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M Inglese

Publications and source records attributed to M Inglese.

At least 19 recordsLinked to original sources

Field, coil, and echo-time influence on sensitivity and reproducibility of brain proton MR spectroscopy.

BACKGROUND AND PURPOSE: Clinical MR imaging scanners now offer many choices of hardware configurations that were not available in the first 25 years of their existence. Our goal was to assess the influence of coil technology, magnetic field strength, and echo time (TE) on the sensitivity, reflected by the signal intensity-to-noise-ratio (SNR) and reproducibility of proton MR spectroscopy (1H-MR spectroscopy). MATERIAL AND METHODS: The SNR, the intersubject reproducibility, and the intrasubject reproducibility of N-acetylaspartate (NAA), creatine (Cr), and choline (Cho) levels were compared at the common TEs of 30, 144, and 288 ms, by using 1H-MR spectroscopy in 6 volunteers at (1) 3T with a single-element quadrature (SEQ); (2) 1.5T with SEQ; and (3) 1.5T with a 12-channel phased-array (PA) head coil. RESULTS: In terms of sensitivity, the best SNR for all metabolites was obtained at the shortest TE (30 ms). It was comparable between the 3 and 1.5T with the PA, but approximately 35% better than the 1.5T with SEQ. This SNR difference declined <25% at TE of 144 ms and to equity among all imagers at TE of 288 ms. Reproducibility, reflected in the coefficient of variation (CV), was best for NAA at TE of 288 ms, 15%-50% better than at TE of 30 ms in either gray (GM) or white matter (WM). The CV for Cr was best, at TE of 288 ms for GM, but its WM results were independent of TE. Metabolite level reproducibility did not depend on coil technology or magnetic field strength. CONCLUSIONS: For the same coil type, the SNR of all major metabolites was approximately 35% better at 3T than at 1.5T. This advantage, however, was offset at 1.5T with a PA coil, making it a cost-effective upgrade for existing scanners. Surprisingly and counterintuitively, despite the lowest SNR, the best reproducibility was obtained at the longest TE (288 ms), regardless of field or coil.

Adult↗

Intense immunosuppression followed by autologous stem cell transplantation in severe multiple sclerosis.

Aggressive forms of multiple sclerosis (MS) represent a limited group of demyelinating diseases that rapidly progress to severe disability. Currently available therapies are poorly effective against these clinical entities. Recently, it has been demonstrated that intense immunosuppression followed by autologous haematopoietic stem cell transplantation (AHSCT) can affect the clinical course of individuals with severe MS and completely abrogate the inflammatory activity detected by MRI. We report the result of the Italian phase 2 GITMO study, a multicentre study in which 21 MS patients, who were rapidly deteriorating and not responding to the usual therapeutic strategies, were treated with this procedure. The clinical effect of the treatment is long lasting, with a striking abrogation of inflammation detected by MRI findings. These results support a role for intense immunosuppression followed by ASCT as treatment in rapidly evolving MS cases unresponsive to conventional therapies.

Adult↗

Three-dimensional proton spectroscopy of deep gray matter nuclei in relapsing-remitting MS.

The metabolic changes in the deep gray matter (GM) nuclei, thalamus, and basal ganglia of patients with relapsing-remitting multiple sclerosis were investigated with quantitative, multivoxel, three-dimensional proton MR spectroscopy. This technique facilitated the study of several bilateral structures in a single session at sub-cubic centimeter spatial resolution. Compared with 9 matched control subjects, the deep GM nuclei of 11 patients showed 7% lower N-acetylaspartate and 14% higher choline levels (p = 0.02 for both).

Adult↗

Neuronal cell injury precedes brain atrophy in multiple sclerosis.

