Proton spectroscopy can noninvasively provide useful information on brain tumor type and grade. Short- (30 ms) and long- (136 ms) echo time (TE) (1)H spectra were acquired from normal white matter (NWM), meningiomas, grade II astrocytomas, anaplastic astrocytomas, glioblastomas, and metastases. Very low myo-Inositol ([mI]) and creatine ([Cr]) were characteristic of meningiomas, and high [mI] characteristic of grade II astrocytomas. Tumor choline ([Cho]) was greater than NWM and increased with grade for grade II and anaplastic astrocytomas, but was highly variable for glioblastomas. Higher [Cho] and [Cr] correlated with low lipid and lactate (P < 0.05), indicating a dilution of metabolite concentrations due to necrosis in high-grade tumors. Metabolite peak area ratios showed no correlation with lipids and mI/Cho (at TE = 30 ms), and Cr/Cho (at TE = 136 ms) best correlated with tumor grade. The quantified lipid, macromolecule, and lactate levels increased with grade of tumor, consistent with progression from hypoxia to necrosis. Quantification of lipids and macromolecules at short TE provided a good marker for tumor grade, and a scatter plot of the sum of alanine, lactate, and delta 1.3 lipid signals vs. mI/Cho provided a simple way to separate most tumors by type and grade.

The on‐ and off‐transient (i.e. phase II) responses of pulmonary oxygen uptake (V̇O2) to moderate‐intensity exercise (i.e. below the lactate threshold, θL) in humans has been shown to conform to both mono‐exponentiality and ‘on‐off’ symmetry, consistent with a system manifesting linear control dynamics. However above θL the V̇O2 kinetics have been shown to be more complex: during high‐intensity exercise neither mono‐exponentiality nor ‘on‐off’ symmetry have been shown to appropriately characterise the V̇O2 response. Muscle [phosphocreatine] ([PCr]) responses to exercise, however, have been proposed to be dynamically linear with respect to work rate, and to demonstrate ‘on‐off’ symmetry at all work intenisties. We were therefore interested in examining the kinetic characteristics of the V̇O2 and [PCr] responses to moderate‐ and high‐intensity knee‐extensor exercise in order to improve our understanding of the factors involved in the putative phosphate‐linked control of muscle oxygen consumption. We estimated the dynamics of intramuscular [PCr] simultaneously with those of V̇O2 in nine healthy males who performed repeated bouts of both moderate‐ and high‐intensity square‐wave, knee‐extension exercise for 6 min, inside a whole‐body magnetic resonance spectroscopy (MRS) system. A transmit‐receive surface coil placed under the right quadriceps muscle allowed estimation of intramuscular [PCr]; V̇O2 was measured breath‐by‐breath using a custom‐designed turbine and a mass spectrometer system. For moderate exercise, the kinetics were well described by a simple mono‐exponential function (following a short cardiodynamic phase for V̇O2,), with time constants (τ) averaging: τV̇O2,on 35 ± 14 s (±s.d.), τ[PCr]on 33 ± 12 s, τV̇O2,off 50 ± 13 s and τ[PCr]off 51 ± 13 s. The kinetics for both V̇O2 and [PCr] were more complex for high‐intensity exercise. The fundamental phase expressing average τ values of τV̇O2,on 39 ± 4 s, τ[PCr]on 38 ± 11 s, τV̇O2,off 51 ± 6 s and τ[PCr]off 47 ± 11 s. An associated slow component was expressed in the on‐transient only for both V̇O2 and [PCr], and averaged 15.3 ± 5.4 and 13.9 ± 9.1 % of the fundamental amplitudes for V̇O2 and [PCr], respectively. In conclusion, the τ values of the fundamental component of [PCr] and V̇O2 dynamics cohere to within 10 %, during both the on‐ and off‐transients to a constant‐load work rate of both moderate‐ and high‐intensity exercise. On average, ≈90 % of the magnitude of the V̇O2 slow component during high‐intensity exercise is reflected within the exercising muscle by its [PCr] response.

