Comparison of convolutional-neural-networks-based method and LCModel on the quantification of in vivo magnetic resonance spectroscopy.

BACKGROUND: Quantification of metabolites concentrations in institutional unit (IU) is important for inter-subject and long-term comparisons in the applications of magnetic resonance spectroscopy (MRS). Recently, deep learning (DL) algorithms have found a variety of applications on the process of MRS data. A quantification strategy compatible to DL base MRS spectral processing method is, therefore, useful. MATERIALS AND METHODS: This study aims to investigate whether metabolite concentrations quantified using a convolutional neural network (CNN) based method, coupled with a scaling procedure that normalizes spectral signals for CNN input and linear regression, can effectively reflect variations in metabolite concentrations in IU across different brain regions with varying signal-to-noise ratios (SNR) and linewidths (LW). An error index based on standard error (SE) is proposed to indicate the confidence levels associated with metabolite predictions. In vivo MRS spectra were acquired from three brain regions of 43 subjects using a 3T system. RESULTS: The metabolite concentrations in IU of five major metabolites, quantified using CNN and LCModel, exhibit similar ranges with Pearson's correlation coefficients ranging from 0.24 to 0.78. The SE of the metabolites shows a positive correlation with Cramer-Rao lower bound (CRLB) (r=0.46) and  absolute CRLB (r=0.81), calculated by multiplying CRLBs with the quantified metabolite content. CONCLUSION: In conclusion, the CNN based method with the proposed scaling procedures can be employed to quantify in vivo MRS spectra and derive metabolites concentrations in IU. The SE can be used as error index, indicating predicted uncertainties for metabolites and sharing information similar to the absolute CRLB.

Brain plasticity of structural connectivity networks and topological properties in baseball players with different levels of expertise.

Brain plasticity in structural connectivity networks along the development of expertise has remained largely unknown. To address this, we recruited individuals with three different levels of baseball-playing experience: skilled batters (SB), intermediate batters (IB), and healthy controls (HC). We constructed their structural connectivity networks using diffusion tractography and compared their region-to-region structural connections and the topological characteristics of the constructed networks using graph-theoretical analysis. The group differences were detected in 35 connections predominantly involving sensorimotor and visual systems; the intergroup changes could be depicted either in a stepwise (HC < / = IB < / = SB) or a U-/inverted U-shaped manner as experience increased (IB < SB and/or HC, or opposite). All groups showed small-world topology in their constructed networks, but SB had increased global and local network efficiency than IB and/or HC. Furthermore, although the number and cortical regions identified as hubs of the networks in the three groups were highly similar, SB exhibited higher nodal global efficiency in both the dorsolateral and medial parts of the bilateral superior frontal gyri than IB. Our findings add new evidence of topological reorganization in brain networks associated with sensorimotor experience in sports. Interestingly, these changes do not necessarily increase as a function of experience as previously suggested in literature.

Study of Asian indexes by a newly derived dynamic model.

We take the stock prices as a dynamic system and characterize its movements by a newly derived dynamic model, called the new Price Reversion Model (nPRM), for which the solution is derived and carefully analyzed under different circumstances. We also develop a procedure of applying the nPRM to real daily closing prices of a stock index. This proposed procedure brings a different perspective to the study of stock prices based on thermodynamics, and the time varying coefficients in the nPRM offer economic meanings of the stock movements. More specifically, the average of smoothed historical data A in the nPRM, analogous to the environment temperature in the Newton's law of cooling, represent an implied equilibrium price. The heat transfer coefficient κ is adapted to be either negative or positive, which illustrates the speed of convergence or divergence of stock prices, respectively. The empirical study of ten Asian stock indexes shows that the nPRM accurately characterizes and forecasts the market values.

Pain sensitivity and the primary sensorimotor cortices: a multimodal neuroimaging study.

