Optimization of the flip angles of narrow-band editing pulses in J-difference edited MRS of lactate at 3T.

PURPOSE: Application of highly selective editing RF pulses provides a means of minimizing co-editing of contaminants in J-difference MRS (MEGA), but it causes reduction in editing yield. We examined the flip angles (FAs) of narrow-band editing pulses to maximize the lactate edited signal with minimal co-editing of threonine. METHODS: The effect of editing-pulse FA on the editing performance was examined, with numerical and phantom analyses, for bandwidths of 17.6-300 Hz in MEGA-PRESS editing of lactate at 3T. The FA and envelope of 46 ms Gaussian editing pulses were tailored to maximize the lactate edited signal at 1.3 ppm and minimize co-editing of threonine. The optimized editing-pulse FA MEGA scheme was tested in brain tumor patients. RESULTS: Simulation and phantom data indicated that the optimum FA of MEGA editing pulses is progressively larger than 180° as the editing-pulse bandwidth decreases. For 46 ms long 17.6 Hz bandwidth Gaussian pulses and other given sequence parameters, the lactate edited signal was maximum at the first and second editing-pulse FAs of 241° and 249°, respectively. The edit-on and difference-edited lactate peak areas of the optimized FA MEGA were greater by 43% and 25% compared to the 180°-FA MEGA, respectively. In-vivo data confirmed the simulation and phantom results. The lesions of the brain tumor patients showed elevated lactate and physiological levels of threonine. CONCLUSION: The lactate MEGA editing yield is significantly increased with editing-pulse FA much larger than 180° when the editing-pulse bandwidth is comparable to the lactate quartet frequency width.

J-Difference editing (MEGA) of lactate in the human brain at 3T.

PURPOSE: The need to detect and quantify brain lactate accurately by MRS has stimulated the development of editing sequences based on J coupling effects. In J-difference editing of lactate, threonine can be co-edited and it contaminates lactate estimates due to the spectral proximity of the coupling partners of their methyl protons. We therefore implemented narrow-band editing 180° pulses (E180) in MEGA-PRESS acquisitions to resolve separately the 1.3-ppm resonances of lactate and threonine. METHODS: Two 45.3-ms rectangular E180 pulses, which had negligible effects 0.15-ppm away from the carrier frequency, were implemented in a MEGA-PRESS sequence with TE 139 ms. Three acquisitions were designed to selectively edit lactate and threonine, in which the E180 pulses were tuned to 4.1 ppm, 4.25 ppm, and a frequency far off resonance. Editing performance was validated with numerical analyses and acquisitions from phantoms. The narrow-band E180 MEGA and another MEGA-PRESS sequence with broad-band E180 pulses were evaluated in six healthy subjects. RESULTS: The 45.3-ms E180 MEGA offered a difference-edited lactate signal with lower intensity and reduced contamination from threonine compared to the broad-band E180 MEGA. The 45.3 ms E180 pulse had MEGA editing effects over a frequency range larger than seen in the singlet-resonance inversion profile. Lactate and threonine in healthy brain were both estimated to be 0.4 ± 0.1 mM, with reference to N-acetylaspartate at 12 mM. CONCLUSION: Narrow-band E180 MEGA editing minimizes threonine contamination of lactate spectra and may improve the ability to detect modest changes in lactate levels.

Antifouling Effects of Superhydrophobic Coating on Sessile Marine Invertebrates.

Biofouling is a significant problem in the aquaculture and marine shipping industries; thus, various antifouling methods have been developed to prevent the resultant economic losses. In the present study, the superhydrophobic surface of a lotus leaf was bio-mimicked to achieve antifouling. Specifically, fabric substrates with and without superhydrophobic coatings on the surface were installed on the Tongyeong yacht in December 2020 (group A) and April 2021 (group B), and the coverage of the attached invertebrates was recorded every month until August 2021. The coverage of solitary ascidians (Ascidiella aspersa and Ciona robusta) and branching bryozoans (Bugula neritina) was lower on the coated substrates than on the non-coated ones, and coating or non-coating was significantly correlated with the extent of coverage. Superhydrophobic substrates with a low surface energy and micro-nano dual structure may be unsuitable for the attachment of larvae. Therefore, superhydrophobic coating is a more effective and simpler method of antifouling for certain taxa than other antifouling strategies. However, the antifouling effect of the superhydrophobic substrate in group A reduced after 5 months from the first installation; thus, the durability of the antifouling coating should be further improved, and solving this problem remains a major task, necessitating further research.

