Clinical Proton MR Spectroscopy in Central Nervous System Disorders.

A large body of published work shows that proton (hydrogen 1 [(1)H]) magnetic resonance (MR) spectroscopy has evolved from a research tool into a clinical neuroimaging modality. Herein, the authors present a summary of brain disorders in which MR spectroscopy has an impact on patient management, together with a critical consideration of common data acquisition and processing procedures. The article documents the impact of (1)H MR spectroscopy in the clinical evaluation of disorders of the central nervous system. The clinical usefulness of (1)H MR spectroscopy has been established for brain neoplasms, neonatal and pediatric disorders (hypoxia-ischemia, inherited metabolic diseases, and traumatic brain injury), demyelinating disorders, and infectious brain lesions. The growing list of disorders for which (1)H MR spectroscopy may contribute to patient management extends to neurodegenerative diseases, epilepsy, and stroke. To facilitate expanded clinical acceptance and standardization of MR spectroscopy methodology, guidelines are provided for data acquisition and analysis, quality assessment, and interpretation. Finally, the authors offer recommendations to expedite the use of robust MR spectroscopy methodology in the clinical setting, including incorporation of technical advances on clinical units. © RSNA, 2014 Online supplemental material is available for this article.

Restricted or severely hindered diffusion of intramyocellular lipids in human skeletal muscle shown by in vivo proton MR spectroscopy

Although magnetic resonance spectroscopy can be used as a unique tool to study molecular diffusion, it is rarely used to measure the diffusion properties of intramyocellular and extramyocellular lipids. Lipids have very low apparent diffusion coefficients (ADCs), which make these measurements difficult and necessitate strong diffusion gradients and long diffusion times. Consequence is that these measurements have inherently low signal-to-noise ratio and are prone to artifacts. The addition of physiological triggering and individual storage and processing of the spectra is seen to be a possible approach to maximize signal intensity and achieve high reproducibility of the experiments. Thus, the optimized measurement protocol was used to investigate the diffusion properties of lipids in human skeletal muscle in vivo. At a diffusion time of about 110 ms, intramyocellular lipids show a significantly lower ADC (2.0 × 10(-6) mm(2)/s, 95% confidence interval 1.10 × 10(-6) to 2.94 × 10(-6) mm(2)/s) than extramyocellular lipids (1.58 × 10(-5) mm(2)/s, 95% confidence interval 1.41 × 10(-5) to 1.75 × 10(-5) mm(2)/s). Because the chemical properties of both lipid pools can be assumed to be similar, the difference can only be attributed to restricted or severely hindered diffusion in the intramyocellular droplets.

Non-water-suppressed proton MR spectroscopy improves spectral quality in the human spinal cord

Magnetic resonance spectroscopy enables insight into the chemical composition of spinal cord tissue. However, spinal cord magnetic resonance spectroscopy has rarely been applied in clinical work due to technical challenges, including strong susceptibility changes in the region and the small cord diameter, which distort the lineshape and limit the attainable signal to noise ratio. Hence, extensive signal averaging is required, which increases the likelihood of static magnetic field changes caused by subject motion (respiration, swallowing), cord motion, and scanner-induced frequency drift. To avoid incoherent signal averaging, it would be ideal to perform frequency alignment of individual free induction decays before averaging. Unfortunately, this is not possible due to the low signal to noise ratio of the metabolite peaks. In this article, frequency alignment of individual free induction decays is demonstrated to improve spectral quality by using the high signal to noise ratio water peak from non-water-suppressed proton magnetic resonance spectroscopy via the metabolite cycling technique. Electrocardiography (ECG)-triggered point resolved spectroscopy (PRESS) localization was used for data acquisition with metabolite cycling or water suppression for comparison. A significant improvement in the signal to noise ratio and decrease of the Cramér Rao lower bounds of all metabolites is attained by using metabolite cycling together with frequency alignment, as compared to water-suppressed spectra, in 13 healthy volunteers.

Clinical Proton MR Spectroscopy in Central Nervous System Disorders.