ABSTRACT: The primary somatosensory cortex (SI) is a critical part of the neural substrate underlying interindividual differences in pain sensitivity. Here, we investigated whether resting-state functional connectivity, gray matter density (GMD), and GABA and Glx (glutamate and glutamine) levels of the sensorimotor cortices were related to pain thresholds and whether such imaging measures could predict high and low pain sensitivity. Functional, structural, and spectroscopic magnetic resonance data were obtained from 48 healthy participants together with pain thresholds of the right index finger. Left and right sensorimotor networks (SMN) were extracted by means of independent component analysis, and GMD was measured within the combined SMN by means of voxel-based morphometry. Spectroscopic data were acquired from the bilateral sensorimotor cortices. Within the left SMN, functional connectivity to the right SI correlated positively with pain thresholds. In addition, GMD in the left SI and the GABA laterality index correlated positively with pain thresholds. A positive correlation was also found between the GABA laterality index and the left SMN connectivity to the right SI. Finally, the above mentioned functional connectivity and GMD measures could correctly predict high and low pain sensitivity in 83.7% of the study population. In summary, we showed that interindividual differences in pain sensitivity were related to the resting-state functional connectivity, interhemispheric GABA tone, and GMD of the sensorimotor cortices. Furthermore, high and low pain sensitivity could be predicted with high accuracy using imaging measures from the primary sensorimotor cortices.

Neurobiological changes in striatal glutamate are associated with trait impulsivity of differential reinforcement of low-rate-response behavior in male rats.

Impulsive action can be measured using rat's responses on a differential reinforcement of low-rate-response (DRL) task in which performance may be varied between rats. Nevertheless, neurobiological profiles underlying the trait impulsivity of DRL behavior remain largely unknown. Here, in vivo non-invasive proton magnetic resonance spectroscopy (1H-MRS) and Western blot assay were performed to assess neurobiological changes in the dorsal striatum (DS) and nucleus accumbens (NAc) in relation to individual differences in DRL behavior. A cohort of rats was subjected to acquire a DRL task over 14 daily sessions. High impulsive (HI) and low impulsive (LI) rats were screened by behavioral measures displaying a lower response efficiency and performing more nonreinforced responses in HI rats and vice versa. MRS measurements indicated that the HI group had a lower NAc glutamate (Glu) level than did the LI group, whereas no such difference was found in the other five metabolites in this area. Moreover, no intergroup difference was observed in any metabolite in the DS. The results of Western blot assay revealed that protein expressions of GluN1 (but not GluN2B) subunit of N-methyl-D-aspartate receptors in the DS and NAc were higher in the HI group than in the LI group. This inherent timing impulsivity was not attributed to risky behavioral propensity because both Hl and LI rats could acquire a risk-dependent choice. The findings of this study, supported by certain correlations among behavioral, brain imaging, and neuroreceptor indices, provide evidence of the neurobiological changes of striatal Glu underlying trait impulsive action of DRL behavior.

Brain metabolites in chronic migraine patients with medication overuse headache.

BACKGROUND: Medication overuse headache may be associated with widespread alterations along the thalamocortical pathway, a pathway involved in pain perception and disease progression. This study addressed whether brain metabolites in key regions of the thalamocortical pathway differed between chronic migraine patients with medication overuse headache and without medication overuse headache. METHODS: Magnetic resonance spectroscopic imaging was used to map metabolites in the bilateral anterior cingulate cortices, mid cingulate cortices, posterior cingulate cortices, and the thalami. Sixteen patients with medication overuse headache were compared with 16 matched patients without medication overuse headache and 16 matched healthy controls. RESULTS: Glutamate and glutamine in the right mid cingulate cortex and myo-inositol in the left anterior cingulate cortex were significantly higher in patients with medication overuse headache than patients without medication overuse headache, but similar to healthy controls. Both patient groups exhibited reduced N-acetyl-aspartate and creatine in the thalamus, reduced myo-inositol in the right anterior cingulate cortex, and elevated choline in the right mid cingulate cortex. Finally, a negative association between myo-inositol laterality index in the anterior cingulate cortices and number of days per month with acute medication use was found across all patients. CONCLUSIONS: Patients with medication overuse headache were characterized by a distinct concentration profile of myo-inositol, a glial marker, in the anterior cingulate cortices that may have arisen from medication overuse and could contribute to the development of medication overuse headache.

Left Ventricular Function and Myocardial Triglyceride Content on 3T Cardiac MR Predict Major Cardiovascular Adverse Events and Readmission in Patients Hospitalized with Acute Heart Failure.