Global brain atrophy estimated using MRI and whole brain N-acetylaspartate (WBNAA) concentration measured with proton MR spectroscopy were obtained in 42 patients with relapsing-remitting multiple sclerosis and 41 matched control subjects. Patients exhibited cross-sectional atrophy (0.5%; p = 0.033) and WBNAA decline (1.8%/y; p = 0.005) vs disease duration. The 3.6-fold rate disparity between the two processes suggests that neuronal/axonal dysfunction (N-acetylaspartate decline) precedes parenchyma loss, not its consequence (i.e., is an earlier, more sensitive specific metric of the ongoing disease activity).

Adult↗

Brain tissue loss occurs after suppression of enhancement in patients with multiple sclerosis treated with autologous haematopoietic stem cell transplantation.

To assess whether brain tissue loss occurs after profound and sustained suppression of magnetic resonance imaging (MRI) enhancement, we measured brain volume changes from 10 patients with rapidly evolving secondary progressive multiple sclerosis (MS) treated with autologous haematopoietic stem cell transplantation and followed up for 24 months. An average yearly decrease of brain volume of about 1.9% was observed despite only five enhancing lesions seen on triple dose follow up scans of two patients. This indicates that, in MS, progressive loss of tissue can occur independently of concomitant MRI-visible inflammation.

Artifacts↗

The effect of interferon beta-1b on quantities derived from MT MRI in secondary progressive MS.

BACKGROUND: Magnetization transfer (MT) MRI can provide in vivo markers reflecting the severity of irreversible, MS-related brain damage occurring within and outside T2-visible lesions. OBJECTIVE: To assess the effect of interferon (IFN) beta-1b treatment on the accumulation of brain damage in patients with secondary progressive (SP) MS, measured using MT MRI. METHODS: Eighty-two patients with SPMS from five centers participating in a European, multicenter, double-blind, placebo-controlled trial of IFNbeta-1b in SPMS underwent brain T2-weighted and MT MRI at baseline. Evaluable follow-up data were available for 75 patients at 12 months, 54 at 24 months, and 47 at 36 months. MT MRI scans were postprocessed and analyzed to obtain histograms of MT ratio (MTR) values from the whole brain. A region of interest-based analysis of MTR values from the normal-appearing white matter (NAWM) was also performed. RESULTS: In both the treatment arms, there was a decrease of average brain MTR values from baseline to month 24 (mean change -4.9%) and month 36 (mean change -4.3%). These changes were significant for the placebo group at both timepoints and for the IFNbeta-1b group at month 24 only, with no significant treatment effect. A decrease of NAWM MTR was also observed, with no significant difference between the two treatment arms. CONCLUSION: In this cohort of patients with secondary progressive MS, interferon beta-1b did not show an overall effect on the worsening of magnetization transfer MRI measures, when compared with placebo. The data show that change in magnetization transfer ratio is a promising tool for monitoring disease evolution in secondary progressive MS and that the information obtained from magnetization transfer MRI complements that obtained from MRI measures of lesion load and inflammation.

Adult↗

A diffusion tensor magnetic resonance imaging study of brain tissue from patients with migraine.

OBJECTIVE: To measure in vivo, using diffusion tensor magnetic resonance imaging (DT-MRI) the extent of pathological damage of normal appearing brain tissue (NABT) from patients with migraine. METHODS: Dual echo and DT-MRI scans of the brain were acquired from 34 patients with migraine and 17 sex and age matched healthy volunteers. Mean diffusivity (MD) and fractional anisotropy (FA) histograms of the NABT were obtained from all subjects and the histograms' peak heights and average NABT MD and FA measured. When present, average MD and FA values of T2 visible lesions were also measured. RESULTS: In comparison with healthy volunteers, patients with migraine had lower MD histogram peak height (p=0.02) of the NABT. No differences were found in FA histogram derived metrics between migraine patients and healthy subjects. No difference was found for any MD and FA histogram derived metrics between migraine patients with and without brain MRI lesions, and between patients with and without aura. CONCLUSIONS: This study shows that, although brain damage may extend beyond T2 weighted abnormalities in patients with migraine, the severity of these "occult" changes is mild compared with that found in other diseases associated with white matter abnormality.

