Biomedical subjects

Simon J Francis

Publications and source records attributed to Simon J Francis.

5 recordsLinked to original sources

PubMed2005

Axonal injury in the cerebral normal-appearing white matter of patients with multiple sclerosis is related to concurrent demyelination in lesions but not to concurrent demyelination in normal-appearing white matter.

We assessed axonal injury and demyelination in the cerebral normal-appearing white matter (NAWM) of MS patients in a pilot study using proton magnetic resonance spectroscopic imaging and quantitative magnetization transfer (MT) imaging. Resonance intensities of N-acetylaspartate (NAA) relative to creatine (Cr) were measured in a large central brain volume. NAA/Cr in NAWM was estimated by regression of the NAA/Cr in each voxel against white matter fraction and extrapolation to a white matter fraction of 1. The fractional size of the semi-solid pool (F) was obtained from the binary spin bath model of MT by computing the model parameters from multiple MT-weighted and relaxometry acquisitions. F in NAWM was significantly smaller in the patients [0.109 (0.009)] relative to controls [0.123 (0.007), P = 0.011], but did not differ between RR [0.1085] and SP [0.1087] patients [P > 0.99]. NAA/Cr and F in the NAWM were not correlated (r = 0.16, P > 0.7), mainly due to a lack of variation in F among patients. This may indicate a floor to the extent of myelin pathology that can occur in NAWM before a lesion appears, or that axonal damage is not strictly related to demyelination. The correlation between NAWM NAA/Cr and T2w lesion volume was not significant (P > 0.1). However, dividing the lesion volumes by the mean F in T2w lesions resulted in a quantity that correlated well with NAWM NAA/Cr (r = -0.78, P = 0.038), possibly reflecting the association of Wallerian degeneration in the NAWM with axonal transection associated with demyelination within lesions.

Adult↗

PubMed2005

The role of edema and demyelination in chronic T1 black holes: a quantitative magnetization transfer study.

PURPOSE: To use quantitative magnetization transfer imaging (qMTI) in an investigation of T1-weighted hypointensity observed in clinical magnetic resonance imaging (MRI) scans of multiple sclerosis (MS) patients, which has previously been proposed as a more specific indicator of tissue damage than the more commonly detected T2 hyperintensity. MATERIALS AND METHODS: A cross-sectional study of 10 MS patients was performed using qMTI. A total of 60 MTI measurements were collected in each patient at a resolution of 2 x 2 x 7 mm, over a range of saturation pulses. The observed T1 and T2 were also measured. qMT model parameters were estimated using a voxel-by-voxel fit. RESULTS: A total of 65 T2-hyperintense lesions were identified; 53 were also T1 hypointense. In these black holes, the qMTI-derived semisolid pool fraction F correlated negatively with T(1,obs) (r2 = 0.76; P < 0.0001). The water pool absolute size (PDf) showed a weaker correlation with T(1,obs) (positive, r2 = 0.53; P < 0.0001). The magnetization transfer ratio (MTR) showed a similarly strong correlation with F and a weaker correlation with PDf (r2 = 0.18; P < 0.04). CONCLUSION: T1 increases in chronic black holes strongly correlated with the decline in semisolid pool size, and somewhat less to the confounding effect of edema. MTR was less sensitive than T(1,obs) to liquid pool changes associated with edema.

Adult↗

PubMed2004

The relationship between diffuse axonal damage and fatigue in multiple sclerosis.

BACKGROUND: Fatigue is a common and distressing symptom for patients with multiple sclerosis (MS). There is growing evidence that fatigue in MS has a central nervous system component. We hypothesized that diffuse cerebral axonal damage could be associated with fatigue and used proton magnetic resonance spectroscopy to noninvasively measure axonal damage or loss in the brains of patients with MS. OBJECTIVE: To assess the strength of the relationship between central brain N-acetylaspartate and fatigue. DESIGN: Data from 73 patients who had undergone proton magnetic resonance spectroscopy imaging and completed the Fatigue Severity Scale questionnaire were analyzed. RESULTS: The N-acetylaspartate-creatine ratio (NAA/Cr) was significantly lower in the high-fatigue group than the low-fatigue group (mean +/- SD, 2.69 +/- 0.29 and 2.99 +/- 0.33, respectively. P =.003). Independent of the Kurtzke Expanded Disability Status Scale, T2 lesion volume, age, and disease duration, NAA/Cr was significantly lower in the high-fatigue group as compared with the low-fatigue group. There was a statistically significant linear correlation between the Fatigue Severity Scale scores and NAA/Cr (Spearman rank rho = -0.361, P =.02). CONCLUSIONS: The results of this study, combined with those of others, suggest that widespread axonal dysfunction is associated with fatigue in MS. Increased recruitment of cortical areas and pathways in response to brain injury may be responsible for the patient's sense that the effort required to perform actions is disproportionately high.