An Efficient Compression Method of Underwater Acoustic Sensor Signals for Underwater Surveillance.

In this paper, we propose a new compression method using underwater acoustic sensor signals for underwater surveillance. Generally, sonar applications that are used for surveillance or ocean monitoring are composed of many underwater acoustic sensors to detect significant sources of sound. It is necessary to apply compression methods to the acquired sensor signals due to data processing and storage resource limitations. In addition, depending on the purposes of the operation and the characteristics of the operating environment, it may also be necessary to apply compression methods of low complexity. Accordingly, in this research, a low-complexity and nearly lossless compression method for underwater acoustic sensor signals is proposed. In the design of the proposed method, we adopt the concepts of quadrature mirror filter (QMF)-based sub-band splitting and linear predictive coding, and we attempt to analyze an entropy coding technique suitable for underwater sensor signals. The experiments show that the proposed method achieves better performance in terms of compression ratio and processing time than popular or standardized lossless compression techniques. It is also shown that the compression ratio of the proposed method is almost the same as that of SHORTEN with a 10-bit maximum mode, and both methods achieve a similar peak signal-to-noise ratio (PSNR) and structural similarity (SSIM) index on average.

Systematic Review: The Impact and Importance of Body Composition in Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Alterations in body composition are common in inflammatory bowel disease [IBD] and have been associated with differences in patient outcomes. We sought to consolidate knowledge on the impact and importance of body composition in IBD. METHODS: We performed a systematic search of MEDLINE, EMBASE and conference proceedings by combining two key research themes: inflammatory bowel disease and body composition. RESULTS: Fifty-five studies were included in this review. Thirty-one focused on the impact of IBD on body composition with a total of 2279 patients with a mean age 38.4 years. Of these, 1071 [47%] were male. In total, 1470 [64.5%] patients had Crohn's disease and 809 [35.5%] had ulcerative colitis. Notably, fat mass and fat-free mass were reduced, and higher rates of sarcopaenia were observed in those with active IBD compared with those in clinical remission and healthy controls. Twenty-four additional studies focused on the impact of derangements in body composition on IBD outcomes. Alterations in body composition in IBD are associated with poorer prognoses including higher rates of surgical intervention, post-operative complications and reduced muscle strength. In addition, higher rates of early treatment failure and primary non-response are seen in patients with myopaenia. CONCLUSIONS: Patients with IBD have alterations in body composition parameters in active disease and clinical remission. The impacts of body composition on disease outcome and therapy are broad and require further investigation. The augmentation of body composition parameters in the clinical setting has the potential to improve IBD outcomes in the future.

Optimization of spectrally selective 180° radiofrequency pulse timings in J-difference editing (MEGA) of lactate.

PURPOSE: J-Difference editing (MEGA) provides an effective spectroscopic means of selectively measuring low-concentration metabolites having weakly coupled spins. The fractional inphase and antiphase coherences are determined by the radiofrequency (RF) pulses and inter-RF pulse intervals of the sequence. We examined the timings of the spectrally selective editing 180° pulses (E180) in MEGA-PRESS to maximize the edited signal amplitude in lactate at 3T. METHODS: The time evolution of the lactate spin coherences was analytically and numerically calculated for non-volume localized and single-voxel localized MEGA sequences. Single-voxel localized MEGA-PRESS simulations and phantom experiments were conducted for echo time (TE) 60-160 ms and for all possible integer-millisecond timings of the E180 pulses. Optimized E180 timings of 144, 103, and 109 ms TEs, tailored with simulation and phantom data, were tested in brain tumor patients in vivo. Lactate signals, broadened to singlet linewidths (~6 Hz), were compared between simulation, phantom, and in vivo data. RESULTS: Theoretical and experimental data indicated consistently that the MEGA-edited signal amplitude and width are sensitive to the E180 timings. In volume-localized MEGA, the lactate peak amplitudes in E180-on and difference spectra were maximized at specific E180 timings for individual TEs, largely due to the chemical-shift displacement effects. The E180 timings for maximum lactate peak amplitude were different from those of maximum inphase coherence in in vivo linewidth situations. CONCLUSION: In in vivo MEGA editing, the E180 pulse timings can be effectively used for manipulating the inphase and antiphase coherences and increasing the edited signal amplitude, following TE optimization.