BACKGROUND: This prospective study was designed to investigate whether myocardial triglyceride (TG) content from proton magnetic resonance spectroscopy (MRS) and left ventricular (LV) function parameters from cardiovascular magnetic resonance imaging (CMR) can serve as imaging biomarkers in predicting future major cardiovascular adverse events (MACE) and readmission in patients who had been hospitalized for acute heart failure (HF). METHODS: Patients who were discharged after hospitalization for acute HF were prospectively enrolled. On a 3.0 T MR scanner, myocardial TG contents were measured using MRS, and LV parameters (function and mass) were evaluated using cine. The occurrence of MACE and the HF-related readmission served as the endpoints. Independent predictors were identified using univariate and multivariable Cox proportional hazard regression analyses. RESULTS: A total of 133 patients (mean age, 52.4 years) were enrolled. The mean duration of follow-up in surviving patients was 775 days. Baseline LV functional parameters-including ejection fraction, LV end-diastolic volume, LV end-diastolic volume index (LVEDVI), and LV end-systolic volume (p < 0.0001 for all), and myocardial mass (p = 0.010)-were significantly associated with MACE. Multivariable analysis revealed that LVEDVI was the independent predictor for MACE, while myocardial mass was the independent predictor for 3- and 12-month readmission. Myocardial TG content (lipid resonances δ 1.6 ppm) was significantly associated with readmission in patients with ischemic heart disease. CONCLUSIONS: LVEDVI and myocardial mass are potential imaging biomarkers that independently predict MACE and readmission, respectively, in patients discharged after hospitalization for acute HF. Myocardial TG predicts readmission in patients with a history of ischemic heart disease.

Reduction of lipid contamination in MR spectroscopy imaging using signal space projection.

PURPOSE: Lipid contamination can complicate the metabolite quantification in MR spectroscopic imaging (MRSI). In addition to various experimental methods demonstrated to be feasible for lipid suppression, the postprocessing method is beneficial in the flexibility of applications. In this study, the signal space projection (SSP) algorithm is proposed to suppress the lipid signal in the MRSI. METHODS: The performance of lipid suppression using SSP and SSP combined with the Papoulis-Gerchberg (PG) algorithm (PG+SSP) is examined in 2D MRSI data and the results were compared with outer volume saturation (OVS) methods. Up to 10 lipid spatial components were extracted by SSP from lipid signals in the range of 0.8~1.5 ppm. RESULTS: Our results show that most lipid signals were found in the first 4 to 5 components and that lipid signals on the spectra can be suppressed using 4 to 5 components. Metabolites concentrations were quantified using LCModel. Two regions of interest (ROIs) were manually selected on the peripheral and inner brain regions. The quantification of metabolites in terms of fitting reliability (CRLB) and spatial variations within ROIs (SpaVar) is improved using SSP. When 5 to 6 components were used in SSP and PG+SSP, the metabolite concentrations and the associated SpaVar and CRLB are at the same level as those from the OVS. CONCLUSION: We have demonstrated that the SSP method can be used to suppress the lipid signals of MRSI and SSP with 5 to 6 components is suggested to have a similar suppression performance as the OVS method.

Reproducibility of structural brain connectivity and network metrics using probabilistic diffusion tractography.

The structural connectivity network constructed using probabilistic diffusion tractography can be characterized by the network metrics. In this study, short-term test-retest reproducibility of structural networks and network metrics were evaluated on 30 subjects in terms of within- and between-subject coefficient of variance (CVws, CVbs), and intra class coefficient (ICC) using various connectivity thresholds. The short-term reproducibility under various connectivity thresholds were also investigated when subject groups have same or different sparsity. In summary, connectivity threshold of 0.01 can exclude around 80% of the edges with CVws = 73.2 ± 37.7%, CVbs = 119.3 ± 44.0% and ICC = 0.62 ± 0.19. The rest 20% edges have CVws < 45%, CVbs < 90%, ICC = 0.75 ± 0.12. The presence of 1% difference in the sparsity can cause additional within-subject variations on network metrics. In conclusion, applying connectivity thresholds on structural network to exclude spurious connections for the network analysis should be considered as necessities. Our findings suggest that a connectivity threshold over 0.01 can be applied without significant effect on the short-term when network metrics are evaluated at the same sparsity in subject group. When the sparsity is not the same, the procedure of integration over various connectivity thresholds can provide reliable estimation of network metrics.

Relative latency and temporal variability of hemodynamic responses at the human primary visual cortex.

