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MRI phase changes in multiple sclerosis vs neuromyelitis optica lesions at 7T

Sinnecker, Tim; Schumacher, Sophie; Mueller, Katharina; Pache, Florence; Dusek, Petr; Harms, Lutz; Ruprecht, Klemens; Nytrova, Petra; Chawla, Sanjeev; Niendorf, Thoralf; Kister, Ilya; Paul, Friedemann; Ge, Yulin; Wuerfel, Jens
OBJECTIVE: To characterize paramagnetic MRI phase signal abnormalities in neuromyelitis optica spectrum disorder (NMOSD) vs multiple sclerosis (MS) lesions in a cross-sectional study. METHODS: Ten patients with NMOSD and 10 patients with relapsing-remitting MS underwent 7-tesla brain MRI including supratentorial T2*-weighted imaging and supratentorial susceptibility weighted imaging. Next, we analyzed intra- and perilesional paramagnetic phase changes on susceptibility weighted imaging filtered magnetic resonance phase images. RESULTS: We frequently observed paramagnetic rim-like (75 of 232 lesions, 32%) or nodular (32 of 232 lesions, 14%) phase changes in MS lesions, but only rarely in NMOSD lesions (rim-like phase changes: 2 of 112 lesions, 2%, p < 0.001; nodular phase changes: 2 of 112 lesions, 2%, p < 0.001). CONCLUSIONS: Rim-like or nodular paramagnetic MRI phase changes are characteristic for MS lesions and not frequently detectable in NMOSD. Future prospective studies should ask whether these imaging findings can be used as a biomarker to distinguish between NMOSD- and MS-related brain lesions.
PMCID:4959510
PMID: 27489865
ISSN: 2332-7812
CID: 2198592

Iron and Non-Iron-Related Characteristics of Multiple Sclerosis and Neuromyelitis Optica Lesions at 7T MRI

Chawla, S; Kister, I; Wuerfel, J; Brisset, J-C; Liu, S; Sinnecker, T; Dusek, P; Haacke, E M; Paul, F; Ge, Y
BACKGROUND AND PURPOSE: Characterization of iron deposition associated with demyelinating lesions of multiple sclerosis and neuromyelitis optica has not been well studied. Our aim was to investigate the potential of ultra-high-field MR imaging to distinguish MS from neuromyelitis optica and to characterize tissue injury associated with iron pathology within lesions. MATERIALS AND METHODS: Twenty-one patients with MS and 21 patients with neuromyelitis optica underwent 7T high-resolution 2D-gradient-echo-T2* and 3D-susceptibility-weighted imaging. An in-house-developed algorithm was used to reconstruct quantitative susceptibility mapping from SWI. Lesions were classified as "iron-laden" if they demonstrated hypointensity on gradient-echo-T2*-weighted images and/or SWI and hyperintensity on quantitative susceptibility mapping. Lesions were considered "non-iron-laden" if they were hyperintense on gradient-echo-T2* and isointense or hyperintense on quantitative susceptibility mapping. RESULTS: Of 21 patients with MS, 19 (90.5%) demonstrated at least 1 quantitative susceptibility mapping-hyperintense lesion, and 11/21 (52.4%) had iron-laden lesions. No quantitative susceptibility mapping-hyperintense or iron-laden lesions were observed in any patients with neuromyelitis optica. Iron-laden and non-iron-laden lesions could each be further characterized into 2 distinct patterns based on lesion signal and morphology on gradient-echo-T2*/SWI and quantitative susceptibility mapping. In MS, most lesions (n = 262, 75.9% of all lesions) were hyperintense on gradient-echo T2* and isointense on quantitative susceptibility mapping (pattern A), while a small minority (n = 26, 7.5% of all lesions) were hyperintense on both gradient-echo-T2* and quantitative susceptibility mapping (pattern B). Iron-laden lesions (n = 57, 16.5% of all lesions) were further classified as nodular (n = 22, 6.4%, pattern C) or ringlike (n = 35, 10.1%, pattern D). CONCLUSIONS: Ultra-high-field MR imaging may be useful in distinguishing MS from neuromyelitis optica. Different patterns related to iron and noniron pathology may provide in vivo insight into the pathophysiology of lesions in MS.
PMCID:4946971
PMID: 27012298
ISSN: 1936-959x
CID: 2052172

