MRI Contrast Uptake In New Lesions In Relapsing/Remitting MS Followed At Weekly Intervals
Cotton F, Weiner HL, Jolesz FA, Guttmann CR
Neurology 2003 Feb 25;60(4):640-6
Harvard Medical School, Brigham & Women's Hospital, Department of Radiology, Boston, MA 02115, USA
One of the diagnostic imaging hallmarks of MS is the uptake of IV administered contrast material in new lesions in the Brain, signaling Blood-Brain Barrier breakdown and active inflammation.
Many clinical drug trials are designed based on the assumption that lesion enhancement on MRI remains visible on average for 1 month. For practical reasons, few serial MRI studies of patients with MS have been performed at intervals shorter than 4 weeks.
The authors performed a year-long longitudinal study in 26 patients with Relapsing/Remitting MS (RRMS).
Which, comprised an initial phase of MRI follow-up at weekly intervals for 8 weeks, followed by imaging every other week for another 16 weeks, and monthly thereafter.
They present a quantitative analysis (using a supervised interactive thresholding procedure) of new enhancing lesions appearing during the first 6 weeks in this cohort and evaluated from the time of first detection until enhancement was no longer seen.
The average duration of Gd-DTPA enhancement in individual new lesions was 3.07 weeks (median, 2 weeks).
Significant correlations were demonstrated between the duration of contrast enhancement or initial growth rates and lesion volumes.
Different lesions in the same patient appeared to develop largely independent of each other and demonstrated a large range in the duration of enhancement during the acute phase of their evolution.
The average duration of Blood-Brain Barrier impairment in RRMS is shorter than earlier estimates. Early lesion growth parameters may predict final lesion size.
Within-patient heterogeneity of lesion evolution suggests that individual lesions develop independently.
Fabiano AJ, Sharma J, Weinstock-Guttman B, Munschauer FE 3rd, Benedict RH, Zivadinov R, Bakshi R
J NeuroImaging 2003 Oct;13(4):307-14
Buffalo NeuroImaging Analysis Center, Jacobs Neurological Institute, 100 High Street, Buffalo, NY 14203, USA
Background And Purpose
Injury to deep Gray Matter structures in Multiple Sclerosis (MS) has been suggested by recent NeuroImaging and NeuroPathology studies.
Diffusion-weighted Magnetic Resonance Imaging (DWI) can assess tissue damage with greater sensitivity than conventional MRI.
The authors' objective was to assess Thalamic Gray Matter damage by Diffusion-weighted imaging in MS patients.
This was a retrospective study performed at a tertiary care, University-affiliated comprehensive MS center of 82 MS patients and 43 controls.
The main outcome measures were Thalamic Apparent Diffusion Coefficients (ADCs), Whole-Brain Atrophy (Brain Parenchymal Fraction), Fluid-Attenuated Inversion Recovery (FLAIR) hypertense lesion volume, and clinical course.
ADCs in the Left Thalamus were higher in MS patients (0.741 +/- 0.044 x 10(-3) mm2/s) than controls (0.723 +/- 0.036 x 10(-3) mm2/s) (P = .027).
And higher in Secondary/Progressive MS patients (0.761 +/- 0.044 x 10(-3) mm2/s), than Relapsing/Remitting MS patients (0.735 +/- 0.032 x 10(-3) mm2/s) (P = .029).
ADCs in the Right Thalamus were higher in Secondary/Progressive MS patients (0.784 +/- 0.069 x 10(-3) mm2/s) than controls (0.757 +/- 0.038 x 10(-3) mm2/s) (P = .033).
In the MS group:
- Left Thalamus ADCs correlated negatively with Brain Parenchymal Fraction (r = -0.30, P = .008)
- Total Left Hemispheric FAIR lesion volume correlated with ADCs in the:
- Left (r = 0.35, P = .001)
- Right (r = 0.39, P < .001) Thalamus
- Total Right Hemispheric FLAIR lesion volume correlated with ADCs in the:
- Left (r = 0.31, P = .006)
- Right Thalamus (r = 0.22, P = .048).
And total Right Hemispheric FLAIR lesion volume correlated with ADCs in the Left (r = 0.31, P = .006) and Right Thalami (r = 0.22, P = .048).