Ink Formulation and Printing Parameters for Inkjet Printing of Two Dimensional Materials: A Mini Review.

Inkjet printing of two-dimensional (2D) material has been a center of interest for wearable electronics and has become a promising platform for next-generation technologies. Despite the enormous progress made in printed 2D materials, there are still challenges in finding the optimal printing conditions involving the ink formulation and printing parameters. Adequate ink formulation and printing parameters for target 2D materials rely on empirical studies and repeated trials. Therefore, it is essential to compile promising strategies for ink formulation and printing parameters. In this context, this review discusses the optimal ink formulations to prepare stable ink and steady ink jetting and then explores the critical printing parameters for fabricating printed 2D materials of a high quality. The summary and future prospects for inkjet-printed 2D materials are also addressed.

Preoperative imaging of glioblastoma patients using hyperpolarized 13C pyruvate: Potential role in clinical decision making.

BACKGROUND: Glioblastoma remains incurable despite treatment with surgery, radiation therapy, and cytotoxic chemotherapy, prompting the search for a metabolic pathway unique to glioblastoma cells.13C MR spectroscopic imaging with hyperpolarized pyruvate can demonstrate alterations in pyruvate metabolism in these tumors. METHODS: Three patients with diagnostic MRI suggestive of a glioblastoma were scanned at 3 T 1-2 days prior to tumor resection using a 13C/1H dual-frequency RF coil and a 13C/1H-integrated MR protocol, which consists of a series of 1H MR sequences (T2 FLAIR, arterial spin labeling and contrast-enhanced [CE] T1) and 13C spectroscopic imaging with hyperpolarized [1-13C]pyruvate. Dynamic spiral chemical shift imaging was used for 13C data acquisition. Surgical navigation was used to correlate the locations of tissue samples submitted for histology with the changes seen on the diagnostic MR scans and the 13C spectroscopic images. RESULTS: Each tumor was histologically confirmed to be a WHO grade IV glioblastoma with isocitrate dehydrogenase wild type. Total hyperpolarized 13C signals detected near the tumor mass reflected altered tissue perfusion near the tumor. For each tumor, a hyperintense [1-13C]lactate signal was detected both within CE and T2-FLAIR regions on the 1H diagnostic images (P = .008). [13C]bicarbonate signal was maintained or decreased in the lesion but the observation was not significant (P = .3). CONCLUSIONS: Prior to surgical resection, 13C MR spectroscopic imaging with hyperpolarized pyruvate reveals increased lactate production in regions of histologically confirmed glioblastoma.

Spectral fitting strategy to overcome the overlap between 2-hydroxyglutarate and lipid resonances at 2.25 ppm.

PURPOSE: 1 H MRS provides a noninvasive tool for identifying mutations in isocitrate dehydrogenase (IDH). Quantification of the prominent 2-hydroxyglutarate (2HG) resonance at 2.25 ppm is often confounded by the lipid resonance at the same frequency in tumors with elevated lipids. We propose a new spectral fitting approach to separate these overlapped signals, therefore, improving 2HG evaluation. METHODS: TE 97 ms PRESS was acquired at 3T from 42 glioma patients. New lipid basis sets were created, in which the small lipid 2.25-ppm signal strength was preset with reference to the lipid signal at 0.9 ppm, incorporating published fat relaxation data. LCModel fitting using the new lipid bases (Fitting method 2) was conducted along with fitting using the LCModel built-in lipid basis set (Fitting method 1), in which the lipid 2.25-ppm signal is assessed with reference to the lipid 1.3-ppm signal. In-house basis spectra of low-molecular-weight metabolites were used in both fitting methods. RESULTS: Fitting method 2 showed marked improvement in identifying IDH mutational status compared with Fitting method 1. 2HG estimates from Fitting method 2 were overall smaller than those from Fitting method 1, which was because of differential assignment of the signal at 2.25 ppm to lipids. In receiver operating characteristic analysis, Fitting method 2 provided a complete distinction between IDH mutation and wild-type whereas Fitting method 1 did not. CONCLUSION: The data suggest that 1 H MR spectral fitting using the new lipid basis set provides a robust fitting strategy that improves 2HG evaluation in brain tumors with elevated lipids.

