MRI 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 Lobes 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.

Objective
To evaluate:

1. The ability of Magnetization Transfer Ratio (MTR) Histogram analysis to detect the extent of changes occurring outside MS lesions seen on conventional scans

2. Whether such changes vary in the different MS clinical phenotypes

3. Whether the changes are associated with the extent and severity of the macroscopic Lesion Load

4. The contribution to Brain Atrophy

Methods
Dual-echo, T₁-weighted, and MT scans of the Brain were obtained from 77 patients with varying MS courses and 20 age- and sex-matched control subjects.

To create MT Histograms of the Normal-Appearing Cerebral Tissue, MS Lesions were segmented from dual-echo scans, superimposed automatically, and nulled out from the coregistered and scalp-stripped MTR maps.

Average MTR, peak height, and peak position were considered. T₂ and T₁ lesion loads, average lesion MTR, and Brain Volume were also measured.

Results
Average Histogram MTR (p<0.0001) and peak position (p<0.0001) from patients with Relapsing/Remitting MS (RMMS) were lower than those from control subjects.

Patients with Primary/Progressive MS (PPMS) had lower average Histogram MTR (p = 0.002) and Histogram peak height (p = 0.01) than control subjects.

Patients with Secondary/Progressive MS (SPMS) had a lower peak height (p = 0.05) than those with RRMS. Average lesion MTR (p<0.0001) correlated highly with the Histogram MTR.

Average Histogram MTR (p<0.0001) and T₂ lesion load (p = 0.001) correlated highly with Brain Volume.

Conclusions
The amount of microscopic changes account for an important fraction of the Lesion load in MS.

They may contribute to the development of Brain Atrophy and tend to be more evident in patients with Secondary/Progressive MS.

The degree of disability and Cerebellar and BrainStem impairments in Multiple Sclerosis (MS) patients were correlated with several Magnetic Resonance Imaging (MRI) measures of Tissue Damage.

In the whole Brain, Cerebellum and BrainStem to determine the relative contributions of the factors underlying the development of Disability in MS.

Dual-echo conventional Spin-Echo, T₁-weighted and Magnetization Transfer (MT) scans were obtained from 72 patients with MS and 20 age- and sex-matched controls.

The following MRI-derived quantities were considered for the Brain as a whole, for the Cerebellum and for the BrainStem:

1. The number and volume of lesions seen on T₂-weighted images;

2. The number and volume of lesions seen on T₁-weighted images;

3. The size of these structures measured on T₁-weighted scans;

4. The average MT Ratio (MTR), peak height and peak position for the MT Histogram.

With univariate analysis, many MRI measures were significantly different in patients with different levels of Disability or Cerebellar and BrainStem Functional System Impairments.

However, with multivariate analysis, only Whole-Brain average MTR was significantly related to Physical Disability, while Cerebellar and BrainStem T₁ lesion volume and average MTR were related to Cerebellar and BrainStem Impairment.

This study shows that increased pathological damage in clinically eloquent sites is the major cause of Disability in patients with MS.

It also suggests that measures derived from MT Histogram analysis and T₁ HypoIntense lesion load should be considered when evaluating long-term MS evolution.

Objective
Magnetization Transfer Imaging (MTI) provides information about Brain damage with increased pathological specificity over conventional MRI and detects subtle abnormalities in the Normal-Appearing Brain Tissue, which go undetected with conventional scanning.

Brain MRI and MTI findings were compared in patients with Multiple Sclerosis (MS) and Systemic Immune Mediated Diseases (SIDs) affecting the CNS to investigate their roles in understanding the nature of Brain damage in these diseases.

Methods
Brain Dual Echo, T₁ weighted and MTI scans were obtained in patients affected by Systemic Lupus Erithematosus (SLE) with (NSLE, n=9) and without clinical CNS involvement (n=15), Behcet's Disease (BD) (n=5), Wegener's Granulomatosis (WG) (n=9), and AntiPhosphoLipid Antibody Syndrome (APLAS) (n=6).

Ten patients with Clinically Definite MS and 15 healthy controls also underwent the same scanning protocol.

Brain MRI and MT Ratio (MTR) images of the same subject were coregistered and postprocessed to obtain MTR Histograms of the whole Brain and of the NABT.

Results
Brain HyperIntense lesions were found in all patients with MS and with NSLE and in 5/15 patients with SLE, 5/9 with WG, 1/5 with BD, and 3/6 with APLAS.

The lesion burden in the Brain was significantly higher in patients with MS compared with all the other disease groups.

All MTR Histogram parameters were significantly different among patient subgroups.

Patients with MS had significantly lower average MTR than all except patients with NSLE and significantly lower peak height and location than patients with SLE patients with NSLE had significantly lower average MTR than patients with SLE.

Conclusions
Microscopic Brain tissue damage is relevant in patients with MS, but, apart from patients with NSLE, it seems to be absent in Systemic Immune Mediated Diseases.

Even in the presence of macroscopic MRI lesions or clinical evidence of CNS involvement.

Prolonged T₁ and/or T₂ Relaxation Times (RT) in the Normal-Appearing White Matter (NAWM) of patients with Multiple Sclerosis (MS) have been attributed either to a diffuse abnormality, or to "small lesions" undetected by visual inspection of conventional MR images.

In a comparison of Brain slices from five MS patients and five healthy control subjects, we have confirmed that the average T₁ and T₂ RTs obtained from NAWM in patients with MS are significantly prolonged (p < .04).

Quantitative pixel-by-pixel mapping shows that this overall prolongation is due to the averaging of RTs from two subfractions of NAWM.

In all patients a proportion (average 54% for T₁ and 63% for T₂) of the total White Matter pixel sample from each MR Brain slice had RT values indistinguishable from those found in the White Matter of matched healthy control subjects (i.e., "Normal Normal-Appearing White Matter," NNAWM).