Adolescent↗

Defective gp130-mediated signal transducer and activator of transcription (STAT) signaling results in degenerative joint disease, gastrointestinal ulceration, and failure of uterine implantation.

The receptor subunit gp130 transduces multiple cell type-specific activities of the leukemia inhibitory factor (LIF)/interleukin (IL)-6 family of cytokines through the signal transducer and activator of transcription (STAT) and src homology 2 domain-bearing protein tyrosine phosphatase (SHP)-2/ras/Erk pathways. To define STAT-dependent physiological responses, we generated mice with a COOH-terminal gp130(DeltaSTAT) "knock-in" mutation which deleted all STAT-binding sites. gp130(DeltaSTAT) mice phenocopyed mice deficient for IL-6 (impaired humoral and mucosal immune and hepatic acute phase responses) and LIF (failure of blastocyst implantation). However, unlike mice with null mutations in any of the components in the gp130 signaling pathway, gp130(DeltaSTAT) mice also displayed gastrointestinal ulceration and a severe joint disease with features of chronic synovitis, cartilaginous metaplasia, and degradation of the articular cartilage. Mitogenic hyperresponsiveness of synovial cells to the LIF/IL-6 family of cyto-kines was caused by sustained gp130-mediated SHP-2/ras/Erk activation due to impaired STAT-mediated induction of suppressor of cytokine signaling (SOCS) proteins which normally limits gp130 signaling. Therefore, the joint pathology in gp130(DeltaSTAT) mice is likely to arise from the disturbance of the otherwise balanced activation of the SHP-2/ras/Erk and STAT signaling cascades emanating from gp130.

Animals↗

Magnetization transfer and diffusion tensor MR imaging of the optic radiations and calcarine cortex from patients with Leber's hereditary optic neuropathy.

Optic nerve abnormalities are easily detectable in patients with Leber's hereditary optic neuropathy (LHON), using magnetic resonance imaging (MRI). However, the presence of structural changes in the optic radiations and calcarine cortex of these patients is still an unresolved issue. In this study, we obtained magnetization transfer (MT) and diffusion tensor (DT) MRI to investigate the integrity of these structures in patients with LHON. Dual echo, MT- and DT-MRI scans of the brain were obtained from 10 men with LHON and 10 healthy sex- and age-matched controls. After image co-registration, we obtained MT ratio (MTR), average diffusivity (D) and fractional anisotropy (FA) maps. MTR, D and FA values for the white matter of the optic radiations and MTR and D values for the calcarine cortex were obtained using a region of interest (ROI) analysis. No macroscopic abnormalities were detected in any of the scans from LHON patients and controls. No statistically significant differences of MTR, D or FA values were found for any of the regions studied in LHON patients and healthy controls. Our results suggest that, in patients with LHON, the optic radiations and the calcarine cortex are spared from structural damage, both at a macroscopic and a microscopic level.

Adult↗

Autologous hematopoietic stem cell transplantation suppresses Gd-enhanced MRI activity in MS.

BACKGROUND: Autologous hematopoietic stem cell transplantation (ASCT) has been recently utilized with encouraging results in patients with poorly controlled MS. OBJECTIVE: To determine in severe cases of MS the effect of ASCT on gadolinium (Gd)-enhanced MRI and to obtain information on clinical course and safety. METHODS: In a cooperative study, 10 patients with rapidly evolving secondary progressive MS were transplanted, after BEAM conditioning regimen (carmustine, etoposide, cytosine-arabinoside, and melphalan), with unmanipulated autologous peripheral blood SC mobilized with high-dose cyclophosphamide (CY; 4 g/m2) and granulocyte-colony-stimulating factor. Triple-dose Gd-enhanced scans were performed monthly for a pretreatment period of 3 months and compared with serial monthly Gd-enhanced MRI for the following 6 months and then once every 3 months. RESULTS: The median follow-up is now 15 months (range 4 to 30 months). The number of Gd-enhancing lesions decreased immediately after mobilization with CY and finally dropped to zero in all cases after the conditioning regimen. The number of new T2-weighted positive lesions paralleled data obtained for Gd-enhanced MRI. Clinically, patients improved slightly or remained stable. CONCLUSION: These results demonstrate that the therapeutic sequence CY-BEAM-ASCT has the capacity to completely suppress MR-enhancing activity, an effect that is sustained with time. The final impact of this procedure on disease course remains to be established.