The blood-oxygen-level-dependent (BOLD) functional MRI (fMRI) signal is a robust surrogate for local neuronal activity. However, it has been shown to vary substantially across subjects, brain regions, and repetitive measurements. This variability represents a limit to the precision of the BOLD response and the ability to reliably discriminate brain hemodynamic responses elicited by external stimuli or behavior that are nearby in time. While the temporal variability of the BOLD signal at human visual cortex has been found in the range of a few hundreds of milliseconds, the spatial distributions of the average and standard deviation of this temporal variability have not been quantitatively characterized. Here we use fMRI measurements with a high sampling rate (10Hz) to map the latency, intra- and inter-subject variability of the evoked BOLD signal in human primary (V1) visual cortices using an event-related fMRI paradigm. The latency relative to the average BOLD signal evoked by 30 stimuli was estimated to be 0.03±0.20s. Within V1, the absolute value of the relative BOLD latency was found correlated to intra- and inter-subject temporal variability. After comparing these measures to retinotopic maps, we found that locations with V1 areas sensitive to smaller eccentricity have later responses and smaller inter-subject variabilities. These correlations were found from data with either short inter-stimulus interval (ISI; average 4s) or long ISI (average 30s). Maps of the relative latency as well as inter-/intra-subject variability were found visually asymmetric between hemispheres. Our results suggest that the latency and variability of regional BOLD signal measured with high spatiotemporal resolution may be used to detect regional differences in hemodynamics to inform fMRI studies. However, the physiological origins of timing index distributions and their hemispheric asymmetry remain to be investigated.

Developing and validating a multivariable prediction model to improve the diagnostic accuracy in determination of cervical versus endometrial origin of uterine adenocarcinomas: A prospective MR study combining diffusion-weighted imaging and spectroscopy.

BACKGROUND: A triage test to assist clinical decision-making on choosing primary chemoradiation for cervical carcinomas or primary surgery for endometrial carcinomas is important. PURPOSE OR HYPOTHESIS: To develop and validate a multiparametric prediction model based on MR imaging and spectroscopy in distinguishing adenocarcinomas of uterine cervical or endometrial origin. STUDY TYPE: Prospective diagnostic accuracy study. POPULATION: Eighty-seven women: 25 cervical and 62 endometrial adenocarcinomas divided into training (n = 43; cervical/endometrial adenocarcinomas = 11/32) and validation (n = 44; 14/30) datasets. FIELD STRENGTH/SEQUENCE: The 3T diffusion-weighted (DW) MR imaging and MR spectroscopy. ASSESSMENT: Morphology, volumetric DW MR imaging and spectroscopy (MDS) scoring system with total points 0-5, based on presence of the following MR features assessed independently by two radiologists: (a) epicenter at the cervix, (b) rim enhancement, (c) disrupted cervical stromal integrity, (d) mean volumetric apparent diffusion coefficient values (ADCmean) higher than 0.98 × 10-3 mm2 /s, (e) fatty acyl δ 1.3 ppm more than 161.92 mM. Histopathology as gold standard. STATISTICAL TESTS: Logistic regression and receiver operator characteristic (ROC) curves analysis. RESULTS: For both the training and validation datasets, the MDS score achieved an accuracy of 93.0% and 84.1%, significantly higher than that of morphology (88.4% and 79.5%), ADC value (74.4% and 68.2%), and spectroscopy (81.4% and 68.2%; P < 0.05 for all). The performances of the scoring were superior to the morphology in the training dataset (areas under the receiver operating characteristics curve [AUC] = 0.95 vs. 0.89; P = 0.046), but not in the validation dataset (AUC = 0.90 vs. 0.85; P = 0.289). DATA CONCLUSION: MDS score has potentials to improve distinguishing adenocarcinomas of cervical or endometrial origin, and warrants large-scale studies for further validation. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1654-1666.

Neurochemical changes in the medial wall of the brain in chronic migraine.

