Gioacchino Tedeschi

Brain regional distribution pattern of metabolite signal intensities in young adults by proton magnetic resonance spectroscopic imaging

Proton magnetic resonance spectroscopy (1H-MRS) is evolving from single-volume localized acquisitions to multiple-volume acquisitions using magnetic resonance spectroscopic imaging (lH-MRSI). The normal regional patterns of 1H-MRSI-detectable metabolite signal intensities have yet to be established. We studied 13 healthy young adults with a multiple-section lH-MRSI technique. The metabolite signals measured were N-acetylaspartate (NA), cho-line-containing compounds (CHO), creatine-phosphocreatine (CRE), and lactate. Ten neuroanatomic regions (nine bilateral) were identified in gray matter, white matter, and basal nuclei. Analysis of the data led to the following conclusions: (1) NA and CHO signals from centrum semiovale (CSO) can be used as a normalizing factor to reduce intersub-ject variability due to external causes; (2) in normal human brain, there is no left versus right asymmetry in the regions studied; (3) statistically significant patterns of signal distribution of NA, CHO, and CRE can be identified in normal human brain; and (4) CSO-normalized metabolite signal intensities and metabolite ratios complement each other for the detection of significant regional differences.

Proton magnetic resonance spectroscopic imaging in childhood ataxia with diffuse central nervous system hypomyelination

The spatial distribution of metabolite signal intensities can be measured within entire sections of the brain by proton magnetic resonance spectroscopic imaging (1) H-MRSI). A group of six patients (4 unrelated girls and 2 brothers from 5 families) with childhood ataxia with diffuse CNS hypomyelination (CACH) underwent long-echo-time, single-slice1 H-MRSI. Relative to controls, there was a decrease in the signal intensity of N-acetylaspartate, choline, and creatine throughout the white matter in all six patients. We identified lactate signals in white matter in three of them with advanced disease. The degree of white matter involvement was not homogeneous over the entire patient group, but did correlate with clinical presentation. Deep and posterior white matter tended to be more involved. There were no1 H-MRSI abnormalities in the gray matter.1 H-MRSI findings suggest that this syndrome is secondary to a metabolic defect causing hypomyelination, axonal degeneration, and, in the most compromised cases, accumulation of lactate. This study shows that CACH is not limited to girls. NEUROLOGY 1995;45: 1526-1532

Cortical and subcortical chemical pathology in Alzheimer's disease as assessed by multislice proton magnetic resonance spectroscopic imaging

Background: Multislice proton magnetic resonance spectroscopic imaging (1H-MRSI) permits the simultaneous acquisition of N-acetylaspartate (NA), choline (Cho), creatine/phosphocreatine (Cre), and lactate (Lac) signal intensities from four 15-mm slices divided into 0.84-ml single-volume elements. NA is inferred to be a neuron-specific molecule, whereas Cho mainly reflects glycerophosphocholine and phosphocholine, compounds involved in phospholipid metabolism. Objective: To assess whether 1H-MRSI could detect a regional pattern of cortical and subcortical involvement in the brain of Alzheimers disease (AD) patients. Methods: 1H-MRSI was performed in 15 patients with probable AD and 15 age-matched healthy controls. Regions of interest (ROIs) were selected from frontal (FC), temporal (TC), parietal (PC), occipital, and insular cortices, subcortical white matter (WM), and thalamus. Results: In AD patients, we found a significant reduction of NA/Cre in the FC, TC, and PC and a significant reduction of Cho/Cre in the WM. Conclusions: This 1H-MRSI study of AD patients shows a regional pattern of neuronal damage in the associative cortices, as revealed by significant reduction of NA/Cre in the FC, TC, and PC, and regional derangement of phospholipid metabolism, as revealed by significant reduction of Cho/Cre in the WM. NEUROLOGY 1996;47: 696-704

MR image segmentation and tissue metabolite contrast in 1H spectroscopic imaging of normal and aging brain.

The impact of image segmentation on 0.84‐ml nominal voxel volume proton spectroscopic imaging in normal brain and in age‐related cortical atrophy was investigated. Segmentation improved the gray matter‐white matter (GM‐WM) contrast for N‐acetyl aspartate (NAA)/creatine (Cr) and choline (Cho)/Cr in normal brain, and for NAA/Cho and NAA/Cr in atrophic brain. NAAGM/WM (∼0.7), ChoGM/WM (∼0.8), and CrGM/WM (∼1.3) in normal brain obtained with segmentation agreed with values obtained with quantitative magnetic resonance spectroscopy. Age‐related cortical atrophy led to decreased cortical GM NAA/Cho and NAA/Cr; no changes were evident in WM or in NAAGM/WM, ChoGM/WM, or CrGM/WM. GM/WM metabolite analysis may be of limited use in conditions in which parallel metabolite changes occur in WM and GM.u2003Magn Reson Med 41:841–845, 1999.u2003Published 1999 Wiley‐Liss, Inc.

