To summarize and evaluate proton ((1)H) and phosphorus ((31)P) magnetic resonance spectroscopy (MRS) findings in migraine.A thorough review of (1)H and/or (31)P-MRS studies in any form of migraine published up to September 2011.Some findings were consistent in all studies, such as a lack of ictal/interictal brain pH change and a disturbed energy metabolism, the latter of which is reflected in a drop in phosphocreatine content, both in the resting brain and in muscle following exercise. In a recent interictal study ATP was found to be significantly decreased in the occipital lobe of migraine with aura patients, reinforcing the concept of a mitochondrial component to the migraine threshold, at least in a subgroup of patients. In several studies a correlation between the extent of the energy disturbance and the clinical phenotype severity was apparent. Less consistent but still congruent with a disturbed energy metabolism is an observed lactate increase in the occipital cortex of several migraine subtypes (MwA, migraine with prolonged aura). No increases in brain glutamate levels were found.The combined abnormalities found in MRS studies imply a mitochondrial component in migraine neurobiology. This could be due to a primary mitochondrial dysfunction or be secondary to, for example, alterations in brain excitability. The extent of variation in the data can be attributed to both the variable clinical inclusion criteria used and the variation in applied methodology. Therefore it is necessary to continue to optimize MRS methodology to gain further insights, especially concerning lactate and glutamate.
Background Improved characterization of healthy muscle aging is needed to establish early biomarkers in age‐related diseases. Purpose To quantify age‐related changes on multiple MRI and clinical variables evaluated in the same cohort and identify correlations among them. Study Type Prospective. Population 70 healthy subjects (30 men) from 20 to 81 years old. Field Strength/Sequence 3T/water T 2 (multiecho SE, multi‐TE STEAM), water T 1 (GRE MR Fingerprinting), fat‐fraction (multiecho GRE, multi‐TE STEAM), carnosine (PRESS), multicomponent water T 2 (ISIS‐CPMG SE train), and 31 P pulse‐acquire spectroscopy. Assessment Age‐ and sex‐related changes on: Imaging: fat‐fraction (FF MRI ), water T 1 (T 1‐H2O ), and T 2 (T 2‐H2O‐MRI ) and their heterogeneities ΔT 1‐H2O and ΔT 2‐H2O‐MRI in the posterior compartment (PC) and anterior compartment (AC) of the leg. 1 H spectroscopy: Carnosine concentration, pH, water T 2 components (T 2‐H2O‐CPMG ), fat‐fraction (FF MRS ), and water T 2 (T 2‐H2O‐MRS ) in the gastrocnemius medialis. 31 P spectroscopy: Phosphodiesters (PDE), phosphomonoesters, inorganic phosphates (Pi), and phosphocreatine (PCr) normalized to adenosine triphosphate (ATP) and pH in the calf. Clinical evaluation: Body‐mass index (BMI), gait speed (GS), plantar flexion strength, handgrip strength (HS), HS normalized to wrist circumference (HS norm ), physical activity assessment. Statistical Tests Multilinear regressions with sex and age as fixed factors. Spearman correlations calculated between variables. Benjamini–Hochberg procedure for false positives reduction (5% rate). A P < 0.05 significance level was used. Results Significant age‐related increases were found for BMI ( ρ Age = 0.04), HS norm ( ρ Age = −0.01), PDE/ATP ( ρ Age = 2.8 × 10 −3 ), Pi/ATP ( ρ Age = 2.0 × 10 −3 ), Pi/PCr ( ρ Age = 0.3 × 10 −3 ), T 2‐H2O‐MRS ( ρ Age = 0.051 msec), FF MRS ( ρ Age = 0.036) the intermediate T 2‐H2O‐CPMG component time ( ρ Age = 0.112 msec), and fraction ( ρ Age = −0.3 × 10 −3 ); and in both compartments for FF MRI ( ρ Age = 0.06, PC; ρ Age = 0.06, AC), T 2‐H2O‐MRI ( ρ Age = 0.05, PC; ρ Age = 0.05, AC; msec), ΔT 2‐H2O‐MRI ( ρ Age = 0.02, PC; ρ Age = 0.02, AC; msec), T 1‐H2O ( ρ Age = 1.08, PC; ρ Age = 1.06, AC; msec), and ΔT 1‐H2O ( ρ Age = 0.22, PC; ρ Age = 0.37, AC; msec). The best age predictors, accounting for sex‐related differences, were HS norm ( R 2 = 0.52) and PDE/ATP ( R 2 = 0.44). In both leg compartments, the imaging measures and HS norm were intercorrelated. In PC, T 2‐H2O‐MRS and FF MRS also showed numerous correlations to the imaging measures. PDE/ATP correlated to T 1‐H2O, T 2‐H2O‐MRI , ΔT 2‐H2O‐MRI , FF MRI , FF MRS , the intermediate T 2‐H2O‐CPMG , BMI, Pi/PCr, and HS norm . Data Conclusion Our multiparametric MRI approach provided an integrative view of age‐related changes in the leg and revealed multiple correlations between these parameters and the normalized HS. Level of Evidence 1 Technical Efficacy Stage 3
The reference standard for assessing water T2 (T2,H2O ) at high fat fraction (FF) is 1 H MRS. T2,H2O (T2,H2O,MRS ) dependence on FF (FFMRS ) has recently been demonstrated in muscle at high FF (i.e. ≥60%).To investigate the relationship between T2,H2O,MRS and FFMRS in the thigh/leg muscles of patients with neuromuscular diseases and to compare with quantitative MRI.Retrospective case-control study.A total of 151 patients with neuromuscular disorders (mean age ± standard deviation = 52.5 ± 22.6 years, 54% male), 44 healthy volunteers (26.5 ± 13.0 years, 57% male).A 3-T; single-voxel stimulated echo acquisition mode (STEAM) MRS, multispin echo (MSE) imaging (for T2 mapping, T2,H2O,MRI ), three-point Dixon imaging (for FFMRI and R2* mapping).Mono-exponential and bi-exponential models were fitted to water T2 decay curves to extract T2,H2O,MRS and FFMRS . Water resonance full-width-at-half-maximum (FWHM) and B0 spread (∆B0 ) values were calculated. T2,H2O,MRI (mean), FFMRI (mean, kurtosis, and skewness), and R2* (mean) values were estimated in the MRS voxel.Mann-Whitney U tests, Kruskal-Wallis tests. A P-value <0.05 was considered statistically significant.Normal T2,H2O,MRS threshold was defined as the 90th percentile in healthy controls: 30.3 msec. T2,H2O,MRS was significantly higher in all patients with FFMRS < 60% compared to healthy controls. We discovered two subgroups in patients with FFMRS ≥ 60%: one with T2,H2O,MRS ≥ 30.3 msec and one with T2,H2O,MRS < 30.3 msec including abnormally low T2,H2O,MRS . The latter subgroup had significantly higher water resonance FWHM, ∆B0 , FFMRI kurtosis, and skewness values but nonsignificantly different R2* (P = 1.00) and long T2,H2O,MRS component and its fraction (P > 0.11) based on the bi-exponential analysis.The findings suggest that the cause for (abnormally) T2,H2O,MRS at high FFMRS is biophysical, due to differences in susceptibility between muscle and fat (increased FWHM and ∆B0 ), rather than pathophysiological such as compartmentation changes, which would be reflected by the bi-exponential analysis.3 TECHNICAL EFFICACY: Stage 3.