Migraine chronification is associated with a dysfunctional thalamocortical pathway. The present study addressed whether abnormal concentrations of neurochemicals exist in key brain regions of this pathway in chronic migraine. Magnetic resonance spectroscopic imaging of the bilateral medial walls of the brain was used to measure choline, creatine, glutamate and glutamine, myo-inositol, and N-acetyl-aspartate in chronic migraine patients and in matched groups of episodic migraine patients and healthy controls. A region of interest analysis was conducted to examine whether N-acetyl-aspartate, a marker of neuronal integrity, was reduced in the thalamus, occipital cortex and anterior cingulate cortex in chronic migraine. Interregional N-acetyl-aspartate correlations among these regions of interest were also examined. Additionally, statistical mapping was performed for all the metabolites throughout the medial walls. Chronic migraine was associated with N-acetyl-aspartate reductions in the bilateral thalami and in the right anterior cingulate. The N-acetyl-aspartate reduction in the right thalamus correlated with disease duration. Compared with healthy controls, patients with chronic migraine had altered interregional N-acetyl-aspartate correlations between the right thalamus-anterior cingulate and thalamus-occipital cortex, and between the left and right anterior cingulate. N-acetyl-aspartate concentrations and interregional correlations in patients with episodic migraine were between those of healthy controls and chronic migraine patients. The unconstrained analyses revealed a reduction of myo-inositol in the left anterior and posterior cingulate in both patient groups as well as a negative association with depression scores for the anterior cingulate in the combined patient group. In addition, migraine patients with headache on the scan day (irrespective of diagnosis) had reduced N-acetyl-aspartate and total creatine concentrations in the right dorsal anterior cingulate. Reduced N-acetyl-aspartate metabolism and altered interregional N-acetyl-aspartate correlations lend support to the role of thalamocortical dysfunction in migraine chronification. It remains to be established if the pattern of changes within the N-acetyl-aspartate network is specific to chronic migraine or can be found in other chronic pain conditions.

Simultaneous multi-slice inverse imaging of the human brain.

Ultrafast functional magnetic resonance imaging (fMRI) can measure blood oxygen level dependent (BOLD) signals with high sensitivity and specificity. Here we propose a novel method: simultaneous multi-slice inverse imaging (SMS-InI) - a combination of simultaneous multi-slice excitation, simultaneous echo refocusing (SER), blipped controlled aliasing in parallel imaging echo-planar imaging (EPI), and regularized image reconstruction. Using a 32-channel head coil array on a 3 T scanner, SMS-InI achieves nominal isotropic 5-mm spatial resolution and 10 Hz sampling rate at the whole-brain level. Compared with traditional inverse imaging, we found that SMS-InI has higher spatial resolution with lower signal leakage and higher time-domain signal-to-noise ratio with the optimized regularization parameter in the reconstruction. SMS-InI achieved higher effective resolution and higher detection power in detecting visual cortex activity than InI. SMS-InI also detected subcortical fMRI signals with the similar sensitivity and localization accuracy like EPI. The spatiotemporal resolution of SMS-InI was used to reveal that presenting visual stimuli with 0.2 s latency between left and right visual hemifield led to 0.2 s relative hemodynamic response latency between the left and right visual cortices. Together, these results indicate that SMS-InI is a useful tool in measuring cortical and subcortical hemodynamic responses with high spatiotemporal resolution.

Resting GABA concentration predicts inhibitory control during an auditory Go-Nogo task.

Inhibitory control plays an important role in goal-directed behavior. Although substantial inter-individual variability exists in the behavioral performance of response inhibition, the corresponding modulating neurochemical and neurophysiological mechanisms remain unclear. Thus, the present study aimed to explore the relationship between behavioral response inhibition, GABA+ concentrations and automatic sensory gating (SG) in the auditory cortices. We recruited 19 healthy adults to undergo magnetoencephalography, magnetic resonance spectroscopy (MRS), and behavioral experiments. A paired-stimulus paradigm was used to study SG of the auditory cortices, and an auditory-driven Go-Nogo task was used to evaluate the behavioral response inhibition. Resting GABA+ concentrations were measured in the bilateral superior temporal gyri by means of MRS. Neither GABA+ concentrations nor auditory SG showed significant hemispheric asymmetry. However, an enhanced SG (lower ratio) was found to correlate with improved behavioral inhibition. Moreover, a higher GABA+ concentration was strongly related to improved inhibitory control. These findings highlight the important role of automatic neurophysiological processes and inhibitory neurotransmitters in the prediction of the behavioral performance of inhibitory control.

Automatic inhibitory function in the human somatosensory and motor cortices: An MEG-MRS study.

