Biomedical subjects

M A Rocca

Publications and source records attributed to M A Rocca.

At least 19 recordsLinked to original sources

PubMed2000

Pathologic damage in MS assessed by diffusion-weighted and magnetization transfer MRI.

OBJECTIVE: To compare diffusion characteristics of MS lesions, normal-appearing white matter (NAWM) from patients, and normal white matter from control subjects, and to investigate the correlations between the magnetization transfer ratio (MTR) and a directionally averaged tissue water diffusion coefficient (D) in patients. BACKGROUND: MS and other pathologic processes that modify tissue integrity can result in abnormal diffusion of water molecules detectable by diffusion-weighted imaging (DWI). METHODS: Conventional dual-echo and DWI scans were obtained from 35 patients with relapsing-remitting MS and 24 healthy control subjects. MT scans were also obtained from the patients. After coregistration of all scans, MTR and D values from MS lesions and NAWM in different regions were marked using the dual-echo scans as a reference. D values from the same brain regions in control subjects were acquired. Histograms of MTR and D were also produced. RESULTS: Patients with MS had significantly higher D values in all the areas studied. Moreover, histogram metrics (peak height, peak site, and average D) from patients were substantially different from those of control subjects. In patients, average lesion D and MTR were markedly different from those in the NAWM. There was an inverse correlation between average lesion MTR and D inside lesions, whereas no correlation was found for average MTR and D taken from the histograms. CONCLUSIONS: DWI detects severe tissue disruption inside lesions and subtle widespread abnormalities in NAWM in patients with relapsing-remitting MS. MT and DWI may provide information about different aspects of brain pathology in MS.

Adult↗

PubMed2000

A magnetization transfer imaging study of the brain in patients with migraine.

The authors evaluated the magnetization transfer ratio (MTR) of T2 lesions, normal-appearing white matter (NAWM), and brain from 39 migraineurs, 17 healthy volunteers, and 22 patients with MS. Migraineurs had NAWM and brain MTR values similar to those of normal subjects but significantly higher than those of MS patients. Average lesion MTR values also were significantly lower in MS patients than in migraineurs. In patients with migraine, other etiologies should be considered in the presence of tissue damage beyond that seen on T2-weighted scans.

Adolescent↗

PubMed2000

A conventional and magnetization transfer MRI study of the cervical cord in patients with MS.

OBJECTIVE: To evaluate the contribution made by cervical cord damage, assessed using a fast short-tau inversion recovery (fast-STIR) sequence and magnetization transfer ratio (MTR) histogram analysis to the clinical manifestations of MS. BACKGROUND: Previous studies have failed to show significant correlations between the number and extent of T2 spinal cord lesions and the clinical status of patients with MS. Fast-STIR is more sensitive than T2-weighted imaging for detecting cervical cord MS lesions. MTR histogram analysis provides estimates of the overall disease burden in the cervical cord with higher pathologic specificity to the more destructive aspects of MS than T2-weighted scans. METHODS: We obtained fast-STIR and magnetization transfer (MT) scans from 96 patients with MS (52 with relapsing-remitting [RRMS], 33 with secondary progressive [SPMS], and 11 with primary progressive [PPMS] MS) and 21 control subjects. Dual-echo scans of the brain were also obtained and lesion load measured. RESULTS: Eighty-one of the patients with MS had an abnormal cervical cord scan. Patients with SPMS had more cervical cord lesions and more images with visible cervical cord damage than did patients with RRMS or PPMS (p = 0.04). The entire cohort of patients with MS had lower average MTR of the cervical cord (p = 0.006) than control subjects. Compared to control subjects, patients with RRMS had similar cervical cord MTR histogram-derived measures, whereas those with PPMS had lower average MTR (p = 0.01) and peak height (p = 0.02). Patients with SPMS had lower histogram peak height than did those with RRMS (p = 0.03). The peak position and height of the cervical cord MTR histogram were independent predictors of the probability of having locomotor disability. We found no correlation between brain T2 lesion load and any of the cervical cord MTR histogram metrics. CONCLUSIONS: This study shows that the amount and severity of MS pathology in the cervical cord are greater in the progressive forms of the disease. An accurate assessment of cervical cord damage in MS gives information that can be used in part to explain the clinical manifestations of the disease.