A large body of published work shows that proton (hydrogen 1 [(1)H]) magnetic resonance (MR) spectroscopy has evolved from a research tool into a clinical neuroimaging modality. Herein, the authors present a summary of brain disorders in which MR spectroscopy has an impact on patient management, together with a critical consideration of common data acquisition and processing procedures. The article documents the impact of (1)H MR spectroscopy in the clinical evaluation of disorders of the central nervous system. The clinical usefulness of (1)H MR spectroscopy has been established for brain neoplasms, neonatal and pediatric disorders (hypoxia-ischemia, inherited metabolic diseases, and traumatic brain injury), demyelinating disorders, and infectious brain lesions. The growing list of disorders for which (1)H MR spectroscopy may contribute to patient management extends to neurodegenerative diseases, epilepsy, and stroke. To facilitate expanded clinical acceptance and standardization of MR spectroscopy methodology, guidelines are provided for data acquisition and analysis, quality assessment, and interpretation. Finally, the authors offer recommendations to expedite the use of robust MR spectroscopy methodology in the clinical setting, including incorporation of technical advances on clinical units. © RSNA, 2014 Online supplemental material is available for this article.

MR spectroscopy in human prostate: in vitro and in vivo measurements to optimize new quantification algorithms

Il cancro della prostata (PCa) è il tumore maligno non-cutaneo più diffuso tra gli uomini ed è il secondo tumore che miete più vittime nei paesi occidentali. La necessità di nuove tecniche non invasive per la diagnosi precoce del PCa è aumentata negli anni. 1H-MRS (proton magnetic resonance spectroscopy) e 1H-MRSI (proton magnetic resonance spectroscopy imaging) sono tecniche avanzate di spettroscopia in risonanza magnetica che permettono di individuare presenza di metaboliti come citrato, colina, creatina e in alcuni casi poliammine in uno o più voxel nel tessuto prostatico. L’abbondanza o l’assenza di uno di questi metaboliti rende possibile discriminare un tessuto sano da uno patologico. Le tecniche di spettroscopia RM sono correntemente utilizzate nella pratica clinica per cervello e fegato, con l’utilizzo di software dedicati per l’analisi degli spettri. La quantificazione di metaboliti nella prostata invece può risultare difficile a causa del basso rapporto segnale/rumore (SNR) degli spettri e del forte accoppiamento-j del citrato. Lo scopo principale di questo lavoro è di proporre un software prototipo per la quantificazione automatica di citrato, colina e creatina nella prostata. Lo sviluppo del programma e dei suoi algoritmi è stato portato avanti all’interno dell’IRST (Istituto Romagnolo per lo Studio e la cura dei Tumori) con l’aiuto dell’unità di fisica sanitaria. Il cuore del programma è un algoritmo iterativo per il fit degli spettri che fa uso di simulazioni MRS sviluppate con il pacchetto di librerie GAMMA in C++. L’accuratezza delle quantificazioni è stata testata con dei fantocci realizzati all’interno dei laboratori dell’istituto. Tutte le misure spettroscopiche sono state eseguite con il nuovo scanner Philips Ingenia 3T, una delle machine di risonanza magnetica più avanzate per applicazioni cliniche. Infine, dopo aver eseguito i test in vitro sui fantocci, sono stati acquisiti gli spettri delle prostate di alcuni volontari sani, per testare se il programma fosse in grado di lavorare in condizioni di basso SNR.

Role of proton MR for the study of muscle lipid metabolism

1H-MR spectroscopy (MRS) of intramyocellular lipids (IMCL) became particularly important when it was recognized that IMCL levels are related to insulin sensitivity. While this relation is rather complex and depends on the training status of the subjects, various other influences such as exercise and diet also influence IMCL concentrations. This may open insight into many metabolic interactions; however, it also requires careful planning of studies in order to control all these confounding influences. This review summarizes various historical, methodological, and practical aspects of 1H-MR spectroscopy (MRS) of muscular lipids. That includes a differentiation of bulk magnetic susceptibility effects and residual dipolar coupling that can both be observed in MRS of skeletal muscle, yet affecting different metabolites in a specific way. Fitting of the intra- (IMCL) and extramyocellular (EMCL) signals with complex line shapes and the transformation into absolute concentrations is discussed. Since the determination of IMCL in muscle groups with oblique fiber orientation or in obese subjects is still difficult, potential improvement with high-resolution spectroscopic imaging or at higher field strength is considered. Fat selective imaging is presented as a possible alternative to MRS and the potential of multinuclear MRS is discussed. 1H-MRS of muscle lipids allows non-invasive and repeated studies of muscle metabolism that lead to highly relevant findings in clinics and patho-physiology.

