Measurements of in vivo skeletal muscle oxidative capacity are lower following sustained isometric compared with dynamic contractions.

Human skeletal muscle oxidative capacity can be quantified non-invasively using 31-phosphorus magnetic resonance spectroscopy (31P-MRS) to measure the rate constant of phosphocreatine (PCr) recovery (kPCr) following contractions. In the quadricep muscles, several studies have quantified kPCr following 24-30 s of sustained maximal voluntary isometric contraction (MVIC). This approach has the advantage of simplicity but is potentially problematic because sustained MVICs inhibit perfusion, which may limit muscle oxygen availability or increase the intracellular metabolic perturbation, and thus affect kPCr. Alternatively, dynamic contractions allow reperfusion between contractions, which may avoid limitations in oxygen delivery. To determine whether dynamic contraction protocols elicit greater kPCr than sustained MVIC protocols, we used a cross-sectional design to compare quadriceps kPCr in 22 young and 11 older healthy adults following 24 s of maximal voluntary: (1) sustained MVIC and (2) dynamic (MVDC; 120°·s-1, 1 every 2 s) contractions. Muscle kPCr was ∼20% lower following the MVIC protocol compared with the MVDC protocol (p ≤ 0.001), though this was less evident in older adults (p = 0.073). Changes in skeletal muscle pH (p ≤ 0.001) and PME accumulation (p ≤ 0.001) were greater following the sustained MVIC protocol, and pH (p ≤ 0.001) and PME (p ≤ 0.001) recovery were slower. These results demonstrate that (i) a brief, sustained MVIC yields a lower value for skeletal muscle oxidative capacity than an MVDC protocol of similar duration and (ii) this difference may not be consistent across populations (e.g., young vs. old). Thus, the potential effect of contraction protocol on comparisons of kPCr in different study groups requires careful consideration in the future.

Postcontraction [acetylcarnitine] reflects interindividual variation in skeletal muscle ATP production patterns in vivo.

In addition to its role in substrate selection (carbohydrate vs. fat) for oxidative metabolism in muscle, acetylcarnitine production may be an important modulator of the energetic pathway by which ATP is produced. A combination of noninvasive magnetic resonance spectroscopy measures of cytosolic acetylcarnitine and ATP production pathways was used to investigate the link between [acetylcarnitine] and energy production in vivo. Intracellular metabolites were measured in the vastus lateralis muscle of eight males (mean: 28.4 yr, range: 25-35) during 8 min of incremental, dynamic contractions (0.5 Hz, 2-min stages at 6%, 9%, 12%, and 15% maximal torque) that increased [acetylcarnitine] approximately fivefold from resting levels. ATP production via oxidative phosphorylation, glycolysis, and the creatine kinase reaction was calculated based on phosphorus metabolites and pH. Spearman rank correlations indicated that postcontraction [acetylcarnitine] was positively associated with both absolute (mM) and relative (% total ATP) glycolytic ATP production (rs = 0.95, P = 0.001; rs = 0.93, P = 0.002), and negatively associated with relative (rs = -0.81, P = 0.02) but not absolute (rs = -0.14, P = 0.75) oxidative ATP production. Thus, acetylcarnitine accumulated more when there was a greater reliance on "nonoxidative" glycolysis and a relatively lower contribution from oxidative phosphorylation, reflecting the fate of pyruvate in working skeletal muscle. Furthermore, these data indicate striking interindividual variation in responses to the energy demand of submaximal contractions. Overall, the results of this preliminary study provide novel evidence of the coupling in vivo between ATP production pathways and the carnitine system.NEW & NOTEWORTHY Production of acetylcarnitine from acetyl-CoA and free carnitine may be important for energy pathway regulation in contracting skeletal muscle. Noninvasive magnetic resonance spectroscopy was used to investigate the link between acetylcarnitine and energy production in the vastus lateralis muscle during dynamic contractions (n = 8 individuals). A positive correlation between acetylcarnitine accumulation and "nonoxidative" glycolysis and an inverse relationship with oxidative phosphorylation, provides novel evidence of the coupling between ATP production and the carnitine system in vivo.

Assessing the Dose-Dependent Effects of tDCS on Neurometabolites using Magnetic Resonance Spectroscopy.