Adult↗

PubMed2000

Activity revealed in MRI of multiple sclerosis without contrast agent. A preliminary report.

Disease activity in multiple sclerosis is usually accompanied by blood-brain barrier disruption, which can be assessed with contrast-enhanced magnetic resonance imaging (MRI). This paper describes a technique that gives information about disease activity using magnetization transfer MRI. Image combination methods using follow-up scans, like the one presented here, have the potential to show MS lesions that correlate with enhancement.

Blood-Brain Barrier↗

PubMed2000

Reproducibility of magnetization transfer ratio histogram-derived measures of the brain in healthy volunteers.

Using two MR scanners, we evaluated the intraobserver, interobserver, image-reimage, and interimager variabilities in the assessment of magnetization transfer ratio (MTR) histograms obtained monthly on four occasions from five healthy volunteers. With multiple observers, the mean coefficients of variations ranged from 2.2% to 8.2% for "pure" image-reimage variability, from 1.2% to 4.9% for interobserver variability, and from 2.1% to 4.9% for image-reimage variability. The mean intraobserver coefficients of variations were always lower than 1%. The mean coefficients of variations ranged from 10.2% to 14.6% for pure interimager variability and from 8.6% to 14.3% for interimager variability with multiple observers. Interimager variability accounted for 96.0% of the overall variability of average MTR, for 96.7% of peak location, and for 41.1% of the peak height. The use of different MR scanners is the main source of variability when obtaining MTR histograms.

Adult↗

PubMed1999

A multiparametric MRI study of frontal lobe dementia in multiple sclerosis.

Previous studies achieved conflicting results when correlating magnetic resonance imaging (MRI) abnormalities and cognitive impairment in multiple sclerosis (MS) patients. Recently, the estimation of MS lesion load on T1-weighted images and the analysis of magnetization transfer ratio (MTR) histograms, increased the degree of the correlation between physical disability and MRI findings in MS. We assessed the relationship of conventional and non-conventional MRI-derived measures with frontal lobe dementia in MS. Dual echo, T1-weighted and MT MRI scans of the brain were obtained in 11 MS patients with and in 11 without frontal lobe dementia, matched for age, sex, education and disability. Total (TLL) and frontal (FLL) lesion loads were assessed from T2- and T1-weighted scans. MTR histogram analysis was performed for the whole brain, the frontal lobe and the cerebellum. Median TLL and FLL were significantly higher in cognitively impaired patients on both T2- and T1-weighted scans. The MRI measure that better discriminated the two groups of patients was T1-weighted TLL (median values were 19.1 ml for demented and 1.9 ml for non-demented patients, P=0.006). Average MTR, peak height and location of overall brain and frontal lobe histograms were significantly lower for cognitively impaired than for cognitively intact patients (P values ranged from 0.0001 to 0.001). Cerebellar MTR histogram metrics did not significantly differ in patients with and without cognitive decline. The presence of cognitive decline in MS is associated with the extent and pathological severity of brain MRI abnormalities.

Dementia↗

PubMed1999

MRI and magnetization transfer imaging changes in the brain and cervical cord of patients with Devic's neuromyelitis optica.

