Imaging Cortical Lesions in Multiple Sclerosis With Ultra–High-Field Magnetic Resonance Imaging

Pitt, David; Boster, Aaron; Pei, Wei; Wohleb, Eric S.; Jasne, Adam; Zachariah, Cherian Renil; Rammohan, Kottil; Knopp, Michael V.; Schmalbrock, Petra

doi:10.1001/archneurol.2010.148

Cited by 193 publications

(244 citation statements)

References 19 publications

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“…8,31 Alternatively, optimized T2* sequences at 7T MRI demonstrate the ability to detect all neuropathologically defined CL types in vivo with similar frequency, and ex vivo validation has shown excellent retrospective sensitivity of 93% for cortical demyelination at 7T. 9,28 Among our cohort, several measures of cognitive performance were significantly associated with global WMLV and type I CL counts. The relationship between these 2 MRI metrics is quite strong and statistically significant (table 2).…”

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confidence: 69%

“…7 Although 3T DIR is an innovative improvement over conventional imaging of cortical demyelination, ultra-high-field (7T) MRI using an optimized fast low-angle shot (FLASH)-T2* sequence detects more than 5 to 7 times the number of in vivo CLs differentiated by neuropathologic type-allowing identification of subpial lesions not easily detectable on DIR imaging, and which are thought to be associated with disease progression. 8 Postmortem histopathologic-MRI correlations 9 demonstrated an excellent 93% retrospective sensitivity of ex vivo focal CL detection using 7T MRI. Our purpose was to evaluate the relationship and contribution of individual global MRI metrics focused on the cortex, including neuropathologically defined focal CL types such as subpial, leukocortical, and purely intracortical CLs at 7T, with cognitive performance and physical disability status in MS.…”

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confidence: 97%

“…Because of increased spatial resolution at 7T combined with multichannel radiofrequency technology, patient motion is exaggerated at the cortex, yielding degraded images. Although spatial resolution is excellent at ultra-high-field MRI, 8,9,28,36,37 type II CLs (the least frequent CL disclosed on histopathology inspection) remain a challenge to identify in vivo, presumably as a result of their small size relative to even this degree of resolution. In our cohort, type II CLs were exceedingly rare.…”

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confidence: 99%

“…Indeed, type II CLs smaller than 1.1 mm in diameter are less frequently detected at 7T. 9 As such, the pathophysiologic role of type II CLs is elusive. Additionally, our global cortical and WM MRI metric analysis may be most sensitive to globally distributed cognitive domains, while being insensitive to regionally driven cognitive processes.…”

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confidence: 99%

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Contribution of cortical lesion subtypes at 7T MRI to physical and cognitive performance in MS

et al. 2013

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Objectives: Evaluate cross-sectionally the contribution of focal cortical lesion (CL) subtypes at ultra-high-field MRI and traditional MRI metrics of brain damage to neurologic disability and cognitive performance in a heterogeneous multiple sclerosis (MS) cohort.Methods: Thirty-four patients with early or established disease including clinically isolated syndrome, relapsing-remitting MS, and secondary progressive MS were scanned on a human 7-tesla (7T) (Siemens) scanner to acquire fast low-angle shot (FLASH) T2*-weighted images for characterization of white matter and deep gray matter lesion volume, and CL types. Patients also underwent anatomical 3T MRI for cortical thickness estimation, and neuropsychological testing within 1 week of the 7T scan. Twenty-seven patient scans were acceptable for further analysis. Neurologic disability was measured using the Expanded Disability Status Scale.Results: Type III-IV CLs had the strongest relationship to physical disability (r 5 0.670, p , 0.0001).White matter lesion volume and type I CLs are each significantly associated with 6 of 11 neuropsychological test variables. Type III-IV CLs significantly correlate with 4 of 11 neuropsychological test variables whereas type II CLs, deep gray matter lesion volume, and cortical thickness metrics are less frequently associated with cognitive performance. Cognitive dysfunction is a common but frequently overlooked clinical manifestation of multiple sclerosis (MS). 1 Frequently affected cognitive domains include executive function, processing speed, and memory. 2 Cognitive impairment in MS deleteriously affects social and vocational activities, may result in unemployment, and appears to lead to an increased vulnerability to psychiatric illness. 3 Despite the impact of cognitive dysfunction in MS, our understanding of its pathophysiology is limited. Conclusions: Leukocortical (type I) and subpial (III-IV) CLs identified on 7T FLASH-T2Conventional and quantitative MRI have identified potential biomarkers and better defined the pathophysiology of cognitive dysfunction in MS. 4 To date, global rather than regional metrics of cortical atrophy and cortical lesion (CL) volume using double inversion recovery (DIR) sequences at 3 tesla (3T) better account for the variance seen in cognitive performance in MS-supplanting conventional white matter (WM) MRI metrics. 5,6 These findings are not entirely unexpected because MS neuropathology has highlighted the cortex as a major location of demyelination. 7 Although 3T DIR is an innovative improvement over conventional imaging

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confidence: 69%

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confidence: 97%

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confidence: 99%

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confidence: 99%

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Contribution of cortical lesion subtypes at 7T MRI to physical and cognitive performance in MS

et al. 2013

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“…In fact, a number of investigations reported a significantly reduced MTR in otherwise normal-appearing WM and GM, 92,106,[108][109][110][111][112][113][114] a close correlation between the MTR and clinical disability, 114 -117 and a potential prognostic value of magnetization transfer MR imaging. 114,118 -120 More recent studies suggest that iron-laden/activated microglia 71,121 and/or aggregates typical of small bleeding 71 cause focally increased T 2 relaxation rates and/or reduced MTR 92 within normal-appearing WM. Conflicting results 122 may be explained by heterogeneous and variable patterns in pathology, e.g., the extent of tissue damage and remyelination.…”