Concurrent transcranial direct current stimulation (tDCS) and proton Magnetic Resonance Spectroscopy ( 1 H MRS) experiments have shown up- or downregulation of neurotransmitter concentration. However, effects have been modest applying mostly lower current doses and not all studies found significant effects. Dose of stimulation might be an important variable in eliciting a consistent response. To investigate dose effects of tDCS on neurometabolites, we placed an electrode over the left supraorbital region (with a return electrode over the right mastoid bone) and utilized an MRS voxel (3x3x3cm) that was centered over the anterior cingulate/inferior mesial prefrontal region which is in the path of the current distribution. We conducted 5 epochs of acquisition, each one with a 9:18min acquisition time, and applied tDCS in the third epoch. We observed significant dose and polarity dependent modulation of GABA and to a lesser degree of Glutamine/Glutamate (GLX) with the highest and reliable changes seen with the highest current dose, 5mA (current density 0.39 mA/cm 2 ), during and after the stimulation epoch compared with pre-stimulation baselines. The strong effect on GABA concentration (achieving a mean change of 63% from baseline, more than twice as much as reported with lower doses of stimulation) establishes tDCS-dose as an important parameter in eliciting a regional brain engagement and response. Furthermore, our experimental design in examining tDCS parameters and effects using shorter epochs of acquisitions might constitute a framework to explore the tDCS parameter space further and establish measures of regional engagement by non-invasive brain-stimulation.

Alterations of gray and white matter volumes and cortical thickness in treated HIV-positive patients.

Brain structural changes in HIV identified by voxel-based morphometry (VBM) alone could arise from a variety of causes that are difficult to distinguish without further information, such as cortical thickness (CT), gyrification index (GI) or sulcal depth (SD). Hence, our goal was to assess these additional metrics in HIV using high-resolution 3D T1-weighted images and investigate if surface-based morphometric (SBM) analysis would reveal significant changes in the gray matter (GM) and white matter (WM) volumes combined with alterations in cortical thickness (CT), gyrification index (GI), sulcal depth (SD). T1-w magnetization-prepared-rapid-acquisition gradient-echo (MP-RAGE) scans were acquired in 27 HIV-infected individuals on antiretroviral therapy (ART) and 15 HIV-uninfected healthy controls using a 3T MRI scanner equipped with a 16-channel head "receive" and a quadrature body "transmit" coil. Voxel-based and surface-based morphometric analyses were performed using the MATLAB based SPM Computational Anatomy Toolbox (CAT12.7(1700)). HIV-infected patients showed significantly altered GM and WM volumes, CT, GI, and SD, in multiple brain regions. This study showed the association of altered GM and WM volumes in local brain regions with the changes in region-wise CT, GI and SD measures of HIV-infected patients, especially in the parahippocampal and middle frontal regions as compared to uninfected healthy controls. The outcome of this study suggests that the findings of VBM may not necessarily indicate the volumetric shrinkage or increase alone, but might also be due to altered CT, GI, or SD. Correlation analysis showed a significantly accelerated gray matter loss with age in HIV-infected individuals compared to uninfected healthy controls.

Dictionary learning compressed sensing reconstruction: pilot validation of accelerated echo planar J-resolved spectroscopic imaging in prostate cancer.

OBJECTIVES: This study aimed at developing dictionary learning (DL) based compressed sensing (CS) reconstruction for randomly undersampled five-dimensional (5D) MR Spectroscopic Imaging (3D spatial + 2D spectral) data acquired in prostate cancer patients and healthy controls, and test its feasibility at 8x and 12x undersampling factors. MATERIALS AND METHODS: Prospectively undersampled 5D echo-planar J-resolved spectroscopic imaging (EP-JRESI) data were acquired in nine prostate cancer (PCa) patients and three healthy males. The 5D EP-JRESI data were reconstructed using DL and compared with gradient sparsity-based Total Variation (TV) and Perona-Malik (PM) methods. A hybrid reconstruction technique, Dictionary Learning-Total Variation (DLTV), was also designed to further improve the quality of reconstructed spectra. RESULTS: The CS reconstruction of prospectively undersampled (8x and 12x) 5D EP-JRESI data acquired in prostate cancer and healthy subjects were performed using DL, DLTV, TV and PM. It is evident that the hybrid DLTV method can unambiguously resolve 2D J-resolved peaks including myo-inositol, citrate, creatine, spermine and choline. CONCLUSION: Improved reconstruction of the accelerated 5D EP-JRESI data was observed using the hybrid DLTV. Accelerated acquisition of in vivo 5D data with as low as 8.33% samples (12x) corresponds to a total scan time of 14 min as opposed to a fully sampled scan that needs a total duration of 2.4 h (TR = 1.2 s, 32 [Formula: see text]×16 [Formula: see text]×8 [Formula: see text], 512 [Formula: see text] and 64 [Formula: see text]).