MS patients have increased water Diffusion in the Thalamus that is partly associated with clinical course, lesion load, and Whole-Brain Atrophy.
Both indirect and direct mechanisms of Gray Matter injury may play a role in the pathophysiology of MS.
MRI-Clinical Correlations In The Primary/Progressive Course Of MS: New Insights Into The Disease Pathophysiology From The Application Of Magnetization Transfer, Diffusion Tensor, And Functional MRI
J Neurol Sci 2003 Feb 15;206(2):157-64
Scientific Institute and University Ospedale San Raffaele, NeuroImaging Research Unit, Department of NeuroScience, Via Olgettina 60, 20132 Milan, Italy
Despite patients with Primary/Progressive Multiple Sclerosis (PPMS) experience a Progressive disease course from onset, the burden and activity of lesions on conventional Magnetic Resonance Imaging (MRI) scans of the Brain are lower than in all other main clinical phenotypes of MS.
This review outlines the major contributions given by Magnetization Transfer MRI, Diffusion Tensor MRI and Functional MRI to the understanding of the pathophysiology of PPMS.
And, provides evidence that, at least, three factors might explain this clinical/MRI discrepancy:
- Presence of diffuse tissue damage at a microscopic level
- Prevalent involvement of the Cervical Cord
- Impairment of the adaptive capacity of the Cortex
Bagnato F, Jeffries N, Richert ND, Stone RD, Ohayon JM, McFarland HF, Frank JA
Brain 2003 Aug;126(Pt 8):1782-9
National Institutes of Health, NeuroImmunology Branch, National Institute of Neurological Disorders and Stroke, Building 10, Room 5B16, 10 Center Drive MSC 1400, Bethesda, MD 20892-1400, USA
T1 Black Holes (BHs) on MRIs may represent either areas of Edema or Axonal loss in patients with Multiple Sclerosis.
BHs begin as Contrast Enhancing Lesions (CELs) and evolve differently from patient to patient, and within the same patient over time.
We analyzed BHs formation over a 4-year period. Forty-eight monthly MRIs of nine non-treated Multiple Sclerosis patients were evaluated for numbers of CELs and BHs.
A BH was defined as a HypoIntense lesion on a T1 pre-contrast image that coincided with a region of high signal intensity on the T2-weighted images.
A BH was considered as Acute (ABH) when it occurred coincidently with the presence of enhancement and as Persisting (PBH) when present after the cessation of enhancement.
The present study aimed to analyze the:
- Incidence of CELs, new PBHs, and the accumulation of PBHs
- Relationship between the quantity of CELs in a given month and,
- Likelihood of accumulating PBHs in the subsequent month
- Relationship between the duration of CELs and PBHs
Pitman's correlation test evaluated the effect of time on either the increase of CELs and new PBHs or the accumulation of PBHs.
While a multiple logistic regression analysis evaluated the relationship between progression of time and CELs, and the increase of PBHs in a multivariate model.
The relationship between the enhancing lesions duration and the PBHs duration, or the time to revert back to an IsoIntense lesion was analysed using Kaplan-Meier survival models.
PBHs accumulated (P < 0.001) in all patients, but the formation of new PBHs increased in four patients (P < or = 0.007) in conjunction with an increase in either the quantity of CELs (P < 0.001, for two patients) or the proportion of CELs turning into PBHs (P < or = 0.02, for two patients).
Logistic regression analysis showed that neither progression of time nor the number of CELs in a given month were able to predict the probability of increasing the number of PBHs in the subsequent month in any patient. Out of 397 ABHs, 55.7% evolved to a PBH.
The duration of PBHs correlated with the duration of enhancement. PBHs preceded by CELs observable on a single MRI persisted for a shorter time (P < 0.002) than those preceded by CELs visible on > or =2 monthly MRIs.
The formation of a new PBH was found to be related to CELs activity; however, duration of PBHs is most likely a consequence of the duration of the enhancement.