MR Spectroscopy and Spectroscopic Imaging for Evaluation of Skeletal Muscle Metabolism: Basics and Applications in Metabolic Diseases

Magnetic resonance spectroscopy (MRS) and spectroscopic imaging (MRSI) provide metabolic information on the musculoskeletal system, thus helping to understand the biochemical and pathophysiological nature of numerous diseases. In particular, MRS has been used to study the energy metabolism of muscular tissue since the very beginning of magnetic resonance examinations in humans when small-bore magnets for studies of the limbs became available. Even more than in other organs, the observation of non-proton-nuclei was important in muscle tissue. Spatial localization was less demanding in these studies, however, high temporal resolution was necessary to follow metabolism during exercise and recovery. The observation of high-energy phosphates during and after the application of workload gives insight into oxidative phosphorylation, a process that takes place in the mitochondria and characterizes impaired mitochondrial function. New applications in insulin-resistant patients followed the development of volume-selective 1H-MRS in whole-body magnets. Nowadays, multinuclear MRS and MRSI of the musculoskeletal system provide several windows to vital biochemical pathways noninvasively. It is shown how MRS and MRSI have been used in numerous diseases to characterize an involvement of the muscular metabolism.

MR Spectroscopy Detects Lipid Peaks in Cerebrotendinous Xanthomatosis

CTX is a rare lipid-storage disease. Novel MRS findings from 3 patients, using a short TE, were the presence of lipid peaks at 0.9 and 1.3 ppm in the depth of the cerebellar hemisphere; this might represent an additional marker of disease that is CNS-specific and noninvasive. A decrease in NAA concentration was also detected and attributed to neuroaxonal damage. One patient presented an increase in mlns concentration, pointing to gliosis and astrocytic proliferation.

Lower N-Acetyl-Aspartate Levels in Prefrontal Cortices in Pediatric Bipolar Disorder: A (1)H Magnetic Resonance Spectroscopy Study

Objective: The few studies applying single-voxel(1)H spectroscopy in children and adolescents with bipolar disorder (BD) have reported low N-acetyl-aspartate (NAA) levels in the dorsolateral prefrontal cortex (DLPFC), and high myo-inositol / phosphocreatine plus creatine (PCr+Cr) ratios in the anterior cingulate. The aim of this study was to evaluate NAA, glycerophosphocholine plus phosphocholine (GPC+PC) and PCr+Cr in various frontal cortical areas in children and adolescents with BD. We hypothesized that NAA levels within the prefrontal cortex are lower in BD patients than in healthy controls, indicating neurodevelopmental alterations in the former. Method: We studied 43 pediatric patients with DSM-IV BD (19 female, mean age 13.2 +/- 2.9 years) and 38 healthy controls (79 female, mean age 13.9 +/- 2.7 years). We conducted multivoxel in vivo (1)H spectroscopy measurements at 1.5 Tesla using a long echo time of 272 ms to obtain bilateral metabolite levels from the medial prefrontal cortex (MPFC), DLPFC (white and gray matter), cingulate (anterior and posterior), and occipital lobes. We used the nonparametric Mann-Whitney U test to compare neurochemical levels between groups. Results: In pediatric BD patients, NAA and GPC+PC levels in the bilateral MPFC, and PCr+Cr levels in the left MPFC were lower than those seen in the controls. In the left DLPFC white matter, levels of NAA and PCr+Cr were also lower in BD patients than in controls. Conclusions: Lower NAA and PCr+Cr levels in the PFC of children and adolescents with BD may be indicative of abnormal dendritic arborization and neuropil, suggesting neurodevelopmental abnormalities. J. Am. Acad. Child Adolesc. Psychiatry, 2011;50(1):85-94.

Bipolar disorder comorbid with alcoholism: A (1)H magnetic resonance spectroscopy study

Alcoholism is highly prevalent among bipolar disorder (BD) patients, and its presence is associated with a worse outcome and refractoriness to treatment of the mood disorder. The neurobiological underpinnings that characterize this comorbidity are unknown. We sought to investigate the neurochemical profile of the dorsolateral prefrontal cortex (DLPFC) of BD patients with comorbid alcoholism. A short-TE, single-voxel (1)H spectroscopy acquisition at 1.5T from the left DLFPC of 22 alcoholic BD patients, 26 non-alcoholic BD patients and 54 healthy comparison subjects (HC) were obtained. Absolute levels of N-acetyl aspartate, phosphocreatine plus creatine, choline-containing compounds, myo-inositol, glutamate plus glutamine (Glu + Gln) and glutamate were obtained using the water signal as an internal reference. Analysis of co-variance was used to compare metabolite levels among the three groups. In the primary comparison, non-alcoholic BD patients had higher glutamate concentrations compared to alcoholic BD patients. In secondary comparisons integrating interactions between gender and alcoholism, non-alcoholic BD patients presented significantly higher glutamate plus glutamine (Glu + Gln) than alcoholic BD patients and HC. These results appeared to be driven by differences in male subjects. Alcoholic BD patients with additional drug use disorders presented significantly lower myo-inositol than BD patients with alcoholism alone. The co-occurrence of BD and alcoholism may be characterized by neurochemical abnormalities related to the glutamatergic system and to the inositol second messenger system and/or in glial pathology. These abnormalities may be the neurochemical correlate of an increased risk to develop alcoholism in BD, or of a persistently worse clinical and functional status in BD patients in remission from alcoholism, supporting the clinical recommendation that efforts should be made to prevent or early diagnose and treat alcoholism in BD patients. (C) 2009 Elsevier Ltd. All rights reserved.