Proton magnetic resonance spectroscopy (1H-MRS) has been used in a number of studies to assess noninvasively the temporal changes of lactate (Lac) in the activated human brain. Migraine neurobiology involves lack of cortical habituation to repetitive stimuli and a mitochondrial component has been put forward. Our group has recently demonstrated a reduction in the high-energy phosphates adenosine triphosphate (ATP) and phosphocreatine (PCr) in the occipital lobe of migraine without aura (MwoA) patients, at least in a subgroup, in a phosphorus MRS (31P-MRS) study. In previous studies, basal Lac levels or photic stimulation (PS)-induced Lac levels were found to be increased in patients with migraine with aura (MwA) and migraine patients with visual symptoms and paraesthesia, paresia and/or dysphasia, respectively. The aim of this study was to perform functional 1H-MRS at 3 T in 20 MwoA patients and 20 control subjects. Repetitive visual stimulation was applied using MR-compatible goggles with 8 Hz checkerboard stimulation during 12 min. We did not observe any significant differences in signal integrals, ratios and absolute metabolite concentrations, including Lac, between MwoA patients and controls before PS. Lac also did not increase significantly during and following PS, both for MwoA patients and controls. Subtle Lac changes, smaller than the sensitivity threshold (i.e. estimated at 0.1–0.2 μmol/g at 3 T), cannot be detected by MRS. Our study does, however, argue against a significant switch to non-aerobic glucose metabolism during long-lasting PS of the visual cortex in MwoA patients.
Quantitative MRI and MRS have become important tools for the assessment and management of patients with neuromuscular disorders (NMDs). Despite significant progress, there is a need for new objective measures with improved specificity to the underlying pathophysiological alteration. This would enhance our ability to characterize disease evolution and improve therapeutic development. In this study, qMRI methods that are commonly used in clinical studies involving NMDs, like water T2 (T2
Objective: To examine the concentric ankle dorsiflexion exercise effects on the magnetic resonance imaging (MRI) measure of muscle water T 2 in the lower legs of patients with Duchenne muscular dystrophy (DMD). Background: Surrogate outcome measures are needed to measure therapeutic response in clinical trials of DMD. Absence of dystrophin leads to sarcolemmal fragility with consequent more susceptibility to damage following eccentric exercise. Active movement training can lead to functional improvements. However, the effects of submaximal concentric muscle activity on DMD muscle are not yet known. MRI water T 2 is sensitive to changes of muscle injury or edema, but fatty replacement masks increases in water T 2 in human dystrophic muscle. The tri-exponential model measures muscle water T 2 independent of fat values in skeletal muscle. Design/Methods: In 12 ambulatory DMD boys and 19 healthy volunteer boys, muscle water T 2 was measured at baseline and 3h post concentric ankle dorsiflexion exercise in the lower leg muscles by the tri-exponential model. Muscle fat fraction (FF) was measured by Dixon. Results: The muscle FF was higher in nearly all of the lower leg muscles of DMD participants than the healthy volunteers ( p T 2 was higher in the lower leg muscles of DMD participants than the healthy volunteers ( p p T 2 increased from baseline in the lower legs of both groups. Most prominent T 2 increases were in the ankle dorsiflexor muscles of the DMD participants with a larger inter-subject variability than the healthy volunteers. Conclusions: Skeletal muscle water T 2 measured by the tri-exponential model is a sensitive MRI biomarker related to muscle degeneration and concentric muscle exercise in DMD. Study Supported by: NIH Intramural Funds Disclosure: Dr. Mankodi has nothing to disclose. Dr. Azzabou has nothing to disclose. Dr. Bulea has nothing to disclose. Dr. Reyngoudt has nothing to disclose. Dr. Shimellis has nothing to disclose. Dr. Ren has received personal compensation for activities with RehabTek, Inc., as an employee. Dr. Kim has nothing to disclose. Dr. Fischbeck has nothing to disclose. Dr. Carlier has nothing to disclose.
'%3e%3cpath fill='%23012169' d='M0 0v30h60V0z'/%3e%3cpath stroke='%23fff' stroke-width='6' d='m0 0 60 30m0-30L0 30'/%3e%3cpath stroke='%23C8102E' stroke-width='4' d='m0 0 60 30m0-30L0 30' clip-path='url(%23b)'/%3e%3cpath stroke='%23fff' stroke-width='10' d='M30 0v30M0 15h60'/%3e%3cpath stroke='%23C8102E' stroke-width='6' d='M30 0v30M0 15h60'/%3e%3c/g%3e%3c/svg%3e)