While the automatic inhibitory function of the human cerebral cortex has been extensively investigated by means of electrophysiological recordings, the corresponding modulating neurochemical mechanisms remain unclear. We aimed to examine whether the primary somatosensory (SI) and primary motor cortical (MI) inhibitory function is associated with endogenous GABA levels. Eighteen young participants received paired-pulse and single-pulse electrical stimulation to the median nerve during magnetoencephalographic recordings. The SI sensory gating (SG), considered as an automatic inhibitory ability, was measured as the amplitude ratio of Stimulus 2 over Stimulus 1, in the paired-pulse paradigm. In addition, stimulus-induced beta activity, considered to originate from MI and also to be related to inhibitory function, was estimated using the single-pulse paradigm. The GABA+ concentration of the sensorimotor cortex was acquired from each subject by using magnetic resonance spectroscopy (MRS). A lower SG ratio in SI was significantly associated with an increased beta power in MI. More importantly, the beta rebound power, but not SI SG ratio, was positively correlated with GABA+ concentration. Our findings show a tight functional relationship between SI and MI during processing of automatic inhibition. GABA+ levels appear to be more closely related to the automatic inhibitory function of MI than SI.

Predictive value of 1H MR spectroscopy and 18F-FDG PET/CT for local control of advanced oropharyngeal and hypopharyngeal squamous cell carcinoma receiving chemoradiotherapy: a prospective study.

PURPOSE: To determine whether pretreatment in vivo 1H magnetic resonance (MR) spectroscopy at 3 Tesla (T) and 18F-FDG PET/CT can offer predictive power regarding the local control of oropharyngeal or hypopharyngeal squamous cell carcinoma (OHSCC) patients. MATERIALS AND METHODS: 1H MR spectroscopy was performed in addition to conventional MR imaging before definitive chemoradiotherapy in 58 patients with advanced OHSCC. The relationship of local control with the 1H MR spectroscopy and 18F-FDG PET/CT parameters was analyzed. RESULTS: With a median follow-up of 17.6 months, 13 (22.4%) patients exhibited local failure; whereas the remaining 45 achieved local control. Kaplan-Meier analysis identified age > 60 years, creatine level on MRS ≦ 6.02 mM, glutamine and glutamate (Glx) level on MRS > 3.31 mM, and total lesion glycolysis (TLG) on 18F-FDG PET/CT > 217.18 g/mL × mL as significant adverse predictors for 2-year local control. Multivariate Cox regression analysis showed that age (p=0.017), Glx level on MRS (p=0.021), and TLG on 18F-FDG PET/CT (p=0.028) retained their independent prognostic significance. A scoring system was constructed based on the sum of these three factors. We found that patients with scores of 2-3 had significantly poorer local control rates than patients with scores of 0-1 (33.3% versus 86.8%, p=0.003). CONCLUSION: We conclude that Glx on 1H MR spectroscopy at 3 T was the independent prognostic factor for local control of OHSCC patients treated with chemoradiotherapy, and its combination with age and TLG may help identify a subgroup of patients at high risk for developing local failure.

1 H MR spectroscopy in cervical carcinoma using external phase array body coil at 3.0 Tesla: Prediction of poor prognostic human papillomavirus genotypes.

PURPOSE: To assess the clinical value of proton (1 H) MR spectroscopy in cervical carcinomas, in the prediction of poor prognostic human papillomavirus (HPV) genotypes as well as persistent disease following concurrent chemoradiotherapy (CCRT). MATERIALS AND METHODS: 1 H MR spectroscopy using external phase array coil was performed in 52 consecutive cervical cancer patients at 3 Tesla (T). Poor prognostic HPV genotypes (alpha-7 species or absence of HPV infection) and persistent cervical carcinoma after CCRT were recorded. Statistical significance was calculated with the Mann-Whitney two-sided nonparametric test and areas under the receiver operating characteristics curve (AUC) analysis. RESULTS: A 4.3-fold (P = 0.032) increased level of methyl resonance at 0.9 ppm was found in the poor prognostic HPV genotypes, mainly attributed to the presence of HPV18, with a sensitivity of 75%, a specificity of 81%, and an AUC of 0.76. Poor prognostic HPV genotypes were more frequently observed in patients with adeno-/adenosquamous carcinoma (Chi-square, P < 0.0001). In prediction of the four patients with persistent disease after CCRT, elevated methyl resonance demonstrated a sensitivity of 100%, a specificity of 74%, and an AUC of 0.82. CONCLUSION: 1 H MR spectroscopy at 3T can be used to depict the elevated lipid resonance levels in cervical carcinomas, as well as help to predict the poor prognostic HPV genotypes and persistent disease following CCRT. Further large studies with longer follow up times are warranted to validate our initial findings. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:899-907.