Neuromyelitis optica does not impact periventricular venous density versus healthy controls: a 7.0 Tesla MRI clinical study

Schumacher, Sophie; Pache, Florence; Bellmann-Strobl, Judith; Behrens, Janina; Dusek, Petr; Harms, Lutz; Ruprecht, Klemens; Nytrova, Petra; Chawla, Sanjeev; Niendorf, Thoralf; Kister, Ilya; Paul, Friedemann; Ge, Yulin; Wuerfel, Jens; Sinnecker, Tim
OBJECTIVE: To quantify the periventricular venous density in neuromyelitis optica spectrum disease (NMOSD) in comparison to that in patients with multiple sclerosis (MS) and healthy control subjects. MATERIALS AND METHODS: Sixteen patients with NMOSD, 16 patients with MS and 16 healthy control subjects underwent 7.0-Tesla (7T) MRI. The imaging protocol included T2*-weighted (T2*w) fast low angle-shot (FLASH) and fluid-attenuated inversion recovery (FLAIR) sequences. The periventricular venous area (PVA) was manually determined by a blinded investigator in order to estimate the periventricular venous density in a region of interest-based approach. RESULTS: No significant differences in periventricular venous density indicated by PVA were detectable in NMOSD versus healthy controls (p = 0.226). In contrast, PVA was significantly reduced in MS patients compared to healthy controls (p = 0.013). CONCLUSION: Unlike patients with MS, those suffering from NMOSD did not show reduced venous visibility. This finding may underscore primary and secondary pathophysiological differences between these two distinct diseases of the central nervous system.
PMID: 27072685
ISSN: 1352-8661
CID: 2078342

MR Imaging Applications in Mild Traumatic Brain Injury: An Imaging Update

Wu, Xin; Kirov, Ivan I; Gonen, Oded; Ge, Yulin; Grossman, Robert I; Lui, Yvonne W
Mild traumatic brain injury (mTBI), also commonly referred to as concussion, affects millions of Americans annually. Although computed tomography is the first-line imaging technique for all traumatic brain injury, it is incapable of providing long-term prognostic information in mTBI. In the past decade, the amount of research related to magnetic resonance (MR) imaging of mTBI has grown exponentially, partly due to development of novel analytical methods, which are applied to a variety of MR techniques. Here, evidence of subtle brain changes in mTBI as revealed by these techniques, which are not demonstrable by conventional imaging, will be reviewed. These changes can be considered in three main categories of brain structure, function, and metabolism. Macrostructural and microstructural changes have been revealed with three-dimensional MR imaging, susceptibility-weighted imaging, diffusion-weighted imaging, and higher order diffusion imaging. Functional abnormalities have been described with both task-mediated and resting-state blood oxygen level-dependent functional MR imaging. Metabolic changes suggesting neuronal injury have been demonstrated with MR spectroscopy. These findings improve understanding of the true impact of mTBI and its pathogenesis. Further investigation may eventually lead to improved diagnosis, prognosis, and management of this common and costly condition. ((c)) RSNA, 2016.
PMCID:4886705
PMID: 27183405
ISSN: 1527-1315
CID: 2111672

Whole-Brain N-Acetylaspartate Concentration Is Preserved during Mild Hypercapnia Challenge