Effects of old age and contraction mode on knee extensor muscle ATP flux and metabolic economy in vivo.

KEY POINTS: We used 31-phosphorus magnetic resonance spectroscopy to quantify in vivo skeletal muscle metabolic economy (ME; mass-normalized torque or power produced per ATP consumed) during three 24 s maximal-effort contraction protocols: (1) sustained isometric (MVIC), (2) intermittent isokinetic (MVDCIsoK ), and (3) intermittent isotonic (MVDCIsoT ) in the knee extensor muscles of young and older adults. ME was not different between groups during the MVIC but was lower in older than young adults during both dynamic contraction protocols. These results are consistent with an increased energy cost of locomotion, but not postural support, with age. The effects of old age on ME were not due to age-related changes in muscle oxidative capacity or ATP flux. Specific power was lower in older than young adults, despite similar total ATP synthesis between groups. Together, this suggests a dissociation between cross-bridge activity and ATP utilization with age. ABSTRACT: Muscle metabolic economy (ME; mass-normalized torque or power produced per ATP consumed) is similar in young and older adults during some isometric contractions, but less is known about potential age-related differences in ME during dynamic contractions. We hypothesized that age-related differences in ME would exist only during dynamic contractions, due to the increased energetic demand of dynamic versus isometric contractions. Ten young (Y; 27.5 ± 3.9 years, 6 men) and 10 older (O; 71 ± 5 years, 5 men) healthy adults performed three 24 s bouts of maximal contractions: (1) sustained isometric (MVIC), (2) isokinetic (120°·s-1 , MVDCIsoK ; 0.5 Hz), and (3) isotonic (load = 20% MVIC, MVDCIsoT ; 0.5 Hz). Phosphorus magnetic resonance spectroscopy of the vastus lateralis muscle was used to calculate ATP flux (mM ATP·s-1 ) through the creatine kinase reaction, glycolysis and oxidative phosphorylation. Quadriceps contractile volume (cm3 ) was measured by MRI. ME was calculated using the torque-time integral (MVIC) or power-time integral (MVDCIsoK and MVDCIsoT ), total ATP synthesis and contractile volume. As hypothesized, ME was not different between Y and O during the MVIC (0.12 ± 0.03 vs. 0.12 ± 0.02 Nm. s. cm-3. mM ATP-1 , mean ± SD, respectively; P = 0.847). However, during both MVDCIsoK and MVDCIsoT , ME was lower in O than Y adults (MVDCIsoK : 0.011 ± 0.003 vs. 0.007 ± 0.002 J. cm-3. mM ATP-1 ; P < 0.001; MVDCIsoT : 0.011 ± 0.002 vs. 0.008 ± 0.002; P = 0.037, respectively), despite similar muscle oxidative capacity, oxidative and total ATP flux in both groups. The lower specific power in older than young adults, despite similar total ATP synthesis between groups, suggests there is a dissociation between cross-bridge activity and ATP utilization with age.

Validity and accuracy of calculating oxidative ATP synthesis in vivo during high-intensity skeletal muscle contractions.