Diffuse central neuronal involvement in Fabry disease: A proton MRS imaging study

Background: The in vivo determination of parenchymal involvement is important to evaluate disease burden. Proton MRS imaging (1H-MRSI) permits simultaneous measurement of N-acetylaspartate (NA), a putative neuron-specific molecule, choline-containing compounds, creatine-phosphocreatine, and lactate from four 15-mm slices divided into 0.84-mL single-volume elements. Objective: To assess the cortical and subcortical neuropathology in Fabry disease (FD). Methods: Regions of interest (ROIs) were selected from several cortical and subcortical locations in nine FD patients. Mean ROI metabolite ratios were compared with control values. Results: FD patients showed a widespread pattern of cortical and subcortical NA reduction. Seven patients showed discrete MRI abnormalities consisting of white matter hyperintensities or basal ganglia infarcts. Conclusion: We found diffuse neuronal involvement in FD extending beyond the areas of MRI-visible cerebrovascular abnormalities. 1H-MRSI may become useful in therapeutic trials.

Spectroscopic imaging of radiation-induced effects in the white matter of glioma patients

External radiation therapy of brain tumors may cause adverse effects on normal brain tissue, resulting in severe neuropsychological and cognitive impairment. We investigated the late delayed radiation effects in the white matter (WM) using (1)H magnetic resonance spectroscopic imaging ((1)HMRSI). Nine glioma patients with local radiation-induced signal abnormalities in the T(2)-weighted MR images were studied with nine age- and sex-matched controls. The metabolite ratios in the radiation-induced hyper intensity area (RIHA) and in the normal appearing white matter (NAWM) of the patients were compared with respective WM areas of the controls. In RIHA, choline/creatine (Cho/Cr) was 17% decreased (1.22 +/- 0.13 vs 1.47 +/- 0.16, p = 0.0027, significant (s), unpaired Students t test with Bonferroni correction) in the patients compared to the controls, while there was no difference in N-acetyl aspartate/Cr (NAA/Cr) (2.49 +/- 0.57 vs 2.98 +/- 0.32, p = 0.039) or NAA/Cho (2. 03 +/- 0.40 vs 2.04 +/- 0.17, p = 0.95). In NAWM, Cho/Cr was 24% decreased (1.21 +/- 0.15 vs 1.59 +/- 0.13, p < 0.0001, s) and NAA/Cho was 20% increased (2.49 +/- 0.49 vs 1.98 +/- 0.15, p = 0. 0082, s) in the patients compared to the controls, while there was no difference in NAA/Cr (2.99 +/- 0.46 vs 3.16 +/- 0.32, p = 0.38). NAA(RIHA)/NAA(NAWM) was 25% decreased (0.75 +/- 0.20 vs 1.00 +/- 0. 12, p = 0.0043, s) and Cr(RIHA)/Cr(NAWM) was 16% decreased (0.89 +/- 0.15 vs 1.06 +/- 0.10, p = 0.013, s) in the patients compared to the controls, while there was no difference in Cho(RIHA)/Cho(NAWM) (0.92 +/- 0.23 vs 0.98 +/- 0.10, p = 0.47). (1)HMRSI reveals widespread chemical changes in the WM after radiation therapy. In RIHA, there is loss of NAA, Cho, and Cr implying axonal and membrane damage and in NAWM, there is loss of Cho, reflecting membrane damage.

Diffuse neuroaxonal involvement in mucolipidosis IV as assessed by proton magnetic resonance spectroscopic imaging

Mucolipidosis IV is an autosomal recessive disorder caused by mutations in MCOLN1, which codes for mucolipin, a transient receptor potential protein. In order to investigate brain metabolic abnormalities in mucolipidosis IV, we studied 14 patients (11 children, 3 adults) by proton magnetic resonance spectroscopic imaging. The ratios of N-acetylaspartate/ creatine-phosphocreatine and N-acetylaspartate/choline-containing compounds in patients with mucolipidosis IV were significantly reduced in all regions of interest except the parietal gray matter and thalamus. The ratios of choline-containing compounds/creatine-phosphocreatine was not significantly reduced in patients compared with controls. The ratio of N-acetylaspartate/creatine-phosphocreatine were significantly lower (P = .005) in the more neurologically impaired patients compared with the least impaired. For every region of interest, except for parietal gray matter, the ratio of N-acetylaspartate/creatine-phosphocreatine was lower in the more motorically impaired patient group. There was no difference for the ratio of N-acetylaspartate/creatine-phosphocreatine between younger and older patients. These findings suggest that mucolipidosis IV is largely a static developmental encephalopathy associated with diffuse neuronal and axonal damage or dysfunction. Mucolipin deficiency impairs motor more than sensory central nervous system pathways. (J Child Neurol 2003;18:443—449).

La terapia della sclerosi multipla

Allo stato attuale non esiste alcuna terapia in grado di guarire la sclerosi multipla (SM), ma le terapie a nostra disposizione permettono, a seconda della fase della malattia e del suo decorso, di trattare efficacemente l’episodio acuto, ridurre la frequenza delle ricadute e, parzialmente, la disabilita e di migliorare alcuni sintomi. Globalmente, pertanto, siamo in grado di modificare il decorso della malattia.

The Diagnosis of Multiple Sclerosis

The diagnosis of Multiple Sclerosis (MS) is based on a careful evaluation of clinical history, on neurological exam and paraclinical tests aimed at identifying temporal and spatial dissemination of demyelinating lesions of the Central Nervous System; on the other side, it is mandatory to exclude any other possible disease able to better explain clinical symptoms. In 2001 diagnostic criteria revised in 2005 and more recently in 2010 have been elaborated to define clinical and paraclinical evidences necessary for the diagnosis of MS; instrumental exams include Magnetic Resonance Imaging (MRI), cerebrospinal fluid analysis and visual evoked potentials. MRI is necessary to demonstrate dissemination in time and space of demyelinating lesions.