Magnetic resonance relaxation time mapping in multiple sclerosis: Normal appearing white matter and the “invisible” lesion load

doi:10.1016/0730-725X(94)92350-7

Magnetic Resonance Imaging

Volume 12, Issue 1, 1994, Pages 33-42

https://doi.org/10.1016/0730-725X(94)92350-7 Get rights and content

Abstract

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 (average 47% for T₁ or 57% for T₂ estimates) of the total (visible plus “invisible”) lesion load per slice, 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.

References (20)

J.P. Armspach et al.
In vivo determination of multiexponential T₂ relaxation times in the brain of patients with multiple sclerosis
Magn. Reson. Imaging
(1991)
L. Rumbach et al.
Nuclear magnetic resonance T₂ relaxation times in multiple sclerosis
J. Neurol. Sci.
(1991)
I.V. Allen et al.
A histological, histochemical and biochemical study of the macroscopically normal white matter in multiple sclerosis
J. Neurol. Sci.
(1979)
D. Lacomis et al.
Spin lattice relaxation (T₁) times of cerebral white matter in multiple sclerosis
Magn. Reson. Med.
(1986)
I.E.C. Ormerod et al.
The role of NMR imaging in the assessment of multiple sclerosis and isolated neurological lesions. A quantitative study
Brain
(1987)
H.B. Larsson et al.
In vivo determination of T₁ and T₂ in the brain of patients with severe but stable multiple sclerosis
Magn. Reson. Med.
(1988)
M. Brainin et al.
Changes within the “normal” cerebral white matter of multiple sclerosis patients during acute attacks and during high dose cortisone therapy assessed by means of quantitative MRI
J. Neurol. Neurosurg. Psychiatr.
(1989)
J. Kesselring et al.
Quantitative magnetic resonance imaging in multiple sclerosis: the effect of high dose methyl-prednisolone
J. Neurol. Neurosurg. Psychiatr.
(1989)
D.H. Miller et al.
Precise relaxation time measurements of normal-appearing white matter in inflammatory central nervous system disease
Magn. Reson. Med.
(1989)
D. Sappey-Marinier
High resolution NMR spectroscopy of cerebral white matter in multiple sclerosis
Magn. Reson. Med.
(1990)

There are more references available in the full text version of this article.

Cited by (120)