Several methods have been developed for using 31 P-MRS to calculate rates of oxidative ATP synthesis (ATPOX ) during muscular contractions based on assumptions that (1) the ATP cost of force generation (ATPCOST ) remains constant or (2) Michaelis-Menten coupling between cytosolic ADP and ATPOX does not change. However, growing evidence suggests that one, or both, of these assumptions are invalid during high-intensity fatigue protocols. Consequently, there is a need to examine the validity and accuracy of traditional ATPOX calculation methods under these conditions. To address this gap, we measured phosphate concentrations and pH in the vastus lateralis muscle of nine young adults during four rest-contraction-recovery trials lasting 24, 60, 120, and 240 s. The initial velocity of phosphocreatine resynthesis (ViPCr ) following each trial served as the criterion measure of ATPOX because this method makes no assumptions of constant ATPCOST or Michaelis-Menten coupling between changes in cytosolic ADP and ATPOX . Subsequently, we calculated ATPOX throughout the 240 s trial using several traditional calculation methods and compared estimations of ATPOX from each method with time-matched measurements of ViPCr . Method 1, which assumes that ATPCOST does not change, was able to model changes in ViPCr over time, but showed poor accuracy for predicting ViPCr across a wide range of ATPOX values. In contrast, Michaelis-Menten methods, which assume that the relationship between changes in cytosolic ADP and ATPOX remains constant, were invalid because they could not model the decline in ViPCr . However, adjusting these Michaelis-Menten methods for observed changes in maximal ATPOX capacity (i.e., Vmax ) permitted modeling of the decline in ViPCr and markedly improved accuracy. The results of these comprehensive analyses demonstrate that valid, accurate measurements of ATPOX can be obtained during high-intensity contractions by adjusting Michaelis-Menten ATPOX calculations for changes in Vmax observed from baseline to post-fatigue.

Oxidative ATP synthesis in human quadriceps declines during 4 minutes of maximal contractions.

KEY POINTS: During maximal exercise, skeletal muscle metabolism and oxygen consumption remain elevated despite precipitous declines in power. Presently, it is unclear whether these responses are caused by an increased ATP cost of force generation (ATPCOST ) or mitochondrial uncoupling; a process that reduces the efficiency of oxidative ATP synthesis (ATPOX ). To address this gap, we used 31-phosphorus magnetic resonance spectroscopy to measure changes in ATPCOST and ATPOX in human quadriceps during repeated trials of maximal intensity knee extensions lasting up to 4 min. ATPCOST remained unchanged. In contrast, ATPOX plateaued by ∼2 min and then declined (∼15%) over the final 2 min. The maximal capacity for ATPOX (Vmax ), as well as ADP-specific rates of ATPOX , were also significantly diminished. Collectively, these results suggest that mitochondrial uncoupling, and not increased ATPCOST , is responsible for altering the regulation of skeletal muscle metabolism and oxygen consumption during maximal exercise. ABSTRACT: The relationship between skeletal muscle oxygen consumption and power output is augmented during exercise at workloads above the lactate threshold. Potential mechanisms for this response have been hypothesized, including increased ATP cost of force generation (ATPCOST ) and mitochondrial uncoupling, a process that reduces the efficiency of oxidative ATP synthesis (ATPOX ). To test these hypotheses, we used phosphorus magnetic resonance spectroscopy to non-invasively measure changes in phosphate concentrations and pH in the vastus lateralis muscle of nine young adults during repeated trials of maximal, all-out dynamic knee extensions (120°s-1 , 1 every 2 s) lasting 24, 60, 120, and 240 s. ATPOX was measured at each time point from the initial velocity of PCr resynthesis, and ATPCOST was calculated as the sum of ATP synthesized by the creatine and adenylate kinase reactions, non-oxidative glycolysis, ATPOX and net changes in [ATP]. Power output declined in a reproducible manner for all four trials. ATPCOST did not change over time (main effect P = 0.45). ATPOX plateaued from 60 to 120 s and then decreased over the final 120 s (main effect P = 0.001). The maximal capacity for oxidative ATP synthesis (Vmax ), as well as ADP-specific rates of ATPOX , also decreased over time (main effect P = 0.001, both). Collectively, these results demonstrate that prolonged maximal contraction protocols impair oxidative energetics and implicate mitochondrial uncoupling as the mechanism for this response. The causes of mitochondrial uncoupling are presently unknown but may offer a potential explanation for the dissociation between skeletal muscle power output and oxygen consumption during maximal, all-out exercise protocols.

Nuclear magnetic resonance spectroscopy of human body fluids and in vivo magnetic resonance spectroscopy: Potential role in the diagnosis and management of prostate cancer.