Realizing High-Performance Li/Na-Ion Half/Full Batteries via the Synergistic Coupling of Nano-Iron Sulfide and S-doped Graphene.

Iron sulfide (FeS) anodes are plagued by severe irreversibility and volume changes that limit cycle performances. Here, a synergistically coupled hybrid composite, nanoengineered iron sulfide/S-doped graphene aerogel, was developed as high-capacity anode material for Li/Na-ion half/full batteries. The rational coupling of in situ generated FeS nanocrystals and the S-doped rGO aerogel matrix boosted the electronic conductivity, Li+ /Na+ diffusion kinetics, and accommodated the volume changes in FeS. This anode system exhibited excellent long-term cyclability retaining high reversible capacities of 422 (1100 cycles) and 382 mAh g-1 (1600 cycles), respectively, for Li+ and Na+ storage at 5 A g-1 . Full batteries designed with this anode system exhibited 435 (FeS/srGOA||LiCoO2 ) and 455 mAh g-1 (FeS/srGOA||Na0.64 Co0.1 Mn0.9 O2 ). The proposed low-cost anode system is competent with the current Li-ion battery technology and extends its utility for Na+ storage.

Brief mindfulness training increased glutamate metabolism in the anterior cingulate cortex.

Mindfulness meditation has become a promising intervention for promoting health and well-being. Neuroimaging studies have shown its beneficial effects on brain functional activity, connectivity, and structures following months to years of practice. A series of randomized controlled trials indicated that one form of mindfulness meditation, the integrative body-mind training (IBMT) induces brain functional and structural changes in brain regions related to self-control networks such as the anterior cingulate cortex (ACC) after 2-10 h of practice. However, whether IBMT could change brain metabolism in the ACC remains unexplored. Utilizing a noninvasive 3T proton magnetic resonance spectroscopy, our results showed a significant increase in glutamate metabolism in the rostral ACC following 10 h of IBMT, suggesting that brief training not only increases ACC activity and structure, but also induces neurochemical changes in regions of the self-control networks. To our knowledge, this is the first study demonstrating the positive effects on brain metabolism in the ACC following brief intervention, suggesting a potential mechanism and implications of mindfulness meditation in ameliorating disorders such as addiction, depression and schizophrenia, which often involve the dysfunction of self-control networks and glutamatergic system (i.e. lower glutamate metabolism).

Glycine by MR spectroscopy is an imaging biomarker of glioma aggressiveness.

BACKGROUND: High-grade gliomas likely remodel the metabolic machinery to meet the increased demands for amino acids and nucleotides during rapid cell proliferation. Glycine, a non-essential amino acid and intermediate of nucleotide biosynthesis, may increase with proliferation. Non-invasive measurement of glycine by magnetic resonance spectroscopy (MRS) was evaluated as an imaging biomarker for assessment of tumor aggressiveness. METHODS: We measured glycine, 2-hydroxyglutarate (2HG), and other tumor-related metabolites in 35 glioma patients using an MRS sequence tailored for co-detection of glycine and 2HG in gadolinium-enhancing and non-enhancing tumor regions on 3T MRI. Glycine and 2HG concentrations as measured by MRS were correlated with tumor cell proliferation (MIB-1 labeling index), expression of mitochondrial serine hydroxymethyltransferase (SHMT2), and glycine decarboxylase (GLDC) enzymes, and patient overall survival. RESULTS: Elevated glycine was strongly associated with presence of gadolinium enhancement, indicating more rapidly proliferative disease. Glycine concentration was positively correlated with MIB-1, and levels higher than 2.5 mM showed significant association with shorter patient survival, irrespective of isocitrate dehydrogenase status. Concentration of 2HG did not correlate with MIB-1 index. A high glycine/2HG concentration ratio, >2.5, was strongly associated with shorter survival (P < 0.0001). GLDC and SHMT2 expression were detectable in all tumors with glycine concentration, demonstrating an inverse correlation with GLDC. CONCLUSIONS: The data suggest that aggressive gliomas reprogram glycine-mediated one-carbon metabolism to meet the biosynthetic demands for rapid cell proliferation. MRS evaluation of glycine provides a non-invasive metabolic imaging biomarker that is predictive of tumor progression and clinical outcome. KEY POINTS: 1. Glycine and 2-hydroxyglutarate in glioma patients are precisely co-detected using MRS at 3T.2. Tumors with elevated glycine proliferate and progress rapidly.3. A high glycine/2HG ratio is predictive of shortened patient survival.