Adult↗

Overview of diffusion-weighted magnetic resonance studies in multiple sclerosis.

Diffusion-weighted magnetic resonance imaging (DW-MRI) provides a unique form of MR contrast that enables the diffusional motion of water molecules to be quantitatively measured. As a consequence, DW-MRI provides information about the size, shape, integrity, and orientation of brain structures. Pathological processes able to alter tissue integrity by removing or modifying some of the structural barriers that normally restrict water molecular motion in biological tissues cause changes in water diffusion characteristics, which can be measured in-vivo using DW-MRI. Although DW-MRI has been shown to be of great clinical utility in the assessment of patients with cerebral ischemia, it is also increasingly being used to quantify in-vivo the extent and severity of multiple sclerosis (MS) pathology. The pathological elements of MS have the potential to alter the permeability or geometry of structural barriers to water molecular motion in the brain, optic nerve and spinal cord. The present review outlines the major contributions given by DW-MRI for the quantification of MS-related damage and for the understanding of MS pathophysiology.

Animals↗

Diffusion tensor magnetic resonance imaging in multiple sclerosis.

OBJECTIVES: To quantify, using diffusion tensor imaging (DTI), the tissue damage in lesions and normal-appearing white matter (NAWM) from a large cohort of patients with MS and to investigate the magnitude of the correlation between DTI-derived metrics and clinical disability. METHODS: Dual-echo and DTI scans were obtained from 78 patients with relapsing-remitting, secondary progressive, or primary progressive MS and from 20 normal control participants. Post-contrast T1-weighted images were also obtained from the patients. After creating mean diffusivity (D) and fractional anisotropy (FA) images and image coregistration, D and FA values were measured for 4846 lesions (3207 nonenhancing T1-isointense, 1511 nonenhancing T1-hypointense, and 128 enhancing), 497 NAWM areas from patients, and 160 white matter areas from the controls. RESULTS: The average lesion D was higher and the average lesion FA was lower than the corresponding quantities of the NAWM (p < 0.001). The values of enhancing and nonenhancing lesions were not different, whereas enhancing lesions had lower FA (p < 0.001). T1-hypointense lesions had higher D and lower FA than T1-isointense lesions (p < 0.001). NAWM of patients had higher and lower FA than white matter of controls (p = 0.01). Significant correlations were found between T1 and T2 lesion volume and and FA of lesions and NAWM. In the overall patient sample, a moderate correlation was also found between lesion D and the Expanded Disability Status Scale score (r = 0.28, p = 0.01). However, the r value of this correlation was 0.48 in patients with secondary progressive MS, whose disability was also correlated with average lesion FA (r = -0.50). CONCLUSIONS: The results of this study show that DTI is able to identify MS lesions with severe tissue damage and to detect changes in the NAWM. They also indicate that DTI-derived measures are correlated with clinical disability, especially in patients with secondary progressive MS, thus suggesting a role for DTI in monitoring advanced phases of the disease.

Adult↗

Segmenting brain white matter, gray matter and cerebro-spinal fluid using diffusion tensor-MRI derived indices.