Simultaneous detection of valine and lactate using MEGA-PRESS editing in pyogenic brain abscess.

Valine and lactate have been recognized as important metabolic markers to diagnose brain abscess by means of MRS. However, in vivo unambiguous detection and quantification is hampered by macromolecular contamination. In this work, MEGA-PRESS difference editing of valine and lactate is proposed. The method is validated in vitro and applied for quantitative in vivo experiments in one healthy subject and two brain abscess patients. It is demonstrated that with this technique the overlapping lipid signal can be reduced by more than an order of magnitude and thus the robustness of valine and lactate detection in vivo can be enhanced. Quantification of the two abscess MEGA-PRESS spectra yielded valine/lactate concentration ratios of 0.10 and 0.27. These ratios agreed with the concentration ratios determined from concomitantly acquired short-TE PRESS data and were in line with literature values. The quantification accuracy of lactate (as measured with Cramér-Rao lower bounds in LCModel processing) was better for MEGA-PRESS than for short-TE PRESS in all acquired in vivo datasets. The Cramér-Rao lower bounds of valine were only better for MEGA-PRESS in one of the two abscess cases, while in the other case coediting of isoleucine confounded the quantification in the MEGA-PRESS analysis. MEGA-PRESS and short-TE PRESS should be combined for unambiguous quantification of amino acids in abscess measurements. Simultaneous valine/lactate MEGA-PRESS editing might benefit the distinction of brain abscesses from tumors, and further categorization of bacteria with reasonable sensitivity and specificity.

Identification of plant vacuolar transporters mediating phosphate storage.

Plant vacuoles serve as the primary intracellular compartments for inorganic phosphate (Pi) storage. Passage of Pi across vacuolar membranes plays a critical role in buffering the cytoplasmic Pi level against fluctuations of external Pi and metabolic activities. Here we demonstrate that the SPX-MFS proteins, designated as PHOSPHATE TRANSPORTER 5 family (PHT5), also named Vacuolar Phosphate Transporter (VPT), function as vacuolar Pi transporters. Based on (31)P-magnetic resonance spectroscopy analysis, Arabidopsis pht5;1 loss-of-function mutants accumulate less Pi and exhibit a lower vacuolar-to-cytoplasmic Pi ratio than controls. Conversely, overexpression of PHT5 leads to massive Pi sequestration into vacuoles and altered regulation of Pi starvation-responsive genes. Furthermore, we show that heterologous expression of the rice homologue OsSPX-MFS1 mediates Pi influx to yeast vacuoles. Our findings show that a group of Pi transporters in vacuolar membranes regulate cytoplasmic Pi homeostasis and are required for fitness and plant growth.

Effects of Frequency Drift on the Quantification of Gamma-Aminobutyric Acid Using MEGA-PRESS.

The MEGA-PRESS method is the most common method used to measure γ-aminobutyric acid (GABA) in the brain at 3T. It has been shown that the underestimation of the GABA signal due to B0 drift up to 1.22 Hz/min can be reduced by post-frequency alignment. In this study, we show that the underestimation of GABA can still occur even with post frequency alignment when the B0 drift is up to 3.93 Hz/min. The underestimation can be reduced by applying a frequency shift threshold. A total of 23 subjects were scanned twice to assess the short-term reproducibility, and 14 of them were scanned again after 2-8 weeks to evaluate the long-term reproducibility. A linear regression analysis of the quantified GABA versus the frequency shift showed a negative correlation (P < 0.01). Underestimation of the GABA signal was found. When a frequency shift threshold of 0.125 ppm (15.5 Hz or 1.79 Hz/min) was applied, the linear regression showed no statistically significant difference (P > 0.05). Therefore, a frequency shift threshold at 0.125 ppm (15.5 Hz) can be used to reduce underestimation during GABA quantification. For data with a B0 drift up to 3.93 Hz/min, the coefficients of variance of short-term and long-term reproducibility for the GABA quantification were less than 10% when the frequency threshold was applied.