Spectroscopic markers of neurodegeneration in the mesial prefrontal cortex predict survival in ALS.

Background and objective: N-acetylaspartate (NAA) and myo-inositol (mIns) are spectroscopic markers of neuronal integrity and astrogliosis, respectively. We performed a survival analysis to determine the prognostic value of the NAA/mIns metabolite ratio in ALS after a period of two and five years. Methods: Twenty-four patients with ALS (two with ALS-FTD) were recruited to participate in a high-field MR spectroscopy study of the mesial prefrontal cortex. Univariate and multivariate Cox proportional hazards analyses were used to assess NAA/mIns as a predictor of survival alongside other demographic and clinical measures. Census dates were set at two and five years after the time of MR scan for each patient. Survival curves were calculated using the Kaplan-Meier method. Results: After a five-year observation period, 19 patients had died and five were still alive. Median survival time from date of scan was 1.95 years. Univariate and multivariate Cox analysis showed NAA/mIns to be a significant independent predictor of survival at two years after scanning, but not at five years. Conclusion: Cerebral degeneration in the mesial prefrontal cortex as detected by the NAA/mIns metabolite ratio is predictive of survival in ALS in a time-dependent manner.

In vivo MRS measurement of 2-hydroxyglutarate in patient-derived IDH-mutant xenograft mouse models versus glioma patients.

PURPOSE: To generate a preclinical model of isocitrate dehydrogenase (IDH) mutant gliomas from glioma patients and design a MRS method to test the compatibility of 2-hydroxyglutarate (2HG) production between the preclinical model and patients. METHODS: Five patient-derived xenograft (PDX) mice were generated from two glioma patients with IDH1 R132H mutation. A PRESS sequence was tailored at 9.4 T, with computer simulation and phantom analyses, for improving 2HG detection in mice. 2HG and other metabolites in the PDX mice were measured using the optimized MRS at 9.4 T and compared with 3 T MRS measurements of the metabolites in the parental-tumor patients. Spectral fitting was performed with LCModel using in-house basis spectra. Metabolite levels were quantified with reference to water. RESULTS: The PRESS TE was optimized to be 96 ms, at which the 2HG 2.25 ppm signal was narrow and inverted, thereby leading to unequivocal separation of the 2HG resonance from adjacent signals from other metabolites. The optimized MRS provided precise detection of 2HG in mice compared to short-TE MRS at 9.4 T. The 2HG estimates in PDX mice were in excellent agreement with the 2HG measurements in the patients. CONCLUSION: The similarity of 2HG production between PDX models and parental-tumor patients indicates that PDX tumors retain the parental IDH metabolic fingerprint and can serve as a preclinical model for improving our understanding of the IDH-mutation associated metabolic reprogramming.

Magnetic Resonance Spectroscopic Assessment of Isocitrate Dehydrogenase Status in Gliomas: The New Frontiers of Spectrobiopsy in Neurodiagnostics.