Chawla, S; Ge, Y; Lu, H; Marshall, O; Davitz, M S; Fatterpekar, G; Soher, B J; Gonen, O
BACKGROUND AND PURPOSE: Although NAA is often used as a marker of neuronal health and integrity in neurologic disorders, its normal response to physiologic challenge is not well-established and its changes are almost always attributed exclusively to brain pathology. The purpose of this study was to test the hypothesis that the neuronal cell marker NAA, often used to assess neuronal health and integrity in neurologic disorders, is not confounded by (possibly transient) physiologic changes. Therefore, its decline, when observed by using 1H-MR spectroscopy, can almost always be attributed exclusively to brain pathology. MATERIALS AND METHODS: Twelve healthy young male adults underwent a transient hypercapnia challenge (breathing 5% CO2 air mixture), a potent vasodilator known to cause a substantial increase in CBF and venous oxygenation. We evaluated their whole-brain NAA by using nonlocalizing proton MR spectroscopy, venous oxygenation with T2-relaxation under spin-tagging MR imaging, CBF with pseudocontinuous arterial spin-labeling, and the cerebral metabolic rate of oxygen, during normocapnia (breathing room air) and hypercapnia. RESULTS: There was insignificant whole-brain NAA change (P = .88) from normocapnia to hypercapnia and back to normocapnia in this cohort, as opposed to highly significant increases: 28.0 +/- 10.3% in venous oxygenation and 49.7 +/- 16.6% in global CBF (P < 10-4); and a 6.4 +/- 10.9% decrease in the global cerebral metabolic rate of oxygen (P = .04). CONCLUSIONS: Stable whole-brain NAA during normocapnia and hypercapnia, despite significant global CBF and cerebral metabolic rate of oxygen changes, supports the hypothesis that global NAA changes are insensitive to transient physiology. Therefore, when observed, they most likely reflect underlying pathology resulting from neuronal cell integrity/viability changes, instead of a response to physiologic changes.
PMCID:4644678
PMID: 26294651
ISSN: 1936-959x
CID: 1732502

The influence of mild carbon dioxide on brain functional homotopy using resting-state fMRI

Marshall, Olga; Uh, Jinsoo; Lurie, Daniel; Lu, Hanzhang; Milham, Michael P; Ge, Yulin
Homotopy reflects the intrinsic functional architecture of the brain through synchronized spontaneous activity between corresponding bilateral regions, measured as voxel mirrored homotopic connectivity (VMHC). Hypercapnia is known to have clear impact on brain hemodynamics through vasodilation, but have unclear effect on neuronal activity. This study investigates the effect of hypercapnia on brain homotopy, achieved by breathing 5% carbon dioxide (CO2 ) gas mixture. A total of 14 healthy volunteers completed three resting state functional MRI (RS-fMRI) scans, the first and third under normocapnia and the second under hypercapnia. VMHC measures were calculated as the correlation between the BOLD signal of each voxel and its counterpart in the opposite hemisphere. Group analysis was performed between the hypercapnic and normocapnic VMHC maps. VMHC showed a diffused decrease in response to hypercapnia. Significant regional decreases in VMHC were observed in all anatomical lobes, except for the occipital lobe, in the following functional hierarchical subdivisions: the primary sensory-motor, unimodal, heteromodal, paralimbic, as well as in the following functional networks: ventral attention, somatomotor, default frontoparietal, and dorsal attention. Our observation that brain homotopy in RS-fMRI is affected by arterial CO2 levels suggests that caution should be used when comparing RS-fMRI data between healthy controls and patients with pulmonary diseases and unusual respiratory patterns such as sleep apnea or chronic obstructive pulmonary disease. Hum Brain Mapp, 2015. (c) 2015 Wiley Periodicals, Inc.
PMID: 26138728
ISSN: 1097-0193
CID: 1650092

Periventricular venous density is normal in neuromyelitis optica-preliminary data from a 7T MRI study [Meeting Abstract]

Schumacher, S; Pache, F; Behrens, J; Dusek, P; Harms, L; Ruprecht, K; Nytrova, P; Chawla, S; Niendorf, T; Kister, I; Paul, F; Ge, Y; Wurfel, J; Sinnecker, T
Background: Vascular involvement in multiple sclerosis (MS) perivascular cuffing and thickened vein walls were described decades ago. Recently, a reduced (periventricular) venous density was reported in MS, and intra-lesional venous shrinking was suggested as an in vivo marker following inflammation. Vascular abnormalities on 7T MRI images have not been investigated in neuromyelitis optica (NMO). Objective: To compare periventricular venous density in NMO, healthy controls and MS using ultra-high field (7T) MRI. Methods: 18 patients with NMO (18 female; age mean+/-SD, range: 48+/-15, 22-71 years), 18 relapsing remitting MS patients (13 female; age mean+/-SD, range: 41+/-9, 20-53 years), and 18 healthy controls (7 female; age mean+/-SD, range: 44+/-14, 20-70 years) were investigated at 7T MRI including T2*-weighted (T2*w) and fluid-attenuated inversion recovery (FLAIR) imaging to calculate the periventricular venous area (PVA in mm2) by a blinded investigator. Results: In total, we detected 131 white matter lesions in 18 NMO patients, 368 white matter lesions were visualized in MS patients, and 139 white matter lesions were depicted in HC. We did not observe any differences in periventricular venous density measured by PVA in NMO (mean+/-SD, range: 132,33+/-24,08, 97-176 mm2) versus HC (Mann-Whitney U test, p=0.171; mean+/-SD, range: 143,33+/-27,30, 88-196 mm2). Contrarily, PVA was significantly reduced in MS (Mann-Whitney U test, p=0.019; mean+/-SD, range: 118,81+/-29,63, 61-170 mm2) compared to HC as described previously. Conclusions: The periventricular venous system appeared - in contrast to
EMBASE:72058147
ISSN: 1352-4585
CID: 1840072