Scattered throughout the NAWM were multiple small areas, often of only one or two pixels, with abnormal RT values.

These Lesions, which were revealed only by pixel-by-pixel mapping of RT, made up a significant proportion of the total lesion load per slice:
1. average Visible plus "Invisible"
   • 47% for T₁ or
   • 57% for T₂ estimates
2. and of the NAWM (average
   • 36% for T₁,
   • 27% for T₂)
   • with wide interpatient variability

Further studies of these minute lesions are required to determine their total volume in the Brain, their precise nature, evolution and relevance to the functional deficit in MS.

Previous studies suggested that Magnetization Transfer Ratio (MTR) Histograms are highly correlated with other Magnetic Resonance Imaging (MRI) measures and can be used as a reliable method for quantifying overall disease burden in Multiple Sclerosis (MS).

However, the relative influence of burden and severity of macroscopic MS lesions and degree of Brain Atrophy on various MTR Histogram parameters has not yet been fully elucidated.

Aim of the present study was to investigate which MRI measure best predicts the values of MTR Histogram parameters in MS patients. Forty-two MS patients underwent Brain Dual-Echo.

T₁-weighted and Magnetization Transfer Imaging (MTI) MRI scans. HyperIntense Lesion Load (LL) on Proton Density (PD)-weighted and HypoIntense LL on T₁-weighted images were measured using a local thresholding technique.

A measure of Brain Atrophy was derived from T₁-weighted images by computing the volume of Brain tissue segmented from a slab of five consecutive slices Rostral to the Velum Interpositum.

On MTI scans, MTR Histogram analysis was performed for the whole Brain and average lesion MTR was also calculated.

PD-weighted LL, T₁-weighted LL and Brain Volume were significantly correlated with several MTI-derived measures.

When a multivariate analysis was performed, Brain Volume alone significantly predicted the values of all the MTR Histogram-derived measures (P values ranged from 0.003 to 0.0002).

The ratio between HypoIntense T₁-weighted and HyperIntense PD-weighted LL significantly predicted average lesion MTR (P<0.05).

Our results confirm that MTR can be used as a reliable method to assess both the overall disease burden and the individual Lesion intrinsic nature in MS patients.

The significant influence of Brain Atrophy on MTR Histogram parameters supports the concept that this method also provides information on the loss of Brain Parenchyma in MS.

Serial monthly Magnetization Transfer (MT) imaging was performed to evaluate whether a change of the Normal-Appearing White Matter (NAWM), which precedes the appearance of enhancing lesions, is seen in patients with Multiple Sclerosis (MS).

Every 4 weeks for 3 months, 10 patients with Relapsing/Remitting MS were scanned with a T₁-weighted sequence, 20 minutes after injection with 0.3 mmol/kg Gadolinium-DTPA (Gd-DTPA).

During each of the monthly sessions, MT and Dual Echo scans were also performed before Gd-DTPA injection.

On coregistered images, the MT Ratio (MTR) was measured in NAWM subsequently involved by enhancing lesions, in NAWM areas on the same slices but outside any present or future MR abnormality, and in enhancing lesions at the time of their appearance.

Forty-eight new enhancing lesions with no corresponding abnormalities on previous scans were identified. Their average MTR was 33.1% (+/-8.4%).

Three, 2, and 1 month before enhancement appearance, the mean MTR in NAWM, measured from areas corresponding to future enhancing lesions, was significantly lower than the mean MTR in NAWM outside enhancing areas.

The MTR decreased steadily as the time when the enhanced lesion approached.

These results suggest that changes in the NAWM of patients with MS occur before lesions become evident on conventional MRI scans.

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.

There is now widespread agreement that serial Brain MRI is useful in monitoring treatments designed to modify the course of Multiple Sclerosis. It has been less clear whether Gadolinium enhancement is needed.

We therefore compared the relative sensitivity of long Repetition Time (TR) Spin Echo (SE) and Gadolinium enhanced short TR SE sequences in detecting active lesions.

A blind analysis of the two sequences was performed in 26 untreated patients with early Relapsing/Remitting (19) or Secondary/Progressive(seven) Multiple Sclerosis who underwent monthly MRI on four occasions (one baseline and three follow-up).

Active lesions were defined as either new or enlarged lesions on long TR SE, or new or persistent enhancing lesions on short TR SE.

In one patient there were 144 active lesions, all of which were seen with enhancement on short TR SE, but only 17 were seen on long TR SE.

Amongst the remaining 25 cases
1. A total of 106 active lesions were seen:
   • 68 (64%) were seen only with enhancement on short TR SE
   • 16 (15%) were seen only on long TR SE
   • 22 (21%) were active on both sequences

We conclude that Gadolinium enhancement markedly increases the sensitivity of monthly Brain MRI in monitoring the treatment of Relapsing/Remitting or Secondary/Progressive Multiple Sclerosis.

With this frequency of scanning, a post contrast short TR SE sequence is the most sensitive method for detecting active lesions. The smaller yet still substantial incidence of active lesions seen only on the long TR SE sequence suggests that it should also be obtained.

We studied a patient with atypical Multiple Sclerosis (MS) using high field Magnetic Resonance Image scanning and documented the evolution of the lesions from the acute phase to clinical remission.

The acute lesions showed the clear concentric structure that is characteristic of Balo's Concentric Sclerosis on Magnetic Resonance Imaging (MRI). Lesions were enhanced with Gadolinium-DTPA (Gd-DTPA).

Over a four-month period, the patient recovered clinically, with some evidence of residual intellectual impairment, and the MRI lesions regressed markedly, leaving HypoIntense areas on T₁-weighted images in the Corona Radiata.