BACKGROUND: In the era of integrated genomic-histologic analysis of brain tumors, new biomarkers have been introduced as diagnostic, prognostic, and therapeutic indicators. The analysis of the mutation in the isocitrate dehydrogenase (IDH) genes IDH1 and IDH2 has provided important diagnostic and prognostic information for patients affected by diffuse glioma (i.e., the presence of the mutation has been related to an increased survival rate). The reference standard of IDH mutation detection has been its assessment in surgical specimens, immunohistochemistry, and/or genetic sequencing. Knowing the IDH status information preoperatively would be of great importance, because it has been related to tumor progression and the response to treatment. The oncometabolite 2-hydroxyglutarate (2HG), accumulated in gliomas with IDH mutation status, can be detected in vivo using magnetic resonance spectroscopy (MRS). METHODS: The 2HG-MRS technique remains technically challenging. We have summarized the results of the first pilot study in Australia, which included 10 patients affected by glioma. The data recorded from May 2017 to November 2018 were analyzed. RESULTS: In our exploratory study, we reached a sensitivity and specificity of 100%, confirming the strong predictive role of 2HG, as detected using MRS, in the diagnosis of glioma. CONCLUSION: In the present study, we have focused on methodological tips and future perspectives of the technique in the neuroimaging and neuro-oncological scenario. We would advocate the integration of 2HG-MRS into standard clinical practice.

High-Definition Chromoendoscopy Versus High-Definition White Light Colonoscopy for Neoplasia Surveillance in Ulcerative Colitis: A Randomized Controlled Trial.

OBJECTIVES: Although chromoendoscopy is currently the recommended mode of surveillance in patients with long-standing ulcerative colitis, it is technically challenging and requires a long procedure time. The aim of this study was to compare the dysplasia detection rate of high-definition white light endoscopy with random biopsy (HDWL-R) vs high-definition chromoendoscopy with targeted biopsy (HDCE-T). METHODS: This was a multicenter, prospective randomized controlled trial involving 9 tertiary teaching hospitals in South Korea. A total of 210 patients with long-standing ulcerative colitis were randomized to undergo either the HDWL-R group (n = 102) or HDCE-T group (n = 108). The detection rates of colitis-associated dysplasia (CAD) or all colorectal neoplasia from each trial arm were compared. RESULTS: There was no significant difference in the CAD detection rate between HDCE-T and HDWL-R groups (4/102, 3.9% vs 6/108, 5.6%, P = 0.749). However, HDCE-T showed a trend toward improved colorectal neoplasia detection compared with HDWL-R (21/102, 20.6% vs 13/108, 12.0%, P = 0.093). The median (range) time for colonoscopy withdrawal between the 2 groups was similar (17.6 [7.0-43.3] minutes vs 16.5 [6.3-38.1] minutes; P=0.212; for HDWL-R and HDCE-T, respectively). The total number of biopsies was significantly larger in the HDWL-R group (34 [12-72]) compared with the HDCE-T group (9 [1-20]; P < 0.001). DISCUSSION: On the basis of our prospective randomized controlled trial, HDCE-T was not superior to HDWL-R for detecting CADs.

A randomized trial of an NMDA receptor antagonist for reversing corticosteroid effects on the human hippocampus.

Preclinical and clinical research indicates that excess corticosteroid is associated with adverse effects on the hippocampus. Animal model data suggest that N-methyl-D-aspartate (NMDA) receptor antagonists may block corticosteroid effect on the hippocampus. This translational clinical trial investigated the effect of memantine vs. placebo on hippocampal subfield volume in humans receiving chronic corticosteroid therapy. Men and women (N = 46) receiving chronic prescription corticosteroid therapy were randomized to memantine or placebo in a double-blind, crossover design (two 24-week treatment periods, separated by a 4-week washout) for 52 weeks. Structural magnetic resonance imaging was obtained at baseline and after each treatment. Data were analyzed using repeated measures analysis of variance. Mean corticosteroid dose was 7.69 ± 6.41 mg/day and mean duration 4.90 ± 5.61 years. Controlling for baseline volumes, the left DG/CA3 region was significantly larger following memantine than placebo (p = .011). The findings suggest that an NMDA receptor antagonist attenuates corticosteroid effect in the same hippocampal subfields in humans as in animal models. This finding has both mechanistic and clinical implications. Attenuation of the effect of corticosteroids on the human DG/CA3 region implicates the NMDA receptor in human hippocampal volume losses with corticosteroids. In addition, by suggesting a drug class that may, at least in part, block the effects of corticosteroids on the human DG/CA3 subfield, these results may have clinical relevance for people receiving prescription corticosteroids, as well as to those with cortisol elevations due to medical or psychiatric conditions.