OBJECTIVES: To assess MRI and magnetization transfer (MT) imaging changes in the brain and cervical cord from patients with Devic's neuromyelitis optica (DNO), and to compare them with those from patients with MS. BACKGROUND: In MS, MT imaging detects changes within the normal-appearing brain tissue (NABT). MS lesions in the cord usually are isointense on T1-weighted images. No study has investigated these two aspects in patients with DNO. METHODS: The authors obtained dual echo, fast fluid-attenuated inversion recovery, T1-weighted, and MT scans of the brain from 8 DNO patients, 10 MS patients, and 9 healthy volunteers. T2-weighted, short-tau inversion recovery, T1-weighted, and MT scans of the cervical cord also were obtained. The authors identified lesions visible on the different scans and quantified the volumes for those in the brain. MT ratio (MTR) histogram analysis of the NABT and of the entire cervical cord also was performed. RESULTS: No brain abnormalities were found on the T2-weighted scans from healthy volunteers and from seven DNO patients. No significant difference was found for any of the NABT-MTR histogram metrics between DNO patients and controls, whereas MS patients had a significantly lower histogram average MTR and peak height. No abnormalities were seen on any of the scans of the cervical cord from healthy volunteers. All DNO patients had a single lesion longer than two vertebral segments. Five of them were hypointense on T1-weighted scans. The authors identified 24 cord lesions from MS patients: 22 were shorter than two vertebral segments and none was hypointense. There was no difference in cervical cord MTR histogram metrics between DNO and MS patients. CONCLUSIONS: This study demonstrates that patients with Devic's neuromyelitis optica (DNO) and MS have different imaging characteristics of the brain and cervical cord. This provides further evidence that DNO is a clinical entity separate from MS.

Adult↗

PubMed1999

Magnetization transfer imaging of patients with definite MS and negative conventional MRI.

OBJECTIVE: To assess, in a group of patients with clinically or laboratory-supported definite MS and negative conventional MRI scans of the brain, whether magnetization transfer imaging (MTI) is able to detect subtle white matter changes. BACKGROUND: MTI of the brain in patients with MS frequently demonstrates the presence of microscopic damage to white matter, which appears normal on conventional MRI. METHODS: Brain MRI and MTI scans were obtained from 11 patients with negative conventional MRIs of the brain, selected from 618 clinically or laboratory-supported definite MS cases scanned in the last 2 years in three Italian MS centers. RESULTS: Compared with control subjects, patients had significantly lower mean MT ratios (MTR) in the pons, cerebellum, and periventricular regions. The percentages of pixels with MTR values below 1, 2, and 3 SD of the mean MTR value of the control subjects were 7.6% (range, 3.2% to 11.8%), 5.2% (range, 2.0% to 8.5%), and 3.6% (range, 1.2% to 6.1%), respectively. They were mainly located in the white matter of the centra semiovalia, and usually were isolated. CONCLUSIONS: MTI can detect white matter abnormalities in patients with MS and negative conventional brain MRI scans. The detection of such abnormalities may increase diagnostic confidence in those cases where MS is clinically suspected, but conventional MRI does not suggest the diagnosis.

Adolescent↗

PubMed1999

Disease activity in multiple sclerosis studied by weekly triple-dose magnetic resonance imaging.

This study assessed whether dysfunction of the blood-brain barrier is an obligatory early event in lesion formation in multiple sclerosis. Dual-echo and T1-weighted magnetic resonance imaging after the injection of a triple dose (0.3 mmol/kg) of gadolinium-DTPA were obtained from ten patients with relapsing-remitting multiple sclerosis every week for 2 months. Sixty-four newly active lesions were detected by the two techniques. All the 44 new lesions seen on dual-echo scans enhanced during the early phases of their formation: 33 at their first appearance, 10 1 week before their appearance on the dual-echo scans, and one the week thereafter. When the every fourth (monthly) scan was analyzed, a total of 55 newly active lesions were detected (i.e., 14% active lesions would have been missed compared to the number found on weekly scanning). Thirty-one of them were detected by both dual-echo and triple-dose scans, 15 only by enhanced scans, and nine only by dual-echo scans. This study confirms that with highly sensitive magnetic resonance imaging techniques dysfunction of the blood-brain barrier is an obligatory early event in new lesion formation in relapsing-remitting multiple sclerosis.