Traboulsee A, Dehmeshki J, Peters KR, Griffin CM, Brex PA, Silver N, Ciccarrelli O, Chard DT, Barker GJ, Thompson AJ, Miller DH
Mult Scler 2003 Dec;9(6):566-73
Institute of Neurology, University College London, NMR Research Unit, Queen Square, London WC1N 3BG, UK
Magnetization Transfer Ratio (MTR) Histogram analysis provides a global measure of disease burden in Multiple Sclerosis (MS).
MTR abnormalities in Normal-Appearing Brain Tissue (NABT) provide quantitative information on the extent of tissue damage undetected by conventional T2-weighted (T2W) Magnetic Resonance Imaging (MRI).
1) To compare the MTR Histograms from NABT across a broad spectrum of relapse onset MS patients, including Relapsing/Remitting (RR) MS (including newly diagnosed and Benign subgroups) and Secondary/Progressive (SP) MS.
2) To determine the relationship between clinical disability and NABT MTR Histograms.
2D Spin Echo Magnetization Transfer Imaging was performed on 70 RRMS and 25 SPMS patients and compared with 63 controls.
MTR Histograms were acquired for NABT after extracting lesions and CerebroSpinal Fluid (CSF). T2W images were used to measure the Brain Parenchymal Fraction (BPF) and T2 lesion load.
MS patients had a disease duration ranging from 0.5 to 37 years and an Expanded Disability Status Scale (EDSS) score ranging from 0 to 8.5.
There was a significant decrease in NABT mean MTR (+/- standard deviation) compared with controls (33.07 pu +/- 1.06 versus 34.26 pu +/- 0.47; P < 0.001) with an effect size of 2.56.
The reduction in NABT mean MTR varied among patient groups from 4.9% for SPMS, 3% for all RRMS, 2.7% for early RRMS and 2.5% for Benign MS, compared with controls.
NABT mean MTR correlated significantly with T2 lesion load (r = -0.82) and BPF (r = 0.58).
EDSS score correlated with NABT mean MTR (r = -0.43), BPF (r = -0.33) and with T2 lesion load (r = 0.59).
Multivariate analysis using NABT MTR peak height, T2 lesion load and BPF combined only accounted for 38% of the variance in the EDSS (r = 0.62; P < 0.001). Disease duration accounted for an additional 14% of variance in the EDSS (r = 0.72; P < 0.001).
There is evidence of diffuse abnormalities in NABT in addition to global Brain Atrophy in relapse onset MS patients, including those with recently diagnosed RRMS and Benign MS.
The abnormalities are greatest in patients with the more disabling SPMS. Atrophy, NABT and lesion abnormalities are all partly correlated.
The processes marked by these MR measures all contribute to disability in MS, providing complementary information relevant to the complex pathological processes that occur in MS.
Frohman EM, Goodin DS, Calabresi PA, Corboy JR, Coyle PK, Filippi M, Frank JA, Galetta SL, Grossman RI, Hawker K, Kachuck NJ, Levin MC, Phillips JT, Racke MK, Rivera VM, Stuart WH
Neurology 2003 Sep 9;61(5):602-11
Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology
University of Texas Southwestern Medical Center at Dallas, USA
Advancements in imaging technologies and newly evolving treatments offer the promise of more effective management strategies for MS.
Until recently, confirmation of the diagnosis of MS has generally required the demonstration of clinical activity that is disseminated in both time and space.
Nevertheless, with the advent of MRI techniques, occult disease activity can be demonstrated in 50 to 80% of patients at the time of the first clinical presentation.
Prospective studies have shown that the presence of such lesions predicts future conversion to Clinically Definite (CD) MS.
Indeed, in a young to middle-aged adult with a Clinically Isolated Syndrome (CIS), once alternative diagnoses are excluded at baseline.
The finding of three or more White Matter lesions on a T2-weighted MRI scan (especially if one of these lesions is located in the PeriVentricular region) is a very sensitive predictor (>80%) of the subsequent development of CDMS within the next 7 to 10 years.
Moreover, the presence of two or more Gadolinium (Gd)-enhancing lesions at baseline and the appearance of either new T2 lesions or new Gd enhancement on follow-up scans are also highly predictive of the subsequent development of CDMS in the near term.
By contrast, normal results on MRI at the time of clinical presentation makes the future development of CDMS considerably less likely.