Magnetization transfer histograms in clinically isolated syndromes suggestive of multiple sclerosis

Fernando, Kryshani; Tozer, Daniel J.; Miszkiel, KA; Gordon, RM; Swanton, JK; Dalton, Catherine M.; Barker, Gareth J.; Plant, Gordon T.; Thompson, Alan J.; Miller, David H.

doi:10.1093/brain/awh654

Cited by 102 publications

(79 citation statements)

References 57 publications

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“…Magnetization transfer (MT) in tissue relates to the exchange of proton magnetization between mobile water protons and protons that are immobilized by macromolecules (Wolff and Balaban, 1989). In patients with multiple sclerosis, reductions in MTR can be observed even if other imaging modalities, such as T2-and T1-weighted imaging show no abnormality making it particularly sensitive in detecting early abnormalities of normal appearing tissues including white matter (Audoin et al, 2004;Fernando et al, 2005;Iannucci et al, 2000;Traboulsee et al, 2002) and cortical (Fernando et al, 2005) as well as deep gray matter (Audoin et al, 2004). MTR reductions in normal appearing white matter might be due to astrocytic proliferation, perivascular inflammation, demyelination (Rademacher et al, 1999), and loss of axonal density (van Waesberghe et al, 1999) as well as vascular insults (Fazekas et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Basal forebrain integrity and cognitive memory profile in healthy aging

Düzel¹,

Münte²,

Lindenberger³

et al. 2010

Brain Research

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Age-related dysfunctions in cholinergic and dopaminergic neuromodulation are assumed to contribute to age-associated impairment of explicit memory. Both neurotransmitters also modulate attention, working memory, and processing speed. To date, in vivo evidence linking structural age-related changes in these neuromodulatory systems to dysfunction within or across these cognitive domains remains scarce. Using a factor analytical approach in a cross-sectional study including 86 healthy older (aged 55 to 83 years) and 24 young (aged 18 to 30 years) adults, we assessed the relationship between structural integrity-as measured by magnetization transfer ratio (MTR)-of the substantia nigra/ventral tegmental area (SN/VTA), main origin of dopaminergic projections, basal forebrain (major origin of cortical cholinergic projections), frontal white matter (FWM), and hippocampus to neuropsychological and psychosocial scores. Basal forebrain MTR and FWM changes correlated with a factor combining verbal learning and memory and working memory and, as indicated by measures of diffusion, were most likely due to vascular pathology. These findings suggest that frontal white matter integrity and cholinergic neuromodulation provide clues as to why age-related cognitive decline is often correlated across cognitive domains. IntroductionAge-related decline in learning and memory, often termed age-associated memory impairment (AAMI) (Crook et al., 1986), is a well-documented finding in healthy older adults (Balota et al., 2000;Cabeza et al., 2000;Craik, 1994;Salthouse, 2003), but the neurobiological correlates of this decline are still under debate. A consistent pattern of AAMI is a decrement in declarative memory (Tulving, 1985) most clearly apparent in impaired free recall and recollection (Buckner, 2004;Craik, 2006;Hedden and Gabrieli, 2004;Nilsson, 2003). Evidence from lesion studies in humans and animals indicates that

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Section: Discussionmentioning

confidence: 99%

Basal forebrain integrity and cognitive memory profile in healthy aging

Düzel¹,

Münte²,

Lindenberger³

et al. 2010

Brain Research

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“…Reduced GM MTR seems to be present in all MS clinical phenotypes, starting from the earliest clinical stage of the disease. [45][46][47] Such GM abnormalities, however, increase with disease duration; for example, they were found to be more pronounced in patients with PPMS or SPMS. 31 The distribution of MTR abnormalities in the different brain GM structures still needs to be defined.…”

Section: Gray Mattermentioning

confidence: 98%

“…39,40 Such pathological abnormalities modify the relative proportions of mobile and immobile protons of the diseased tissue, and so it is not surprising that MT-MRI is able to show microscopic damage in NAWM that conventional imaging fails to detect. [25][26][27] Decreased MTR values have been found, using ROI and histogram analysis, in normal-appearing brain tissue (NABT) and NAWM of MS patients, 24,29,30,[41][42][43][44][45][46][47] which can precede new lesion formation. 48 -51 NABT and NAWM MTR abnormalities have been detected in patients with CIS suggestive of MS, 29,44,46 increase progressively in early RRMS 45 and early PPMS, 47 and are more pronounced in SPMS and PPMS patients than in patients with the other main disease phenotypes.…”