Age-related sperm DNA methylation changes are transmitted to offspring and associated with abnormal behavior and dysregulated gene expression

Milekic, M H; Xin, Y; O'Donnell, A; Kumar, K K; Bradley-Moore, M; Malaspina, D; Moore, H; Brunner, D; Ge, Y; Edwards, J; Paul, S; Haghighi, F G; Gingrich, J A
Advanced paternal age (APA) has been shown to be a significant risk factor in the offspring for neurodevelopmental psychiatric disorders, such as schizophrenia and autism spectrum disorders. During aging, de novo mutations accumulate in the male germline and are frequently transmitted to the offspring with deleterious effects. In addition, DNA methylation during spermatogenesis is an active process, which is susceptible to errors that can be propagated to subsequent generations. Here we test the hypothesis that the integrity of germline DNA methylation is compromised during the aging process. A genome-wide DNA methylation screen comparing sperm from young and old mice revealed a significant loss of methylation in the older mice in regions associated with transcriptional regulation. The offspring of older fathers had reduced exploratory and startle behaviors and exhibited similar brain DNA methylation abnormalities as observed in the paternal sperm. Offspring from old fathers also had transcriptional dysregulation of developmental genes implicated in autism and schizophrenia. Our findings demonstrate that DNA methylation abnormalities arising in the sperm of old fathers are a plausible mechanism to explain some of the risks that APA poses to resulting offspring.
PMID: 25092244
ISSN: 1476-5578
CID: 1729872

Intracranial relationship between arterioles and venules size-reply

Ge, Yulin; Marshall, Olga; Lu, Hanzhang
PMID: 25581863
ISSN: 2168-6149
CID: 1459792

Magnetic Resonance Phase Alterations in Multiple Sclerosis Patients with Short and Long Disease Duration

Bozin, Ivan; Ge, Yulin; Kuchling, Joseph; Dusek, Petr; Chawla, Sanjeev; Harms, Lutz; Ruprecht, Klemens; Niendorf, Thoralf; Paul, Friedemann; Kister, Ilya; Sinnecker, Tim; Wuerfel, Jens
OBJECTIVE: The analysis of the MR phase provides additional information on the tissue microstructure. In multiple sclerosis (MS) lesions phase alterations may reflect different stages of inflammatory activity. Here we investigated lesion morphology in MS patients with short and long disease duration on T2* weighted, phase, magnitude and susceptibility weighted imaging (SWI) at 7 Tesla (T). METHODS: 17 MS or clinically isolated syndrome patients with short (<60 months) and 11 with long (>60 months) disease duration underwent 7T MRI. Lesions were subsequently analyzed side-by-side with regard to morphology and visibility on T2* weighted, SWI, magnitude and SWI-filtered phase images. RESULTS: 126 of 192 T2* weighted lesions (65.6%) were characterized by a phase alteration pattern, and hence could be differentiated on phase images. In detail, a significantly reduced proportion of lesions showing phase alterations was detectable in patients with longer disease duration (mean+/-SD 51+/-37%, range 0-100%) compared to patients with short disease duration (mean+/-SD 90+/-19.5%, range 50-100%, p = 0.003). CONCLUSION: This cross-sectional study identified different patterns of phase changes in lesions of MS patients with short and long standing disease. Longitudinal studies are warranted to prove that MR phase imaging is useful in determining the activity and the developmental stage of individual MS plaques.
PMCID:4506094
PMID: 26186349
ISSN: 1932-6203
CID: 1669092