Adult↗

PubMed1999

Lesion load measurements in multiple sclerosis: the effect of incorporating magnetization transfer contrast in fast-FLAIR sequence.

We compared the ability and reproducibility of a fast fluid-attenuated inversion recovery (fast-FLAIR) sequence with and without a magnetization transfer (MT) pulse for detecting and measuring multiple sclerosis (MS)-related abnormalities on magnetic resonance imaging (MRI) scans from 20 patients. The Contrast-to-Noise ratios between lesions and normal-appearing white matter, lesion numbers, lesion volumes and the variability of such measurements were similar for the two sequences. This suggests that the addition of MT to FLAIR sequences as currently implemented on standard MRI scanners does not improve the detection of MS lesions.

Adult↗

PubMed1999

Short-term evolution of individual enhancing MS lesions studied with magnetization transfer imaging.

We performed serial monthly magnetization transfer (MT) imaging to evaluate the prevalence and evolution of structural changes in individual enhancing lesions from patients with multiple sclerosis (MS). Every 4 weeks for 3 months, we obtained dual echo, magnetization transfer (MT) imaging and, 5 min after SD (0.1 mmol/kg) gadolinium-DTPA injection, T1-weighted scans from 10 patients with early relapsing-remitting MS. We measured the MT ratio (MTR) of enhancing lesions seen on the entry scans on co-registered quantitative MTR images at entry and during the follow up. Fourty-two enhancing lesions were identified on the entry scans. According to the "maximal random fluctuation" detected for the normal-appearing white matter MTR values, 16 (38%) lesions were classified as "increasing MTR" lesions, 21 (50%) as "stable MTR" lesions, and 5 (12%) as "decreasing MTR" lesions. The classification of the lesions after the first month of follow up strongly predicted the classification at the end of the follow up (chi squared = 20.35, p = 0.0004). These results indicate that the enhancing lesion population in MS is heterogeneous, and that reparative mechanisms occurring after blood-brain barrier opening are not efficient in only a minority of the enhancing lesions from patients with early relapsing-remitting MS.

Adult↗

PubMed1999

Lesion load quantification on fast-FLAIR, rapid acquisition relaxation-enhanced, and gradient spin echo brain MRI scans from multiple sclerosis patients.

Previous studies have addressed the issue of the usefullness of fast fluid-attenuated (fast-FLAIR), rapid acquisition relaxation-enhanced (RARE), and gradient spin echo (GRASE) sequences in small groups of patients with multiple sclerosis (MS). The aim of this study was to assess and compare the lesion volumes and the intra-rater reproducibility of such measurements using fast-FLAIR, dual echo RARE, and dual echo GRASE brain scans from a large sample of MS patients. Using a 1.5 Tesla scanner, fast-FLAIR, dual echo RARE, and dual echo GRASE scans (24 axial, 5-mm thick contiguous interleaved slices) of the brain were obtained from 50 MS patients. Total lesion loads (TLL) were assessed twice using a semi-automated local thresholding segmentation technique by the same rater from the scans obtained with the three techniques. Mean TLL were 20.3 mL for fast-FLAIR, 16.6 mL for RARE, and 17.6 mL for GRASE sequences. Mean TLL detected by the three techniques were significantly heterogeneous (p < 0.001); at post-hoc analysis, the mean lesion volume detected on fast-FLAIR images was significantly higher than that on both RARE and GRASE images (p < 0.001) and the mean TLL on GRASE scans was significantly higher than that on RARE scans (p = 0.001). The mean values of intra-observer coefficient of variation for TLL measurements were similar for the three techniques (2.69% for fast-FLAIR, 2.33% for RARE, and 2.65% for GRASE). Our results confirm that fast-FLAIR sequences detect higher lesion volumes than those detected by other magnetic resonance imaging (MRI) sequences with shorter acquisition times. However, the reproducibility of TLL measurements is comparable among fast-FLAIR, RARE, and GRASE. This suggests that when assessing MS disease burden with MRI, the choice of the pulse sequence to be used should be dictated by the clinical setting.