Section: Mt-mri Of Normal-appearing Brain Tissue and Nawmmentioning

confidence: 99%

“…[25][26][27] Decreased MTR values have been found, using ROI and histogram analysis, in normal-appearing brain tissue (NABT) and NAWM of MS patients, 24,29,30,[41][42][43][44][45][46][47] which can precede new lesion formation. 48 -51 NABT and NAWM MTR abnormalities have been detected in patients with CIS suggestive of MS, 29,44,46 increase progressively in early RRMS 45 and early PPMS, 47 and are more pronounced in SPMS and PPMS patients than in patients with the other main disease phenotypes. 24,31,[41][42][43] Benign MS patients had NABT MTR values significantly higher than those of early RRMS patients.…”

Section: Mt-mri Of Normal-appearing Brain Tissue and Nawmmentioning

confidence: 99%

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Magnetization Transfer Magnetic Resonance Imaging of the Brain, Spinal Cord, and Optic Nerve

Filippi

Rocca

2007

Neurotherapeutics

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Summary:Magnetic resonance imaging is highly sensitive in revealing CNS abnormalities associated with several neurological conditions, but lacks specificity for their pathological substrates. In addition, MRI does not allow evaluation of the presence and extent of damage in regions that appear normal on conventional MRI sequences and that postmortem studies have shown to be affected by pathology. Quantitative MR-based techniques with increased pathological specificity to the heterogeneous substrates of CNS pathology have the potential to overcome such limitations. Among these techniques, one of the most extensively used for the assessment of CNS disorders is magnetization transfer MRI (MT-MRI). The application of this technique for the assessment of damage in macroscopic lesions, in normal-appearing white and gray matter, and in the spinal cord and optic nerve of patients with several neurological conditions is providing important in vivo information-dramatically improving our understanding of the factors associated with the appearance of clinical symptoms and the accumulation of irreversible disability. MT-MRI also has the potential to contribute to the diagnostic evaluation of several neurological conditions and to improve our ability to monitor treatment efficacy in experimental trials.

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“…Of special interest are these methods in quantifying disease burden in the normal-appearing brain tissue, particularly in CIS patients in order to get additional prognostic information [54,57,58].…”

Section: Quantitative Mri Methodsmentioning

confidence: 99%

High field MRI in the diagnosis of multiple sclerosis: high field–high yield?

Wattjes

Barkhof

2009

Neuroradiology

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Following the approval of the U.S. Food and Drug Administration (FDA), high field magnetic resonance imaging (MRI) has been increasingly incorporated into the clinical setting. Especially in the field of neuroimaging, the number of high field MRI applications has been increased dramatically. Taking advantage on increased signal-to-noise ratio (SNR) and chemical shift, higher magnetic field strengths offer new perspectives particularly in brain imaging and also challenges in terms of several technical and physical consequences. Over the past few years, many applications of high field MRI in patients with suspected and definite multiple sclerosis (MS) have been reported including conventional and quantitative MRI methods. Conventional pulse sequences at 3 T offers higher lesion detection rates when compared to 1.5 T, particularly in anatomic regions which are important for the diagnosis of patients with MS. MR spectroscopy at 3 T is characterized by an improved spectral resolution due to increased chemical shift allowing a better quantification of metabolites. It detects significant axonal damage already in patients presenting with clinically isolated syndromes and can quantify metabolites of special interest such as glutamate which is technically difficult to quantify at lower field strengths. Furthermore, the higher susceptibility and SNR offer advantages in the field of functional MRI and diffusion tensor imaging. The recently introduced new generation of ultra-high field systems beyond 3 T allows scanning in submillimeter resolution and gives new insights into in vivo MS pathology on MRI. The objectives of this article are to review the current knowledge and level of evidence concerning the application of high field MRI in MS and to give some ideas of research perspectives in the future.

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Magnetization transfer histograms in clinically isolated syndromes suggestive of multiple sclerosis

Cited by 102 publications

References 57 publications

Basal forebrain integrity and cognitive memory profile in healthy aging

Basal forebrain integrity and cognitive memory profile in healthy aging

Magnetization Transfer Magnetic Resonance Imaging of the Brain, Spinal Cord, and Optic Nerve

High field MRI in the diagnosis of multiple sclerosis: high field–high yield?

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