Proton MRS (1H MRS) provides noninvasive, quantitative metabolite profiles of tissue and has been shown to aid the clinical management of several brain diseases. Although most modern clinical MR scanners support MRS capabilities, routine use is largely restricted to specialized centers with good access to MR research support. Widespread adoption has been slow for several reasons, and technical challenges toward obtaining reliable good‐quality results have been identified as a contributing factor. Considerable progress has been made by the research community to address many of these challenges, and in this paper a consensus is presented on deficiencies in widely available MRS methodology and validated improvements that are currently in routine use at several clinical research institutions. In particular, the localization error for the PRESS localization sequence was found to be unacceptably high at 3 T, and use of the semi‐adiabatic localization by adiabatic selective refocusing sequence is a recommended solution. Incorporation of simulated metabolite basis sets into analysis routines is recommended for reliably capturing the full spectral detail available from short TE acquisitions. In addition, the importance of achieving a highly homogenous static magnetic field (B0) in the acquisition region is emphasized, and the limitations of current methods and hardware are discussed. Most recommendations require only software improvements, greatly enhancing the capabilities of clinical MRS on existing hardware. Implementation of these recommendations should strengthen current clinical applications and advance progress toward developing and validating new MRS biomarkers for clinical use.

A computer-based decision support system to assist radiologists in diagnosing and grading brain tumours has been developed by the multi-centre INTERPRET project. Spectra from a database of 1 H single-voxel spectra of different types of brain tumours, acquired in vivo from 334 patients at four different centres, are clustered according to their pathology, using automated pattern recognition techniques and the results are presented as a two-dimensional scatterplot using an intuitive graphical user interface (GUI). Formal quality control procedures were performed to standardize the performance of the instruments and check each spectrum, and teams of expert neuroradiologists, neurosurgeons, neurologists and neuropathologists clinically validated each case. The prototype decision support system (DSS) successfully classified 89% of the cases in an independent test set of 91 cases of the most frequent tumour types (meningiomas, low-grade gliomas and high-grade malignant tumours-glioblastomas and metastases). It also helps to resolve diagnostic difficulty in borderline cases. When the prototype was tested by radiologists and other clinicians it was favourably received. Results of the preliminary clinical analysis of the added value of using the DSS for brain tumour diagnosis with MRS showed a small but significant improvement over MRI used alone. In the comparison of individual pathologies, PNETs were significantly better diagnosed with the DSS than with MRI alone.

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.q RSNA, 2014 Online supplemental material is available for this article. G.O. (e-mail: gulin@cmrr.umn.edu). 2 The complete list of authors and affiliations is at the end of this article.q RSNA, 2014 Note: This copy is for your personal non-commercial use only. To order presentation-ready copies for distribution to your colleagues or clients, contact us at www.rsna.org/rsnarights. Radiology H MR Spectrum of the Brain: Metabolites and Their Biomarker PotentialMR spectroscopy provides a very different basic "readout" than MR imaging, namely a spectrum rather than an techniques were developed. These early localization techniques included pointresolved spectroscopy (PRESS) (1,2) and stimulated echo acquisition mode (STEAM) (3), methods that are now widely used in clinical MR spectroscopy applications.Preliminary studies revealed large differences in metabolite levels in acute stroke (4), chronic multiple sclerosis (5), and brain tumors compared with healthy brain (6). Although this work stimulated a surge of interest in 1 H MR spectroscopy for diagnosing and assessing CNS disorders during the early days of the "Decade of the Brain" (1990)(1991)(1992)(1993)(1994)(1995)(1996)(1997)(1998)(1999), many suboptimal patient studies (7) and the lack of consistent guidelines have led to a situation where, 20 years later, MR spectroscopy is still considered an "investigational technique" by some medical professionals and health care organizations. However, the ability to make an early, noninvasive diagnosis or to increase confidence in a suspected diagnosis is highly valued by patients and clinicians alike. As a result, an increasing number of imaging centers are incorporating MR spectroscopy into their clinical protocols for brain...