3D MR fingerprinting with accelerated stack-of-spirals and hybrid sliding-window and GRAPPA reconstruction
2017, NeuroImage
Citation Excerpt :
Quantitative imaging facilitates quantification of the biochemical and biophysical properties of tissues such as T1, T2 and proton density (PD), which have been demonstrated to be sensitive biomarkers for detecting diseases such as multiple sclerosis, epilepsy and cancer (Barbosa et al., 1994; Eis et al., 1995; Martin et al., 2015).
Whole-brain high-resolution quantitative imaging is extremely encoding intensive, and its rapid and robust acquisition remains a challenge. Here we present a 3D MR fingerprinting (MRF) acquisition with a hybrid sliding-window (SW) and GRAPPA reconstruction strategy to obtain high-resolution T₁, T₂ and proton density (PD) maps with whole brain coverage in a clinically feasible timeframe.
3D MRF data were acquired using a highly under-sampled stack-of-spirals trajectory with a steady-state precession (FISP) sequence. For data reconstruction, k_x-k_y under-sampling was mitigated using SW combination along the temporal axis. Non-uniform fast Fourier transform (NUFFT) was then applied to create Cartesian k-space data that are fully-sampled in the in-plane direction, and Cartesian GRAPPA was performed to resolve k_z under-sampling to create an alias-free SW dataset. T₁, T₂ and PD maps were then obtained using dictionary matching.
Phantom study demonstrated that the proposed 3D-MRF acquisition/reconstruction method is able to produce quantitative maps that are consistent with conventional quantification techniques. Retrospectively under-sampled in vivo acquisition revealed that SW + GRAPPA substantially improves quantification accuracy over the current state-of-the-art accelerated 3D MRF. Prospectively under-sampled in vivo study showed that whole brain T₁, T₂ and PD maps with 1 mm³ resolution could be obtained in 7.5 min.
3D MRF stack-of-spirals acquisition with hybrid SW + GRAPPA reconstruction may provide a feasible approach for rapid, high-resolution quantitative whole-brain imaging.
T2 relaxation time alterations underlying neurocognitive deficits in alcohol-use disorders (AUD) in an Indian population: A combined conventional ROI and voxel-based relaxometry analysis
2015, Alcohol
Long-term heavy alcohol consumption has traditionally been associated with impaired cognitive abilities, such as deficits in abstract reasoning, problem solving, verbal fluency, memory, attention, and visuospatial processing. The present study aimed at exploring these neuropsychological deficits in alcohol-use disorders (AUD) in an Indian population using the Postgraduate Institute Battery of Brain Dysfunction (PGIBBD) and their possible correlation with alterations in T2 relaxation times (T2-RT), using whole-brain voxel-based relaxometry (VBR) and conventional region of interest (ROI) approach. Multi-echo T2 mapping sequence was performed on 25 subjects with AUD and 25 healthy controls matched for age, education, and socioeconomic status. Whole-brain T2-RT measurements were conducted using VBR and conventional ROI approach. The study was carried out on a 3T whole-body MR scanner. Post processing for VBR and ROI analysis was performed using SPM 8 software and vendor-provided software, respectively. A PGIBBD test battery was conducted on all subjects to assess their cognitive abilities, and the results were reported as raw scores. VBR and ROI results revealed that AUD subjects showed prolonged T2-RTs in cerebellum bilaterally, parahippocampal gyrus bilaterally, right anterior cingulate cortex, left superior temporal gyrus, left middle frontal gyrus, and left calcarine gyrus. A significant correlation was also observed between the neuropsychological test raw scores and alterations in T2-RT in AUD subjects. Our results are consistent with previous studies suggesting tissue disruption or gliosis or demyelination as a possible reason for prolonged T2-RTs. This damage to brain tissue, which is evident as prolonged T2-RT, could possibly be associated with impaired cognitive abilities noticeable in AUD subjects.
Insights from magnetic resonance imaging
2014, Handbook of Clinical Neurology
Citation Excerpt :
The T2 RT is also an exponential time constant and represents the time required for the transverse magnitization (measured orthogonal to B0) to fall to 37% of its maximum value following the RF excitation pulse. Following the same principles of T1 RT mapping, T2 RT histograms can be constructed and may allow the discrimination of normal controls from MS patients (Barbosa et al., 1994; Grenier et al., 2002; Neema et al., 2009a), or the discrimination between RRMS, PPMS, and SPMS patients (Grenier et al., 2002). This technique, however, is more demanding than T1 RT measurement.
Recent years have witnessed impressive advancements in the use of magnetic resonance imaging (MRI) for the assessment of patients with multiple sclerosis (MS). Complementary to the clinical evaluation, conventional MRI (cMRI) provides crucial pieces of information for the diagnosis of MS, the understanding of its natural history, and monitoring the efficacy of experimental treatments. Measures derived from cMRI present clear advantages over the clinical assessment, including their more objective nature and an increased sensitivity to MS-related changes. However, the correlation between these measures and the clinical manifestations of the disease remains weak, and this can be explained, at least partially, by the limited ability of cMRI to characterize and quantify the heterogeneous features of MS pathology. Quantitative MR-based techniques have the potential to overcome the limitations of cMRI. Magnetization transfer MRI, diffusion-weighted and diffusion tensor MRI with fiber tractography, proton magnetic resonance spectroscopy, T1 and T2 relaxation time measurement, and functional MRI are contributing to elucidate the mechanisms that underlie injury, repair, and functional adaptation in patients with MS. All conventional and nonconventional MR techniques will benefit from the use of high-field MR systems (3.0 T or more).
Multiple white matter tract abnormalities underlie cognitive impairment in RRMS
2012, NeuroImage
Citation Excerpt :
Interestingly, no DTI study to date (including the present one) has found an association between memory and the uncinate fasciculus, a tract thought to be relevant in learning and memory in other diseases (Diehl et al., 2008; Nestor et al., 2004). Many studies in the last 20 years have confirmed involvement of so-called normal-appearing white matter in the pathophysiology of MS (Allen et al., 2001; Barbosa et al., 1994; Chard et al., 2002; Filippi et al., 1995; Kutzelnigg et al., 2005; Werring et al., 2000). A number of prior studies investigating the association between DTI-related measures and cognitive performance have also demonstrated the fact that there are regions of non-overlap of these associations with T2 lesions (Dineen et al., 2009; Roosendaal et al., 2009).
Diffusion tensor imaging (DTI) is a sensitive tool for detecting microstructural tissue damage in vivo. In this study, we investigated DTI abnormalities in individuals with relapsing remitting multiple sclerosis (RRMS) and examined the relations between imaging-based measures of white matter injury and cognitive impairment. DTI-derived metrics using tract-based spatial statistics (TBSS) were compared between 37 individuals with RRMS and 20 healthy controls. Cognitive impairment was assessed with three standard tests: the Symbol Digit Modalities Test (SDMT), which measures cognitive processing speed and visual working memory, the Rey Auditory Verbal Learning Test (RAVLT), which examines verbal memory, and the Paced Auditory Serial Addition Test (PASAT), which assesses sustained attention and working memory. Correlations between DTI-metrics and cognition were explored in regions demonstrating significant differences between the RRMS patients and the control group. Lower fractional anisotropy (FA) was found in RRMS participants compared to controls across the tract skeleton (0.40 ± 0.03 vs. 0.43 ± 0.01, p < 0.01). In areas of reduced FA, mean diffusivity was increased and was dominated by increased radial diffusivity with no significant change in axial diffusivity, an indication of the role of damage to CNS myelin in MS pathology. In the RRMS group, voxelwise correlations were found between FA reduction and cognitive impairment in cognitively-relevant tracts, predominantly in the posterior thalamic radiation, the sagittal stratum, and the corpus callosum; the strongest correlations were with SDMT measures, with contributions to these associations from both lesion and normal-appearing white matter. Moreover, results using threshold-free cluster enhancement (TFCE) showed more widespread white matter involvement compared to cluster-based thresholding. These findings indicate the important role for DTI in delineating mechanisms underlying MS-associated cognitive impairment and suggest that DTI could play a critical role in monitoring the clinical and cognitive effects of the disease.
In vivo quantitative evaluation of brain tissue damage in multiple sclerosis using gradient echo plural contrast imaging technique
2010, NeuroImage
Conventional MRI based on weighted spin-echo (SE) images aids in the diagnosis of multiple sclerosis (MS); however, MRI markers derived from SE sequences provide limited information about lesion severity and correlate poorly with patient disability assessed with clinical tests. In this study, we introduced a novel method [based on quantitative R2* (1/T2*) histograms] for estimating the severity of brain tissue damage in MS lesions. We applied at 1.5 T an advanced, multi-gradient echo MRI technique [gradient echo plural contrast imaging (GEPCI)] to obtain images of the brains of healthy control subjects and subjects with MS. GEPCI is a simple yet robust technique allowing simultaneous acquisition of inherently co-registered quantitative T2* and FLAIR-like maps, along with T1-weighted images within a clinically acceptable time frame. Images obtained with GEPCI appear highly similar to standard scans; hence, they can be used in a reliable and conventional way for a clinical evaluation of the disease. Yet, the main advantage of GEPCI approach is its quantitative nature. Analysis of R2* histograms of white matter revealed a difference in the distribution between healthy subjects and subjects with MS. Based on this difference, we developed a new method for grading the severity of tissue damage [tissue damage score (TDS)] in MS lesions. This method also provides a tissue damage load (TDL) assessing both lesion load and lesion severity, and a mean tissue damage score (MTDS) estimating the average MS lesion damage. We found promising correlations between the results derived from this method and the standard measure of clinical disability.
3 T MRI relaxometry detects T2 prolongation in the cerebral normal-appearing white matter in multiple sclerosis
2009, NeuroImage
MRI at 3 T has increased sensitivity in detecting overt multiple sclerosis (MS) brain lesions; a growing body of data suggests clinically relevant damage occurs in the normal-appearing white matter (NAWM). We tested a novel pulse sequence to determine whether 3 T MRI spin–spin relaxometry detected damage in NAWM of MS patients (n = 13) vs. age-matched normal controls [(NL) (n = 11)]. Baseline characteristics of the MS group were: age (mean ± SD) 42.5 ± 5.4 (range 33–51 years), disease duration 9.0 ± 6.4 (range 1–22 years), Expanded Disability Status Scale score 2.5 ± 1.7 (range 1–6.5). Brain MRI measures, obtained at 3 T, included global and regional NAWM transverse relaxation rate [R2 (= 1 / T2)], derived from 3D fast spin-echo T2 prepared images, and global white matter volume fraction derived from SPGR images. The regional NAWM areas investigated were the frontal lobe, parietal lobe, and the genu and splenium of the corpus callosum. Mean NAWM R2 was lower (indicating T2 prolongation) in MS than NL in the whole brain (p = 0.00047), frontal NAWM (p = 0.00015), parietal NAWM (p = 0.0069) and callosal genu (p = 0.0019). Similarly, R2 histogram peak position was lower in NAWM in MS than NL in the whole brain (p = 0.019). However, the normalized WM volume fractions were similar in both MS and NL (p > 0.1). This pilot study suggests that a novel 3D fast spin-echo pulse sequence at 3 T, used to derive R2 relaxation maps, can detect tissue damage in the global and regional cerebral NAWM of MS patients that is missed by conventional lesion and atrophy measures. Such findings may represent demyelination, inflammation, glial proliferation and axonal loss.