Adult↗

PubMed1999

Method for intracellular magnetic labeling of human mononuclear cells using approved iron contrast agents.

A method for intracellular iron labeling of human mononuclear cells (lymphocytes and monocytes) for magnetic resonance imaging (MRI) using simple incubation of cells with approved MRI iron contrast agents is presented. Labeled cells can be detected by MRI in vitro, and this suggests the possibility that the technique could become a marker for in vivo lymphocyte and monocyte trafficking studies in acute inflammatory lesions such as those in Multiple Sclerosis.

Cell Survival↗

PubMed1999

Peripheral levels of caspase-1 mRNA correlate with disease activity in patients with multiple sclerosis; a preliminary study.

The cysteine protease caspase-1 plays a crucial part in the inflammatory process due to its ability to proteolitically activate proinflammatory cytokine precursors, such as interleukin (IL)-1beta and IL-18. Multiple sclerosis is a chronic inflammatory demyelinating disease of the CNS in which the pathogenic process is mainly orchestrated by proinflammatory cytokines. The role of caspase-1 in multiple sclerosis was evaluated by measuring its mRNA levels in peripheral blood mononuclear cells (PBMCs) from seven patients with relapsing-remitting multiple sclerosis every 15 days over a 1 year period. The recorded levels were compared with clinical and MRI evidence of disease activity. Brain MRI was performed monthly in each patient. Caspase-1 mRNA levels were significantly increased in PBMCs from patients with multiple sclerosis compared with healthy controls (p<0.001). In patients with multiple sclerosis, a twofold to threefold increase of caspase-1 mRNA mean level was found in the week preceding an acute attack (p<0. 05). The magnitude of caspase-1 mRNA increase correlated with the number of new (p=0.01) but not persisting gadolinium enhancing brain MRI lesions. In conclusion, caspase-1 might be involved in the immune mediated process underlying CNS inflammation and might represent a suitable peripheral immunological marker of disease activity in multiple sclerosis.

Adult↗

PubMed1999

Reproducibility of brain MRI lesion volume measurements in multiple sclerosis using a local thresholding technique: effects of formal operator training.

The assessment of lesion load (LL) on brain magnetic resonance imaging (MRI) scans from patients with multiple sclerosis (MS) is widely used to monitor disease evolution, natural or modified by treatments. In this study, we evaluated the effect of formal operator training on the intra- and inter-observer reproducibility of LL measurements obtained by several operators in a setting similar to that of clinical trials. Proton-density (PD)-weighted, unenhanced and enhanced T1-weighted brain MRI scans were obtained from 10 MS patients. Five naive technicians assessed LL on these images, using a semiautomated local thresholding technique for lesion segmentation and marked hardcopies as a reference. Measurements were performed twice before and twice after a 20-hour operator training. Mean intra-observer measurement coefficient of variations (COV) before and after the training were 3.1 and 1.6% for PD-weighted LL, 4.3 and 1.8% for unenhanced T1-weighted LL (p < 0. 001), 4.9 and 2.0% for enhanced T1-weighted LL (p = 0.002). Mean inter-observer COV were significantly reduced after training (from 10.0 to 5.6% for PD-weighted, from 11.0 to 7.3% for unenhanced T1-weighted and from 16.0 to 6.8% for enhanced T1-weighted LL). Our data indicate that LL assessment on serial MRI scans from MS patients performed by technicians, using a local thresholding technique for lesion segmentation, is characterized by low measurement variability which may be significantly improved by a short and cost-effective training.

Brain↗

PubMed1999

Relevance of hypointense lesions on fast fluid-attenuated inversion recovery MR images as a marker of disease severity in cases of multiple sclerosis.

