band counts in these individuals were either identical to their absolute ages, or only failed to agree by a few months, which demonstrates the accuracy of this method. Precision and bias were estimated graphically using Chang’s index (Coefficient of Variation = 5.03%). High accuracy and precision between readers and low ageing bias indicate that longitudinal sections of eyestalks can be used to age krill in wild samples and to develop age-based stock assessment models for krill. Archival samples preserved in formalin (5%) and stored in ambient conditions were also readable. Ageing preserved krill will provide the opportunity to examine changes in growth among krill populations within the Southern Ocean and to retrospectively examine changes in krill production over the last century to better understand the historical and future impacts of climate change on this critical Southern Ocean species.

Arterial Transit Time-corrected Renal Blood Flow Measurement with Pulsed Continuous Arterial Spin Labeling MR Imaging

Purpose: The importance of arterial transit time (ATT) correction for arterial spin labeling MRI has been well debated in neuroimaging, but it has not been well evaluated in renal imaging. The purpose of this study was to evaluate the feasibility of pulsed continuous arterial spin labeling (pcASL) MRI with multiple post-labeling delay (PLD) acquisition for measuring ATT-corrected renal blood flow (ATC-RBF). Materials and Methods: A total of 14 volunteers were categorized into younger (n = 8; mean age, 27.0 years) and older groups (n = 6; 64.8 years). Images of pcASL were obtained at three different PLDs (0.5, 1.0, and 1.5 s), and ATC-RBF and ATT were calculated using a single-compartment model. To validate ATC-RBF, a comparative study of effective renal plasma flow (ERPF) measured by 99mTc-MAG3 scintigraphy was performed. ATC-RBF was corrected by kidney volume (ATC-cRBF) for comparison with ERPF. Results: The younger group showed significantly higher ATC-RBF (157.68 ± 38.37 mL/min/100 g) and shorter ATT (961.33 ± 260.87 ms) than the older group (117.42 ± 24.03 mL/min/100 g and 1227.94 ± 226.51 ms, respectively; P < 0.05). A significant correlation was evident between ATC-cRBF and ERPF (P < 0.05, r = 0.47). With suboptimal single PLD (1.5 s) settings, there was no significant correlation between ERPF and kidney volume-corrected RBF calculated from single PLD data. Conclusion: Calculation of ATT and ATC-RBF by pcASL with multiple PLD was feasible in healthy volunteers, and differences in ATT and ATC-RBF were seen between the younger and older groups. Although ATT correction by multiple PLD acquisitions may not always be necessary for RBF quantification in the healthy subjects, the effect of ATT should be taken into account in renal ASL–MRI as debated in brain imaging.