View all citing articles on Scopus

View full text

Original contributionMagnetic resonance relaxation time mapping in multiple sclerosis: Normal appearing white matter and the “invisible” lesion load

Abstract

Magn. Reson. Imaging

J. Neurol. Sci.

J. Neurol. Sci.

Spin lattice relaxation (T1) times of cerebral white matter in multiple sclerosis

Magn. Reson. Med.

The role of NMR imaging in the assessment of multiple sclerosis and isolated neurological lesions. A quantitative study

Brain

In vivo determination of T1 and T2 in the brain of patients with severe but stable multiple sclerosis

Magn. Reson. Med.

Changes within the “normal” cerebral white matter of multiple sclerosis patients during acute attacks and during high dose cortisone therapy assessed by means of quantitative MRI

J. Neurol. Neurosurg. Psychiatr.

Quantitative magnetic resonance imaging in multiple sclerosis: the effect of high dose methyl-prednisolone

J. Neurol. Neurosurg. Psychiatr.

Precise relaxation time measurements of normal-appearing white matter in inflammatory central nervous system disease

Magn. Reson. Med.

High resolution NMR spectroscopy of cerebral white matter in multiple sclerosis

Magn. Reson. Med.

Original contribution
Magnetic resonance relaxation time mapping in multiple sclerosis: Normal appearing white matter and the “invisible” lesion load

Spin lattice relaxation (T₁) times of cerebral white matter in multiple sclerosis

In vivo determination of T₁ and T₂ in the brain of patients with severe but stable multiple sclerosis