Valeria Clementi

Deficit of in vivo mitochondrial ATP production in OPA1-related dominant optic atrophy.

Dominant optic atrophy has been associated with mutations in the OPA1 gene, which encodes for a dynamin‐related GTPase, a mitochondrial protein implicated in the formation and maintenance of mitochondrial network and morphology. We used phosphorus magnetic resonance spectroscopy to assess calf muscle oxidative metabolism in six patients from two unrelated families carrying the c.2708‐2711delTTAG deletion in exon 27 of the OPA1 gene. The rate of postexercise phosphocreatine resynthesis, a measure of mitochondrial adenosine triphosphate production rate, was significantly delayed in the patients. Our in vivo results show for the first time to our knowledge a deficit of oxidative phosphorylation in OPA1‐related DOA. Ann Neurol 2004;56:719–723

Deficient energy metabolism is associated with low free magnesium in the brains of patients with migraine and cluster headache

We used phosphorus magnetic resonance spectroscopy to assess in vivo the brain cytosolic free magnesium concentration and the free energy released by the reaction of adenosine triphosphate (ATP) hydrolysis (DeltaG(ATPhyd)), the latter being an index of the cells bioenergetics condition. We studied 78 patients with migraine in attack-free periods (7 with migraine stroke, 13 with migraine with prolonged aura, 37 with migraine with typical aura or basilar migraine, and 21 with migraine without aura), and 13 patients with cluster headache. In the occipital lobes of all subgroups of migraine and in cluster headache patients cytosolic free [Mg(2+)] as well as the free energy released by the reaction of ATP hydrolysis were significantly reduced. Among migraine patients, the level of free energy released by the reaction of ATP hydrolysis and the cytosolic free [Mg(2+)] showed a trend in keeping with the severity of clinical phenotype, both showing the lowest values in patients with migraine stroke and the highest in patients with migraine without aura. These results support our current hypothesis that the reduction in free [Mg(2+)] in tissues with mitochondrial dysfunction is secondary to the bioenergetics deficit, and are against a primary role of low brain cytosolic free [Mg(2+)] in causing the bioenergetics deficit in headache.

Assessment of glutamate and glutamine contribution to in vivo N‐acetylaspartate quantification in human brain by 1H‐magnetic resonance spectroscopy

N‐Acetylaspartate (NAA) is one of the most important metabolites detectable by brain 1H‐MRS being considered an index of neuronal integrity. At the low magnetic field used in most clinical settings β,γ‐glutamate/glutamine (Glx) resonances are very close and partially overlap the methyl‐NAA resonance interfering with NAA quantification especially at low TE and in the presence of increased Glx signals. NAA overestimation due to Glx on a set of model solutions containing NAA, glutamate, and glutamine in variable amounts was evaluated and the result tested in vivo in six healthy controls and five age‐ and sex‐matched patients with hepatic encephalopathy (HE), the latter having an increased Glx content. A method to assess in vivo the NAA overestimation caused by Glx is proposed. A perfect match was obtained between the assessment of Glx contamination on the NAA of healthy controls and that obtained on the model solutions. However, a substantial difference in NAA overestimation was found between controls and HE patients that cannot be explained by our model. An interpretative hypothesis is provided. Magn Reson Med, 2005.

Abnormal brain energy metabolism shown by in vivo phosphorus magnetic resonance spectroscopy in patients with chronic liver disease

We used phosphorus magnetic resonance spectroscopy (31P-MRS) to assess in vivo the brain bioenergetics of 28 patients with liver cirrhosis. Seven had clinical hepatic encephalopathy (HE), nine hepatocellular carcinoma. 31P-MRS was performed by the DRESS localisation technique on occipital lobes. Brain phosphocreatine was significantly reduced in patients with or without overt HE, and inorganic phosphate was increased in both groups of patients. The cytosolic phosphorylation potential (PP), the relative rate of oxidative metabolism and the regulatory [ADP] were all abnormal. Brain PP was inversely correlated with serum ammonia concentration only in patients without liver cancer. The degree of bioenergetic failure was significantly higher in the presence of overt encephalopathy. We conclude that patients with liver cirrhosis had a derangement of brain energy metabolism, and that 31P-MRS offers a non-invasive method for investigating the underlying mechanisms of HE, with relevant implications in the identification and management of this condition.

Versatile coil design and positioning of transverse-field RF surface coils for clinical 1.5-T MRI applications

Clinical MRI/MRS applications require radio frequency (RF) surface coils positioned at an arbitrary angle α with respect to B0. In these experimental conditions the standard circular loop (CL) coil, producing an axial RF field, shows a large signal loss in the central region of interest (ROI). We demonstrate that transverse-field figure-of-eight (FO8) RF surface coils design are not subject to the same amount of signal loss in the central ROI as loop coils when their orientations are changed. The 1.5-T CL and FO8 prototypes (diameter = 10 cm) were built on Plexiglas using copper strips (width = 4 mm, thickness = 100 μm). The two linear elements of the FO8 coil were 1 cm apart. Axial spoiled gradient echo (SPGR) images of a phantom containing doped water were acquired with the coil plane at α=0°, 45°, and 90°. As α increases, the CL images show, in the central ROI, a signal that decreases from a maximum value to zero. Whereas the FO8 images show, in the same ROI, a signal that varies little from the maximum value (20%). Optimized FO8 coils can be oriented with the coil plane positioned along any direction with respect to B0 without significant signal loss. Transverse RF coil design should be useful for clinical MRS studies and also for parallel imaging techniques where versatile RF coils disposed along arbitrary directions are required.

Improved 1.5 T Magnetic Resonance Spectroscopy in the Human Calf with a Spatially Selective Radio Frequency Surface Coil

We describe the use of a transverse field RF surface coil that improves 1.5 T proton MR spectroscopy in the human calf. A 2-element figure-of-eight (FO8) transverse field RF surface coil (diameter 2R=10 cm; separation between the two linear current elements 2s=1cm) and a circular loop (CL) coil of equal diameter where built and tested with proton PRESS spectra at 1.5 T. The 1 H PRESS spectra obtained in the resting calf muscle of healthy volunteers showed that the FO8 coil allows a higher PRESS SNR (up to a factor 4.5) within a region of about 20 mm centred at about 12 mm from the coil plane, as compared to a standard CL coil. We found also a faster PRESS SNR decrease in the muscle tissue for anterior/posterior distance >20 mm using the FO8 coil. The measured PRESS SNR in the fat tissues of the calf showed a signal mostly localised within 10 mm from the coils surface and with an improved SNR (up to 5.5 times) observed in the presence of the FO8 coil as compared to the CL coil of equal diameter. The FO8 coil design can be advantageous for MRS applications, since it allows higher SNR from a small VOI positioned centrally within a relatively narrow region at a given depth in the human calf. The reported spatial SNR features of the FO8 coil design should also be useful for 1 H and 31 P MRS metabolites quantification in the human brain.