Adult↗

PubMed2002

Diffuse axonal and tissue injury in patients with multiple sclerosis with low cerebral lesion load and no disability.

BACKGROUND: Although in situ pathological studies and in vivo magnetic resonance (MR) investigations have shown that axonal injury can be significant in the early stages of multiple sclerosis (MS), diffuse axonal injury is generally considered a secondary event. Cerebral axonal damage can be specifically assessed in vivo by measuring levels of brain N-acetylaspartate (NAA, a specific index of axonal integrity detected by MR spectroscopy). Other new MR measurements such as magnetization transfer ratio (MTr) or computed estimation of brain volume can provide less specific indexes of tissue damage. OBJECTIVE: To determine whether diffuse axonal and tissue injury is present in patients with definite MS who do not show clinically significant disability. METHODS: We measured brain NAA levels (normalized to creatine [Cr]), MTr values, and cerebral volumes in patients with definite MS who had low T2-weighted MR imaging lesion volumes and no clinical disability, and also in age-matched healthy control subjects. RESULTS: Values of central brain NAA/Cr and MTr in normal-appearing white matter were significantly lower in the MS patients than in controls (P<.001). In contrast, total brain volumes were not significantly different between these groups. Similar results were found for MS patients with early disease (duration, <3 years) and with a particularly low cerebral T2-weighted MR imaging lesion load (< or = 2 cm(3)). CONCLUSIONS: Cerebral NAA/Cr and MTr values are diffusely decreased in MS patients with early disease, low demyelinating lesion load, and no significant disability. This suggests that axonal and/or tissue injury begins very early in the course of MS and might be at least partially independent of cerebral demyelination.

Adolescent↗

PubMed2002

Magnetization transfer can predict clinical evolution in patients with multiple sclerosis.

The clinical course of multiple sclerosis (MS) is highly variable ranging from benign to aggressive, and is difficult to predict. Since magnetization transfer (MT) imaging can detect focal abnormalities in normal-appearing white matter (NAWM) before the appearance of lesions on conventional MRI, we hypothesized that changes in MT might be able to predict the clinical evolution of MS. We assessed MR data from MS patients who were subsequently followed clinically for 5 years. We computed the mean MT ratio (MTr) in gray matter, in lesions identified on T2-weighted MRI, and in NAWM, as well as in a thick central brain slice for each patient. Patients were divided into stable and worsening groups according to their change in Expanded Disability Status Scale (EDSS) scores over 5 years. We calculated the sensitivity, specificity, predictive value, and odds ratio of the baseline MTr measures in order to assess their prognostic utility. We found significant differences in baseline MTr values in NAWM (p = 0.005) and brain slice (p = 0.03) between clinically stable and worsening MS patients. When these MTr values were compared with changes in EDSS over 5 years, a strong correlation was found between the EDSS changes and MTr values in both NAWM (SRCC = -0.76, p < 0.001) and in the brain slice (SRCC = 0.59, p = 0.01). Baseline NAWM MTr correctly predicted clinical evolution in 15/18 patients (1 false positive and 2 false negatives), yielding a positive predictive value of 77.78 %, a negative predictive value of 88.89 %, and an odds ratio of 28. The relationship between 5-year changes in EDSS and MTr values in T2 weighted MRI lesions was weaker (SRCC = -0.43, p = 0.07). Our data support the notion that the quantification of MTr in the NAWM can predict the clinical evolution of MS. Lower MTr values predict poorer long-term clinical outcome. Abnormalities of MTr values in the NAWM are more relevant to the development of future patient disability than those in the T2-weighted MRI lesions.

Adult↗