Based on its ability to provide quantitative information about tissue microstructure, diffusion tensor magnetic resonance imaging (DT-MRI) might be a valuable approach to improve the reliability of segmentation of the various brain tissues. In this study, a fully automated and easy-to-implement technique based on 2D histogram analysis of DT-MRI derived images was used to segment white and gray matter of the brain from 10 healthy subjects (aged = 27-56 years). The results obtained with this novel segmentation strategy were compared to those achieved by two experienced observers using an operator-dependent segmentation on the dual-echo scans. Visual inspection of the segmented tissues from a third senior observer disclosed that the automated technique worked properly on all images from all subjects and was more accurate than the human raters in defining thalamus white and gray matter portions as well as in tissue classification at the external brain edge. In addition, this segmentation technique resulted in an average gray/white matter ratio similar to that reported by post-mortem assessment. The application of the operator-dependent segmentation strategy was extremely time-consuming and the two observers achieved poorly reproducible results. Segmenting brain white and gray matter using information from DT-MRI proved to be an accurate approach with the potential for improving the understanding of the pathophysiology of many neurologic conditions.

Anisotropy↗

Magnetic resonance imaging, magnetisation transfer imaging, and diffusion weighted imaging correlates of optic nerve, brain, and cervical cord damage in Leber's hereditary optic neuropathy.

OBJECTIVES: Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease leading to bilateral loss of central vision and severe optic nerve atrophy. A subtype of LHON presents additional clinical and MRI aspects indistinguishable from those of multiple sclerosis (MS) (LHON-MS). In patients with LHON or LHON-MS, an assessment was made of (a) the severity of optic nerve damage, using MRI and magnetisation transfer imaging (MTI), and (b) the presence and extent of macroscopic and microscopic pathology in the brain and cervical cord, using MRI and MT ratio (MTR) and mean diffusivity (D) histogram analysis. METHODS: Ten patients with LHON, four with LHON-MS, and 20 age and sex matched healthy controls were studied. For the optic nerve and the brain, dual-echo turbo spin echo (TSE), T1 weighted spin echo, and MT images were obtained. For the brain, fast fluid attenuated inversion recovery (fast FLAIR) and diffusion weighted images were also obtained. For the cervical cord, fast short tau inversion recovery (STIR) and MT images were obtained. The volume and the average MTR value of both the optic nerves were measured. MTR and histograms of the normal appearing brain tissue (NABT) and MTR histograms of the whole cervical cord tissue were created. RESULTS: The mean values of optic nerve volumes and MTR were significantly lower in patients with LHON than in healthy controls. Mean NABT-MTR histogram peak height was significantly lower in patients with LHON than in controls, whereas no significant difference was found for any of the cervical cord MTR histogram derived measures. Average diffusivity (D) was higher in patients with LHON than in controls. Optic nerve volume and MTR value and mean NABT-MTR were lower in patients with LHON-MS than in those with LHON. CONCLUSIONS: The severity of optic nerve pathology in LHON is measurable in vivo using MRI and MTI. MTR and histogram analysis suggests that microscopic brain damage occurs in LHON and that it is more severe in the MS-like form of the disease.

Adult↗

Scan-rescan variation of measures derived from brain magnetization transfer ratio histograms obtained in healthy volunteers by use of a semi-interleaved magnetization transfer sequence.

SUMMARY: A novel semiinterleaved gradient-echo (GE) sequence for quantitative measurement of magnetization transfer ratio (MTR) is described. With this sequence, several lines of k-space are collected for the non-MT image then several lines are collected for the MT image, thus building up the entire k-space in distinct acquisition blocks, with a good trade-off between motion-induced misregistration and degree of MT effect. The scan-rescan coefficients of variation for several MTR histogram-derived measures from 10 healthy volunteers scanned serially with this semiinterleaved sequence proved to be lower than those achieved using a conventional GE sequence. This sequence may be useful in a clinical environment to measure MTR changes over time more reliably than when acquiring the non-MT and MT images sequentially, which inevitably are affected by patient motion.