The investigation of glutamine and glutamate in the human brain using MR spectroscopy at 7 Tesla

Magdeburg, Univ., Fak. für Naturwiss., Diss., 2014

Are glutamate and lactate increases ubiquitous to physiological activation? A (1)H functional MR spectroscopy study during motor activation in human brain at 7Tesla.

Recent studies at high field (7Tesla) have reported small metabolite changes, in particular lactate and glutamate (below 0.3μmol/g) during visual stimulation. These studies have been limited to the visual cortex because of its high energy metabolism and good magnetic resonance spectroscopy (MRS) sensitivity using surface coil. The aim of this study was to extend functional MRS (fMRS) to investigate for the first time the metabolite changes during motor activation at 7T. Small but sustained increases in lactate (0.17μmol/g±0.05μmol/g, p<0.001) and glutamate (0.17μmol/g±0.09μmol/g, p<0.005) were detected during motor activation followed by a return to the baseline after the end of activation. The present study demonstrates that increases in lactate and glutamate during motor stimulation are small, but similar to those observed during visual stimulation. From the observed glutamate and lactate increase, we inferred that these metabolite changes may be a general manifestation of the increased neuronal activity. In addition, we propose that the measured metabolite concentration increases imply an increase in ΔCMRO2 that is transiently below that of ΔCMRGlc during the first 1 to 2min of the stimulation.

MR spectroscopy of the human brain with enhanced signal intensity at ultrashort echo times on a clinical platform at 3T and 7T.

Recently, the spin-echo full-intensity acquired localized (SPECIAL) spectroscopy technique was proposed to unite the advantages of short TEs on the order of milliseconds (ms) with full sensitivity and applied to in vivo rat brain. In the present study, SPECIAL was adapted and optimized for use on a clinical platform at 3T and 7T by combining interleaved water suppression (WS) and outer volume saturation (OVS), optimized sequence timing, and improved shimming using FASTMAP. High-quality single voxel spectra of human brain were acquired at TEs below or equal to 6 ms on a clinical 3T and 7T system for six volunteers. Narrow linewidths (6.6 +/- 0.6 Hz at 3T and 12.1 +/- 1.0 Hz at 7T for water) and the high signal-to-noise ratio (SNR) of the artifact-free spectra enabled the quantification of a neurochemical profile consisting of 18 metabolites with Cramér-Rao lower bounds (CRLBs) below 20% at both field strengths. The enhanced sensitivity and increased spectral resolution at 7T compared to 3T allowed a two-fold reduction in scan time, an increased precision of quantification for 12 metabolites, and the additional quantification of lactate with CRLB below 20%. Improved sensitivity at 7T was also demonstrated by a 1.7-fold increase in average SNR (= peak height/root mean square [RMS]-of-noise) per unit-time.

Widespread pH abnormalities in patients with malformations of cortical development and epilepsy: a phosphorus-31 brain MR spectroscopy study

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Muscle metabolites: functional MR spectroscopy during exercise imposed by tetanic electrical nerve stimulation

Permission from the ethics committee and informed consent were obtained. The purpose of this study was to prospectively evaluate a method developed for the noninvasive assessment of muscle metabolites during exercise. Hydrogen 1 magnetic resonance (MR) spectroscopy peaks were measured during tetanic isometric muscle contraction imposed by supramaximal repetitive nerve stimulation. The kinetics of creatine-phosphocreatine and acetylcarnitine signal changes (P < .001) could be assessed continuously before, during, and after exercise. The control peak (trimethylammonium compounds), which served as an internal reference, did not change. This technique-that is, functional MR spectroscopy-opens the possibility for noninvasive diagnostic muscle metabolite testing in a clinical setting.