Prostate cancer is the most common solid organ cancer in men, and the second most common cause of male cancer-related mortality. It has few effective therapies, and is difficult to diagnose accurately. Prostate-specific antigen (PSA), which is currently the most effective diagnostic tool available, cannot reliably discriminate between different pathologies, and in fact only around 30% of patients found to have elevated levels of PSA are subsequently confirmed to actually have prostate cancer. As such, there is a desperate need for more reliable diagnostic tools that will allow the early detection of prostate cancer so that the appropriate interventions can be applied. Nuclear magnetic resonance (NMR) spectroscopy and magnetic resonance spectroscopy (MRS) are 2 high throughput, noninvasive analytical procedures that have the potential to enable differentiation of prostate cancer from other pathologies using metabolomics, by focusing specifically on certain metabolites which are associated with the development of prostate cancer cells and its progression. The value that this type of approach has for the early detection, diagnosis, prognosis, and personalized treatment of prostate cancer is becoming increasingly apparent. Recent years have seen many promising developments in the fields of NMR spectroscopy and MRS, with improvements having been made to hardware as well as to techniques associated with the acquisition, processing, and analysis of related data. This review focuses firstly on proton NMR spectroscopy of blood serum, urine, and expressed prostatic secretions in vitro, and then on 1- and 2-dimensional proton MRS of the prostate in vivo. Major advances in these fields and methodological principles of data collection, acquisition, processing, and analysis are described along with some discussion of related challenges, before prospects that proton MRS has for future improvements to the clinical management of prostate cancer are considered.

Assessment of Lipid and Metabolite Changes in Obese Calf Muscle Using Multi-Echo Echo-planar Correlated Spectroscopic Imaging.

Obesity-related conditions including heart disease, stroke, and type 2 diabetes are leading causes of preventable death. Recent evidence suggests that altered myocellular lipid metabolism in obesity may lead to increased insulin resistance (IR) that predisposes to these disorders. To test the hypothesis that muscles rich in type I vs. type II muscle fibers would exhibit similar changes in intramyocellular lipid (IMCL) and extramyocellular lipid (EMCL) content in obesity, we utilized a new four-dimensional multi echo echo-planar correlated spectroscopic imaging technique that allows separate determination of IMCL and EMCL content in individual calf muscles in obese vs. normal healthy human subjects. Calf muscles were scanned in 32 obese and 11 healthy subjects using a 3T MRI/MRS scanner, and IR in the obese subjects was documented by glucose tolerance testing. In obese subjects, elevation of both IMCL and EMCL content was observed in the gastrocnemius and tibialis anterior muscles (with mixed type I and II fiber content), while a significant increase in only IMCL content (+48%, p < 0.001) was observed in the soleus muscle (predominantly type I fibers). These observations indicate unexpected differences in changes in myolipid metabolism in type I vs. type II rich muscle regions in obesity, perhaps related to IR, and warrant further investigation.

Echo-Planar J-resolved Spectroscopic Imaging using Dual Read-outs: Implementation and Quantitation of Human Brain Metabolites.

Attempts have been made to reduce the total scan time in multi-dimensional J-resolved spectroscopic imaging (JRESI) using an echo-planar (EP) readout gradient, but acquisition duration remains a limitation for routine clinical use in the brain. We present here a significant acceleration achieved with a 4D EP-JRESI sequence that collects dual phase encoded lines within a single repetition time (TR) using two bipolar read-out trains. The performance and reliability of this novel 4D sequence, called Multi-Echo based Echo-Planar J-resolved Spectroscopic Imaging (ME-EP-JRESI), was evaluated in 10 healthy controls and a brain phantom using a 3 T MRI/MRS scanner. The prior knowledge fitting (ProFit) algorithm, with a new simulated basis set consisting of macromolecules and lipids apart from metabolites of interest, was used for quantitation. Both phantom and in-vivo data demonstrated that localization and spatial/spectral profiles of metabolites from the ME-EP-JRESI sequence were in good agreement with that of the EP-JRESI sequence. Both in the occipital and temporal lobe, metabolites with higher physiological concentrations including Glx (Glu+Gln), tNAA (NAA+NAAG), mI all had coefficient of variations between 9-25%. In summary, we have implemented, validated and tested the ME-EP-JRESI sequence, demonstrating that multi-echo acquisition can successfully reduce the total scan duration for EP-JRESI sequences.

Non-uniformly weighted sampling for faster localized two-dimensional correlated spectroscopy of the brain in vivo.