Section: Inflammationmentioning

confidence: 99%

<i>In Vivo</i> Brain MR Imaging at Subnanoliter Resolution: Contrast and Histology

2016

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This article provides an overview of in vivo magnetic resonance (MR) imaging contrasts obtained for mammalian brain in relation to histological knowledge. Emphasis is paid to the (1) significance of high spatial resolution for the optimization of T 1 , T 2 , and magnetization transfer contrast, (2) use of exogenous extra-and intracellular contrast agents for validating endogenous contrast sources, and (3) histological structures and biochemical compounds underlying these contrasts and (4) their relevance to neuroradiology. Comparisons between MR imaging at subnanoliter resolution and histological data indicate that (a) myelin sheaths, (b) nerve cells, and (c) the neuropil are most responsible for observed MR imaging contrasts, while (a) diamagnetic macromolecules, (b) intracellular paramagnetic ions, and (c) extracellular free water, respectively, emerge as the dominant factors. Enhanced relaxation rates due to paramagnetic ions, such as iron and manganese, have been observed for oligodendrocytes, astrocytes, microglia, and blood cells in the brain as well as for nerve cells. Taken together, a plethora of observations suggests that the delineation of specific structures in high-resolution MR imaging of mammalian brain and the absence of corresponding contrasts in MR imaging of the human brain do not necessarily indicate differences between species but may be explained by partial volume effects. Second, paramagnetic ions are required in active cells in vivo which may reduce the magnetization transfer ratio in the brain through accelerated T 1 recovery. Third, reductions of the magnetization transfer ratio may be more sensitive to a particular pathological condition, such as astrocytosis, microglial activation, inflammation, and demyelination, than changes in relaxation. This is because the simultaneous occurrence of increased paramagnetic ions (i.e., shorter relaxation times) and increased free water (i.e., longer relaxation times) may cancel T 1 or T 2 effects, whereas both processes reduce the magnetization transfer ratio.

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Multiple Sclerosis Lesions and Irreversible Brain Tissue Damage

Sinnecker¹,

Mittelstaedt²,

Dörr³

et al. 2012

Arch Neurol

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Background: In current clinical practice, T2-weighted magnetic resonance imaging (MRI) is commonly applied to quantify the accumulated multiple sclerosis (MS) lesion load, whereas T1-weighted sequences are used to differentiate edema, blood-brain barrier breakdown by contrast enhancement, and irreversible brain tissue damage (commonly called "black holes" owing to the loss of signal intensity in T1-weighted sequences). Black holes are histopathologically associated with axonal loss and severe tissue destruction. In addition, double inversion recovery techniques were developed to improve the sensitivity to cortical lesions.Objective: To demonstrate the potential of ultrahighfield 3-dimensional T1-weighted imaging using magnetization-prepared rapid acquisition and multiple gradientechoes (MPRAGE) to detect and characterize white and gray matter pathology in MS.Design: Comparative study. Setting:The patients with MS were recruited from the outpatient clinics of the NeuroCure Clinical Research Center and underwent 7-T brain MRI at the Berlin Ultrahigh Field Facility, both of which are in Berlin, Germany.Patients: Twenty patients with relapsing-remitting MS and 14 healthy controls underwent 7-T brain MRI, using a 24-channel receive head coil, and a subgroup of 18 patients with relapsing-remitting MS also underwent 1.5-T brain MRI. The imaging protocol included 2-dimensional T2-weighted fast low-angle shot (FLASH) and turbo inversion recovery magnitude (TIRM) sequences. For 3-dimensional T1-weighted imaging, the MPRAGE sequence was used. Each sequence was initially examined independently in separate analyses by an investigator blinded to all other data. In a second study, all detected lesions were retrospectively analyzed in a side-by-side comparison of all sequences.Results: By use of 7-T T2-weighted FLASH imaging, 604 cerebral lesions were detected in the patients with relapsing-remitting MS (mean, 30.2 lesions per patient [range, 2-107 lesions per patient]), but none were detected in healthy controls. Cortical pathology was visible in 10 patients (6 cortical lesions and 37 leukocortical lesions). Within the 7-T acquisitions, each lesion detected at T2-weighted sequences and/or double inversion recovery sequences was also clearly delineated on corresponding MPRAGE sequences in side-by-side analysis. However, at 1.5 T, the MPRAGE images depicted only 452 of 561 lesions visualized in T2-weighted sequences and/or double inversion recovery sequences. In contrast, when analyzing each sequence separately, we found that the 7-T MPRAGE depicted more lesions than the 7-T FLASH (728 lesions vs 584 lesions), and almost twice as many as the 1.5-T MPRAGE (399 lesions). The 7-T MPRAGE also improved the detection of cortical and leukocortical lesions (15 lesions vs 58 lesions).Conclusions: At ultrahigh-field strength, T1-weighted MPRAGE is highly sensitive in detecting MS plaques within the white and the gray brain parenchyma. Our results indicate structural damage beyond demyelination in every lesion depicted, which is in accordan...

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Imaging Cortical Lesions in Multiple Sclerosis With Ultra–High-Field Magnetic Resonance Imaging

Cited by 193 publications

References 19 publications

Contribution of cortical lesion subtypes at 7T MRI to physical and cognitive performance in MS

Contribution of cortical lesion subtypes at 7T MRI to physical and cognitive performance in MS

<i>In Vivo</i> Brain MR Imaging at Subnanoliter Resolution: Contrast and Histology

Multiple Sclerosis Lesions and Irreversible Brain Tissue Damage

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