BACKGROUND AND PURPOSE: Hypointense lesions can be visible on fast fluid-attenuated inversion recovery (FLAIR) MR images of the brain of patients with multiple sclerosis (MS), and they may be produced by severely damaged white matter. To test the role of these lesions as an MR marker of MS severity, we assessed their relationship with clinical findings and other MR measures. METHODS: Using a 1.5-T scanner, dual-echo rapid acquisition with relaxation enhancement, fast FLAIR, and T1-weighted MR images (24 axial, 5-mm-thick contiguous interleaved sections) were obtained from 50 patients (32 with relapsing-remitting and 18 with secondary progressive MS). RESULTS: Hypointense lesions were visible on the fast FLAIR images of 19 patients (mean number of lesions, 7.8; range 1-22); their median load was 1.4 mL (range, 0.05-12.6 mL). The median lesion load was significantly higher in patients with secondary progressive MS than in those with relapsing-remitting MS on the T1-weighted images. Both the number and the load of hypointense lesions shown by fast FLAIR imaging were significantly higher in patients with secondary progressive MS. Significant correlations were found between Expanded Disability Status Scale scores and MR lesion load. A multivariate analysis showed that only the presence of hypointense lesions on fast FLAIR images significantly separated cases of relapsing-remitting MS from cases of secondary progressive MS (relative risk, 7.1; 95% confidence interval, 2.0-25.9). CONCLUSION: The presence of hypointense lesions on fast FLAIR images was a strong predictor of disease severity in cases of MS, although the low sensitivity of this approach might limit its use for the assessment of MS evolution.

Adult↗

PubMed1999

Long-term changes of magnetization transfer-derived measures from patients with relapsing-remitting and secondary progressive multiple sclerosis.

BACKGROUND AND PURPOSE: For cases of multiple sclerosis (MS), magnetization transfer (MT) imaging may provide more pathologically specific and accurate estimates of the disease process than does conventional imaging. In this study, we evaluated changes of the MT ratio (MTR) of newly enhancing lesions, the MTR of normal-appearing white matter (NAWM), the average lesion MTR, and the MT histogram-derived metrics during a 3-year follow-up period for patients with relapsing-remitting or secondary progressive MS. METHODS: Dual-echo, conventional spin-echo, and MT images were obtained from seven patients with relapsing-remitting MS, seven patients with secondary progressive MS, and five age- and sex-matched control subjects at the time of study entry and 1, 13, and 37 months later. RESULTS: Newly enhancing lesions in the patients with secondary progressive MS presented a more severe and significant MTR reduction during the follow-up period as compared with those in the relapsing-remitting group. In cases of secondary progressive MS, we also observed a significant reduction of the MTR values of the NAWM and a trend toward reduction of average lesion MTR values. The patients with MS had mean percentage changes of MT histogram-derived measures that were approximately two to 10 times higher than those of the control subjects. CONCLUSION: This preliminary 3-year follow-up study shows that newly enhancing lesions and NAWM in patients with secondary progressive MS have significantly lower MTR values than do those in patients with relapsing-remitting MS. It also shows that the tissue damage that remains after enhancement ceases is more severe in secondary progressive disease.

Adult↗

PubMed1999

A longitudinal MR study of the presymptomatic phase in a patient with clinically definite multiple sclerosis.

We describe the dynamics and the nature of the presymptomatic phase of multiple sclerosis (MS) in a patient for whom MR abnormalities suggestive of MS were found before the development of clinical symptoms. The patient was monitored with serial monthly MR imaging of the brain and spinal cord for 5 months. Disease activity during the presymptomatic phase showed imaging characteristics comparable to that of early relapsing-remitting MS in terms of enhancing lesions, duration of enhancement, and new lesions depicted by T2-weighted imaging. Measurements derived from magnetization transfer imaging suggested that the amount and degree of tissue destruction within and outside the lesions revealed by T2-weighted imaging were mild. This, together with the fact that only one of the 43 new lesions that developed during the presymptomatic phase was located in a neurologically eloquent area, may be the reason why, for a relatively long period, the patient had no clinical manifestations of MS despite the marked MR findings of disease activity.

Adult↗