Two-dimensional localized correlated spectroscopy (2D L-COSY) offers greater spectral dispersion than conventional one-dimensional (1D) MRS techniques, yet long acquisition times and limited post-processing support have slowed its clinical adoption. Improving acquisition efficiency and developing versatile post-processing techniques can bolster the clinical viability of 2D MRS. The purpose of this study was to implement a non-uniformly weighted sampling (NUWS) scheme for faster acquisition of 2D-MRS. A NUWS 2D L-COSY sequence was developed for 7T whole-body MRI. A phantom containing metabolites commonly observed in the brain at physiological concentrations was scanned ten times with both the NUWS scheme of 12:48 duration and a 17:04 constant eight-average sequence using a 32-channel head coil. 2D L-COSY spectra were also acquired from the occipital lobe of four healthy volunteers using both the proposed NUWS and the conventional uniformly-averaged L-COSY sequence. The NUWS 2D L-COSY sequence facilitated 25% shorter acquisition time while maintaining comparable SNR in humans (+0.3%) and phantom studies (+6.0%) compared to uniform averaging. NUWS schemes successfully demonstrated improved efficiency of L-COSY, by facilitating a reduction in scan time without affecting signal quality.

Accelerated Echo Planer J-resolved Spectroscopic Imaging of Putamen and Thalamus in Obstructive Sleep Apnea.

UNLABELLED: Obstructive sleep apnea syndrome (OSAS) leads to neurocognitive and autonomic deficits that are partially mediated by thalamic and putamen pathology. We examined the underlying neurochemistry of those structures using compressed sensing-based 4D echo-planar J-resolved spectroscopic imaging (JRESI), and quantified values with prior knowledge fitting. Bilaterally increased thalamic mI/Cr, putamen Glx/Cr, and Glu/Cr, and bilaterally decreased thalamic and putamen tCho/Cr and GABA/Cr occurred in OSAS vs healthy subjects (p < 0.05). Increased right thalamic Glx/Cr, Glu/Cr, Gln/Cr, Asc/Cr, and decreased GPC/Cr and decreased left thalamic tNAA/Cr, NAA/Cr were detected. The right putamen showed increased mI/Cr and decreased tCho/Cr, and the left, decreased PE/Cr ratio. ROC curve analyses demonstrated 60-100% sensitivity and specificity for the metabolite ratios in differentiating OSAS vs. CONTROLS: Positive correlations were found between: left thalamus mI/Cr and baseline oxygen saturation (SaO2); right putamen tCho/Cr and apnea hypopnea index; right putamen GABA/Cr and baseline SaO2; left putamen PE/Cr and baseline SaO2; and left putamen NAA/Cr and SaO2 nadir (all p < 0.05). Negative correlations were found between left putamen PE/Cr and SaO2 nadir. These findings suggest underlying inflammation or glial activation, with greater alterations accompanying lower oxygen saturation. These metabolite levels may provide biomarkers for future neurochemical interventions by pharmacologic or other means.

Non-invasive detection of 2-hydroxyglutarate in IDH-mutated gliomas using two-dimensional localized correlation spectroscopy (2D L-COSY) at 7 Tesla.

BACKGROUND: Mutations in the isocitrate dehydrogenase enzyme are present in a majority of lower-grade gliomas and secondary glioblastomas. This mis-sense mutation results in the neomorphic reduction of isocitrate dehydrogenase resulting in an accumulation of the "oncometabolite" 2-hydroxyglutarate (2HG). Detection of 2HG can thus serve as a surrogate biomarker for these mutations, with significant translational implications including improved prognostication. Two dimensional localized correlated spectroscopy (2D L-COSY) at 7T is a highly-sensitive non-invasive technique for assessing brain metabolism. This study aims to assess tumor metabolism using 2D L-COSY at 7T for the detection of 2HG in IDH-mutant gliomas. METHODS: Nine treatment-naïve patients with suspected intracranial neoplasms were scanned at 7T MRI/MRS scanner using the 2D L-COSY technique. 2D-spectral processing and analyses were performed using a MATLAB-based reconstruction algorithm. Cross and diagonal peak volumes were quantified in the 2D L-COSY spectra and normalized with respect to the creatine peak at 3.0 ppm and quantified data were compared with previously-published data from six normal subjects. Detection of 2HG was validated using findings from immunohistochemical (IHC) staining in patients who subsequently underwent surgical resection. RESULTS: 2HG was detected in both of the IDH-mutated gliomas (grade III Anaplastic Astrocytoma and grade II Diffuse Astrocytoma) and was absent in IDH wild-type gliomas and in a patient with breast cancer metastases. 2D L-COSY was also able to resolve complex and overlapping resonances including phosphocholine (PC) from glycerophosphocholine (GPC), lactate (Lac) from lipids and glutamate (Glu) from glutamine (Gln). CONCLUSIONS: This study demonstrates the ability of 2D L-COSY to unambiguously detect 2HG in addition to other neuro metabolites. These findings may aid in establishing 2HG as a biomarker of malignant progression as well as for disease monitoring in IDH-mutated gliomas.