Adult↗

Mean diffusivity and fractional anisotropy histograms of patients with multiple sclerosis.

BACKGROUND AND PURPOSE: Compared with conventional T2-weighted MR imaging, diffusion tensor MR imaging provides quantitative indices with increased specificity to the most destructive aspects of multiple sclerosis. In this study, we obtained brain mean diffusivity (_D) and fractional anisotropy histograms of patients with multiple sclerosis to compare them with those of healthy volunteers and to investigate the correlation between diffusion tensor MR imaging histogram-derived measures and the level of disability and quantities derived from conventional MR imaging. METHODS: Dual-echo and diffusion tensor MR images were obtained from 78 patients with relapsing-remitting, secondary progressive, or primary progressive multiple sclerosis and from 20 healthy control volunteers. After obtaining mean diffusivity (_D) and fractional anisotropy images and image coregistration, _D and fractional anisotropy histograms were created. From each histogram, the following measures were derived: the average _D and fractional anisotropy, the histogram peak heights, and the histogram peak locations. RESULTS: All the _D and fractional anisotropy histogram-derived measures were different between patients and controls at a significance level of P <.001. No differences were found in any of the considered quantities among the three multiple sclerosis phenotypes. In patients with relapsing-remitting multiple sclerosis, disability was correlated with histogram average_D (r = 0.4, P =.01) and peak height (r = -0.4, P =.01). In patients with secondary progressive multiple sclerosis, disability was correlated with fractional anisotropy histogram peak position (r = -0.6, P =.01). Significant correlations were also found between T2 lesion load and various diffusion tensor MR quantities. CONCLUSION: This study shows that brain _D and fractional anisotropy histograms are different for patients with multiple sclerosis compared with control volunteers. This study also shows that quantities derived from diffusion tensor MR imaging are correlated with disability in patients with relapsing-remitting multiple sclerosis and secondary progressive multiple sclerosis, suggesting that they might serve as additional measures of outcome when monitoring multiple sclerosis evolution in these patients.

Adult↗

Magnetization transfer imaging to monitor the evolution of MS: a 1-year follow-up study.

OBJECTIVES: To assess the sensitivities of magnetization transfer imaging (MTI)-derived measures in detecting changes over time of macro- and microscopic lesion burdens in different MS phenotypes and to compare them with those of T2-weighted and T1-weighted lesion volumes. METHODS: A total of 96 patients were studied: 39 with relapsing-remitting MS (RRMS), 19 with secondary progressive MS (SPMS), nine with primary progressive MS, and nine with benign MS; 20 with clinically isolated syndromes suggestive of MS at presentation; and 20 healthy subjects. Brain T2-weighted, T1-weighted, and MTI scans were obtained at baseline and after 12 months. The authors measured T2-weighted and T1-weighted lesion volumes and average lesion MT ratio (MTR). The authors also derived MTR histograms from whole brain tissue (WBT) and normal-appearing brain tissue (NABT). RESULTS: In healthy control subjects, there was no significant change of any of the MTR histogram parameters. At follow-up, in the entire patient group, T2-weighted lesion volume significantly increased and average lesion MTR, WBT-MTR, NABT-MTR, and histogram peak positions significantly decreased. Patients with RRMS and SPMS had significantly higher changes in T2-weighted lesion volume and all the MTI-derived metrics compared with the other subgroups. MTI changes were more prominent (and significantly different) in patients with SPMS than in those with RRMS. Compared with patients with benign MS, patients with RRMS had significantly greater changes in T2-weighted lesion volume and WBT- and NABT-MTR metrics. Compared with patients with SPMS, patients with primary progressive MS had similar changes of T1-weighted and T2-weighted lesion volumes, but significantly lower changes of MTI-derived measures. CONCLUSIONS: MTI-derived measures are sensitive for detecting MS-related changes and might provide valuable outcome measures when assessing treatment effects in clinical trials of patients with MS.

Adult↗