False-Positive Measurement at 2-Hydroxyglutarate MR Spectroscopy in Isocitrate Dehydrogenase Wild-Type Glioblastoma: A Multifactorial Analysis.

Background Isocitrate dehydrogenase (IDH) mutation has become one of the most important prognostic biomarkers in glioma management. Measurement of 2-hydroxyglutarate (2HG) with MR spectroscopy has shown high pooled sensitivity, although false-positive results with MR spectroscopy have been reported. Purpose To investigate factors associated with false-positive 2HG measurements at MR spectroscopy in patients with IDH wild-type glioblastoma. Materials and Methods This retrospective study was approved by the institutional review board, and informed consent was waived. Consecutive patients with histopathologically confirmed pre- and posttreatment glioblastoma were evaluated between December 2017 and August 2018. Spectroscopy parameters, including 2HG measurements, were obtained with single-voxel point-resolved spectroscopy, and apparent diffusion coefficient (ADC) values were calculated. Necrosis was graded according to the proportion of necrosis within a volume of interest. Poisson regression analyses were performed to determine factors related to false-positive 2HG measurements. Results A total of 82 patients were included (mean age, 55 years ± 12 [standard deviation]; 40 men). The 2HG measurement showed a false-positive rate of 21% (17 of 82; 95% CI: 13%, 31%) in patients with IDH wild-type glioblastoma. Multivariable analysis revealed that necrosis (prevalence ratio [PR], 3.9; 95% CI: 1.6, 9.4; P = .01) and ADC value (PR, 0.1 × 10-3 mm2/sec; 95% CI: [0.0, 0.7] × 10-3 mm2/sec; P = .02) were associated with a greater false-positive rate for the 2HG measurement. Necrosis of more than 20% was associated with a higher rate of false-positive 2HG measurements (50%) than was necrosis of 20% or less (15%, P = .01). The 2HG false-positive rate was higher in patients with pretreatment glioblastoma (46%) than in those with posttreatment glioblastoma (14%, P < .01). Among 17 patients with false-positive findings, 15 (88%; 95% CI: 64%, 99%) had a lactate concentration of 2.0 mmol/L or higher, and 14 (82%, 95% CI: 57%, 96%) had a lactate concentration of 3.0 mmol/L or higher. Conclusion Necrosis and apparent diffusion coefficient were associated with false-positive measurements of 2-hydroxyglutarate at MR spectroscopy in patients with isocitrate dehydrogenase wild-type glioblastoma. © RSNA, 2019 Online supplemental material is available for this article.

A randomized, double-blind, placebo-controlled trial of lamotrigine for prescription corticosteroid effects on the human hippocampus.

In animals, stress and corticosteroid excess are associated with decreases in memory performance and hippocampal volume that may be prevented with agents that decrease glutamate release. Humans also demonstrate changes in memory and hippocampus with corticosteroids. In this report the effects of glutamate-release inhibitor lamotrigine on hippocampal structure and memory were examined in people receiving medically needed prescription corticosteroid therapy. A total of 54 outpatient adults (n = 28 women) receiving chronic (≥ 6 months) oral corticosteroid therapy were randomized to lamotrigine or placebo for 48 weeks. Declarative memory was assessed using the Rey Auditory Verbal Learning Test (RAVLT); structural magnetic resonance imaging (MRI) as well as single-voxel proton MR spectroscopy (1HMRS) focused on hippocampus were obtained at baseline and week 48. Utilizing a mixed-model approach, structural and biochemical data were examined by separate ANOVAs, and memory was assessed with a multi-level longitudinal model. RAVLT total scores demonstrated significantly better declarative memory performance with lamotrigine than placebo (p = 0.047). Hippocampal subfield volumes were not significantly different between the treatment groups. In summary, lamotrigine was associated with less decline in declarative memory performance than placebo in corticosteroid-treated patients. Findings suggest that, in humans as well as in animal models, glutamate release inhibitors may attenuate some of the effects on the human memory associated with corticosteroids.