Obstructive sleep apnea is associated with low GABA and high glutamate in the insular cortex.

The insular cortex is injured in obstructive sleep apnea (OSA) and responds inappropriately to autonomic challenges, suggesting neural reorganization. The objective of this study was to assess whether the neural changes might result from γ-aminobutyric acid (GABA) and glutamate alterations. We studied 14 OSA patients [mean age ± standard deviation (SD): 47.5 ± 10.5 years; nine male; apnea-hypopnea index (AHI): 29.5 ± 15.6 events h(-1) ] and 22 healthy participants (47.5 ± 10.1 years; 11 male), using magnetic resonance spectroscopy to detect GABA and glutamate levels in insular cortices. We localized the cortices with anatomical scans, and measured neurochemical levels from anterior to mid-regions. Left and right anterior insular cortices showed lower GABA and higher glutamate in OSA versus healthy subjects [GABA left: OSA n = 6: 0.36 ± 0.10 (mean ± SD), healthy n = 5: 0.62 ± 0.18; P < 0.05), right: OSA n = 11: 0.27 ± 0.09, healthy n = 14: 0.45 ± 0.16; P < 0.05; glutamate left: OSA n = 6: 1.61 ± 0.32, healthy n = 8: 0.94 ± 0.34; P < 0.05, right: OSA n = 14: 1.26 ± 0.28, healthy n = 19: 1.02 ± 0.28; P < 0.05]. GABA and glutamate levels were correlated only within the healthy group in the left insula (r: -0.9, P < 0.05). The altered anterior insular levels of GABA and glutamate may modify integration and projections to autonomic areas, contributing to the impaired cardiovascular regulation in OSA.

Accelerated echo planar J-resolved spectroscopic imaging in prostate cancer: a pilot validation of non-linear reconstruction using total variation and maximum entropy.

The overlap of metabolites is a major limitation in one-dimensional (1D) spectral-based single-voxel MRS and multivoxel-based MRSI. By combining echo planar spectroscopic imaging (EPSI) with a two-dimensional (2D) J-resolved spectroscopic (JPRESS) sequence, 2D spectra can be recorded in multiple locations in a single slice of prostate using four-dimensional (4D) echo planar J-resolved spectroscopic imaging (EP-JRESI). The goal of the present work was to validate two different non-linear reconstruction methods independently using compressed sensing-based 4D EP-JRESI in prostate cancer (PCa): maximum entropy (MaxEnt) and total variation (TV). Twenty-two patients with PCa with a mean age of 63.8 years (range, 46-79 years) were investigated in this study. A 4D non-uniformly undersampled (NUS) EP-JRESI sequence was implemented on a Siemens 3-T MRI scanner. The NUS data were reconstructed using two non-linear reconstruction methods, namely MaxEnt and TV. Using both TV and MaxEnt reconstruction methods, the following observations were made in cancerous compared with non-cancerous locations: (i) higher mean (choline + creatine)/citrate metabolite ratios; (ii) increased levels of (choline + creatine)/spermine and (choline + creatine)/myo-inositol; and (iii) decreased levels of (choline + creatine)/(glutamine + glutamate). We have shown that it is possible to accelerate the 4D EP-JRESI sequence by four times and that the data can be reliably reconstructed using the TV and MaxEnt methods. The total acquisition duration was less than 13 min and we were able to detect and quantify several metabolites.

Neuroimaging abnormalities, neurocognitive function, and fatigue in patients with hepatitis C.