In the non‐steady state of moderate intensity exercise, pulmonary O2 uptake (V̇p,O2) is temporally dissociated from muscle O2 consumption (V̇m,O2) due to the influence of the intervening venous blood volume and the contribution of body O2 stores to ATP synthesis. A monoexponential model of V̇p,O2 without a delay term, therefore, implies an obligatory slowing of V̇p,O2 kinetics in comparison to V̇m,O2. During moderate exercise, an association of V̇m,O2 and [phosphocreatine] ([PCr]) kinetics is a necessary consequence of the control of muscular oxidative phosphorylation mediated by some function of [PCr]. It has also been suggested that the kinetics of V̇p,O2 will be expressed with a time constant within 10 % of that of V̇m,O2. V̇p,O2 and intramuscular [PCr] kinetics were investigated simultaneously during moderate exercise of a large muscle mass in a whole‐body NMR spectrometer. Six healthy males performed prone constant‐load quadriceps exercise. A transmit‐receive coil under the right quadriceps allowed determination of intramuscular [PCr]; V̇p,O2 was measured breath‐by‐breath, in concert with [PCr], using a turbine and a mass spectrometer system. Intramuscular [PCr] decreased monoexponentially with no delay in response to exercise. The mean of the time constants (τPCr) was 35 s (range, 20–64 s) for the six subjects. Two temporal phases were evident in the V̇p,O2 response. When the entire V̇p,O2 response was modelled to be exponential with no delay, its time constant (τ′V̇p,O2) was longer in all subjects (group mean = 62 s; range, 52–92 s) than that of [PCr], reflecting the energy contribution of the O2 stores. Restricting the V̇p,O2 model fit to phase II resulted in matching kinetics for V̇p,O2 (group mean τV̇p,O2= 36 s; range, 20–68 s) and [PCr], for all subjects. We conclude that during moderate intensity exercise the phase II τV̇p,O2 provides a good estimate of τPCr and by implication that of V̇m,O2 (τV̇m,O2).

The results are consistent with white matter damage due to axonal loss, causing age- related cognitive decline. Working memory may be particularly dependent on complex networks dependent on white matter connections.

The dynamics of the pulmonary oxygen uptake (V O 2 ) response to muscular exercise are a crucial determinant of exercise tolerance. The mean response time (rfi) of the V O 2 increase during the transient and the asymptotic increment (∆V O 2 ss ) are both determinants of the oxygen deficit and, hence, of the potential requirement for anaerobiosis to supplement the ongoing aerobic component of the energy transfer for muscle contraction. During 'moderate-intensity' square-wave cycle ergometer exercise (i.e. for work rates below the lactate threshold,  L ) the V O 2 response approaches the new steady state with an exponential time course, after a short delay-like period (phase I, e.g. Hughson & Morrissey, 1982;Whipp et al. 1982). The subsequent time constant of this fundamental or phase II component (r) has been proposed to reflect that of O 2 consumption in the exercising muscle (« Q O 2 ) (Barstow et al. 1990;Grassi et al. 1996;Rossiter et al. 1999). The phase II V O 2 kinetics in this work rate range are commonly considered to be determined by intramuscular enzyme kinetics (e.g. Chance et al. 1985;Meyer, 1988). However, an alternative proposition argues for the mediation of V O 2 through the rate of oxygen delivery to the exercising muscle (Hughson et al. 1993;MacDonald et al. 1997 1. A prior bout of high-intensity square-wave exercise can increase the temporal adaptation of pulmonary oxygen uptake (V O 2 ) to a subsequent bout of high-intensity exercise. The mechanisms controlling this adaptation, however, are poorly understood. We therefore determined the dynamics of intramuscular [phosphocreatine] ([PCr])simultaneously with those of V O 2 in seven males who performed two consecutive bouts of high-intensity square-wave, knee-extensor exercise in the prone position for 6 min with a 6 min rest interval. A magnetic resonance spectroscopy (MRS) transmit-receive surface coil under the quadriceps muscle allowed estimation of [PCr]; V O 2 was measured breath-by-breath using a custom-designed turbine and a mass spectrometer system.3. The V O 2 kinetics of the second exercise bout were altered compared with the first such that (a) not only was the instantaneous rate of V O 2 change (at a given level of V O 2 ) greater but the phase II r was also reduced -averaging 46.6 ± 6.0 s (bout 1) and 40.7 ± 8.4 s (bout 2) (mean ± S.D.) and (b) the magnitude of the later slow component was reduced. 4. This was associated with a reduction of, on average, 16.1 % in the total exercise-induced [PCr] decrement over the 6 min of the exercise, of which 4.0 % was due to a reduction in the slow component of [PCr]. There was no discernable alteration in the initial rate of [PCr] change. The prior exercise, therefore, changed the multi-compartment behaviour towards that of functionally first-order dynamics.5. These observations demonstrate that the V O 2 responses relative to the work rate input for highintensity exercise are non-linear, as are, it appears, the putative phosphate-linked controllers for which [PCr] serves as a surrogate.