OBJECTIVE: This study examined neurologic abnormalities (as measured by proton magnetic resonance spectroscopy imaging and diffusion tensor imaging), neurocognitive performance, and fatigue among a sample of adults with hepatitis C virus (HCV). We hypothesized that HCV+ individuals would demonstrate structural brain abnormalities and neurocognitive compromise consistent with frontostriatal dysfunction as well as increased fatigue compared to controls. METHOD: Participants were 76 individuals diagnosed with HCV and 20 controls who underwent a comprehensive neurocognitive evaluation and clinical assessments. A subset of the HCV+ participants (n = 29) and all controls underwent MRI. RESULTS: Individuals diagnosed with chronic HCV infection demonstrated greater fractional anisotropy in the striatum as well as greater mean diffusivity in the fronto-occiptal fasciculus and external capsule compared to HCV- controls. HCV+ participants also demonstrated lower levels of N-acetylaspartate in bilateral parietal white matter and elevations in myo-inosital (mI) in bilateral frontal white matter compared to HCV- controls (all p values < 0.05). HCV+ participants also demonstrated significantly poorer neuropsychological performance, particularly in processing speed and verbal fluency. HCV+ patients reported higher levels of fatigue than controls, and fatigue was significantly correlated with diffusivity in the superior fronto-occipital fasciculus, elevations in mI in frontal white matter, and overall cognitive performance. CONCLUSIONS: Our results suggest that HCV-associated neurologic complications disrupt frontostriatal structures, which may result in increased fatigue and poorer cognitive performance, particularly in those cognitive domains regulated by frontostriatal regions.

A pilot validation of multi-echo based echo-planar correlated spectroscopic imaging in human calf muscles.

A current limitation of MR spectroscopic imaging of multiple skeletal muscles is prolonged scan duration. A significant reduction in the total scan duration using the echo-planar correlated spectroscopic imaging (EP-COSI) sequence was accomplished using two bipolar readout trains with different phase-encoded echoes for one of two spatial dimensions within a single repetition time (TR). The second bipolar readout was used for spatially encoding the outer k-space, whereas the first readout was used for the central k-space only. The performance of this novel sequence, called multi-echo based echo-planar correlated spectroscopic imaging (ME-EPCOSI), was demonstrated by localizing specific key features in calf muscles and bone marrow of 11 healthy volunteers and five subjects with type 2 diabetes (T2D). A 3 T MRI-MRS scanner equipped with a transmit-receive extremity coil was used. Localization of the ME-EPCOSI sequence was in good agreement with the earlier single-readout based EP-COSI sequence and the required scan time was reduced by a factor of two. In agreement with an earlier report using single-voxel based 2D MRS, significantly increased unsaturated pools of intramyocellular lipid (IMCL) and extramyocellular lipid (EMCL) and decreased IMCL and EMCL unsaturation indices (UIs) were observed in the soleus and tibialis anterior muscle regions of subjects with T2D compared with healthy controls. In addition, significantly decreased choline content was observed in the soleus of T2D subjects compared with healthy controls. Multi-voxel characterization of IMCL and EMCL ratios and UI in the calf muscle may be useful for the non-invasive assessment of altered lipid metabolism in the pathophysiology of T2D.

Regional brain gray and white matter changes in perinatally HIV-infected adolescents.

Despite the success of antiretroviral therapy (ART), perinatally infected HIV remains a major health problem worldwide. Although advance neuroimaging studies have investigated structural brain changes in HIV-infected adults, regional gray matter (GM) and white matter (WM) volume changes have not been reported in perinatally HIV-infected adolescents and young adults. In this cross-sectional study, we investigated regional GM and WM changes in 16 HIV-infected youths receiving ART (age 17.0 ± 2.9 years) compared with age-matched 14 healthy controls (age 16.3 ± 2.3 years) using magnetic resonance imaging (MRI)-based high-resolution T1-weighted images with voxel based morphometry (VBM) analyses. White matter atrophy appeared in perinatally HIV-infected youths in brain areas including the bilateral posterior corpus callosum (CC), bilateral external capsule, bilateral ventral temporal WM, mid cerebral peduncles, and basal pons over controls. Gray matter volume increase was observed in HIV-infected youths for several regions including the left superior frontal gyrus, inferior occipital gyrus, gyrus rectus, right mid cingulum, parahippocampal gyrus, bilateral inferior temporal gyrus, and middle temporal gyrus compared with controls. Global WM and GM volumes did not differ significantly between groups. These results indicate WM injury in perinatally HIV-infected youths, but the interpretation of the GM results, which appeared as increased regional volumes, is not clear. Further longitudinal studies are needed to clarify if our results represent active ongoing brain infection or toxicity from HIV treatment resulting in neuronal cell swelling and regional increased GM volume. Our findings suggest that assessment of regional GM and WM volume changes, based on VBM procedures, may be an additional measure to assess brain integrity in HIV-infected youths and to evaluate success of current ART therapy for efficacy in the brain.