Quantitative magnetic resonance imaging reflects different levels of histologically determined myelin densities in multiple sclerosis, including remyelination in inactive multiple sclerosis lesions.

Magnetic resonance imaging (MRI) of focal or diffuse myelin damage or remyelination may provide important insights into disease progression and potential treatment efficacy in multiple sclerosis (MS). We performed post-mortem MRI and histopathological myelin measurements in seven progressive MS cases to evaluate the ability of three myelin-sensitive MRI scans to distinguish different stages of MS pathology, particularly chronic demyelinated and remyelinated lesions. At 3 Tesla, we acquired two different myelin water imaging (MWI) scans and magnetisation transfer ratio (MTR) data. Histopathology included histochemical stainings for myelin phospholipids (LFB) and iron as well as immunohistochemistry for myelin proteolipid protein (PLP), CD68 (phagocytosing microglia/macrophages) and BCAS1 (remyelinating oligodendrocytes). Mixed-effects modelling determined which histopathological metric best predicted MWF and MTR in normal-appearing and diffusely abnormal white matter, active/inactive, inactive, remyelinated and ischemic lesions. Both MWI measures correlated well with each other and histology across regions, reflecting the different stages of MS pathology. MTR data showed a considerable influence of components other than myelin and a strong dependency on tissue storage duration. Both MRI and histology revealed increased myelin densities in inactive compared with active/inactive lesions. Chronic inactive lesions harboured single scattered myelin fibres indicative of low-level remyelination. Mixed-effects modelling showed that smaller differences between white matter areas were linked to PLP densities and only to a small extent confounded by iron. MWI reflects differences in myelin lipids and proteins across various levels of myelin densities encountered in MS, including low-level remyelination in chronic inactive lesions.

Risk factors for hippocampal cavities in a marginally housed population.

Cavities in the hippocampus are morphological variants of uncertain significance. Aberrant neurodevelopment along with vascular and inflammatory etiologies have been proposed. We sought to characterize these cavities and their potential risk factors in a marginally housed population, with high rates of viral infection, addiction, and mental illness. (1) The volume of hippocampal cavities (HCavs) is greater in this highly multimorbid population compared to the general population. (2) Conventional vascular risk factors such as greater age and systolic blood pressure are associated with higher HCav volume. (3) Nonprescribed substance-related risk factors such as stimulant use or dependence, and smoking are associated with increased HCav volume independent of vascular risk factors. This is a retrospective analysis of an ongoing prospective study. We analyzed baseline data, including medical history, physical exam, psychiatric diagnosis, and MRI from a total of 375 participants. Hippocampal cavities were defined as spaces isointense to CSF on T1 MRI sequences, bounded on all sides by hippocampal tissue, with a volume of at least 1 mm3 . Risk factors were evaluated using negative binomial multiple regression. Stimulant use was reported by 87.3% of participants, with stimulant dependence diagnosed in 83.3% of participants. Prevalence of cavities was 71.6%, with a mean total bilateral HCav volume of 13.89 mm3 . On average, a 1 mmHg greater systolic blood pressure was associated with a 2.17% greater total HCav volume (95% CI = [0.57%, 3.79%], p = .0076), while each cigarette smoked per day trended toward a 2.69% greater total HCav volume (95% CI = [-0.87%, 5.54%], p = .058). A diagnosis of stimulant dependence was associated with a 95.6% greater total HCav volume (95% CI = [5.39%, 263.19%], p = .0335). Hypertension and diagnosis of stimulant dependence were associated with a greater total volume of HCav.

Cerebral Small Vessel Disease, Risk Factors, and Cognition in Tenants of Precarious Housing.

BACKGROUND AND PURPOSE: We aim to describe the burden, characteristics, and cognitive associations of cerebral small vessel disease in a Canadian sample living with multimorbidity in precarious housing. METHODS: Participants received T1, T2-fluid-attenuated inversion recovery, and susceptibility-weighted imaging 3T magnetic resonance imaging sequences and comprehensive clinical, laboratory, and cognitive assessments. Cerebral small vessel disease burden was characterized using a modified Small Vessel Disease (mSVD) score. One point each was given for moderate-severe white matter hyperintensities, ≥1 cerebral microbleeds, and ≥1 lacune. Multivariable regression explored associations between mSVD score, risk factors, and cognitive performance. RESULTS: Median age of the 228 participants (77% male) was 44.7 years (range, 23.3-63.2). In n=188 participants with consistent good quality magnetic resonance imaging sequences, mSVD scores were 0 (n=127, 68%), 1 (n=50, 27%), and 2 (n=11, 6%). Overall, one-third had an mSVD ≥1 n=61 (32%); this proportion was unchanged when adding participants with missing sequences n=72/228 (32%). The most prevalent feature was white matter hyperintensities 53/218 (24%) then cerebral microbleed 16/191 (8%) and lacunes 16/228 (7%). Older age (odds ratio, 1.10 [95% CI, 1.05-1.15], P<0.001), higher diastolic blood pressure (odds ratio, 1.05 [95% CI, 1.01-1.09], P=0.008), and a history of injection drug use (odds ratio, 3.13 [95% CI, 1.07-9.16], P=0.037) had significant independent associations with a mSVD score of ≥1 in multivariable analysis. mSVD ≥1 was associated with lower performance on tests of verbal memory, sustained attention, and decision-making, contributing 4% to 5% of the variance in each cognitive domain. CONCLUSIONS: The 32% prevalence of cerebral small vessel disease in this young, socially marginalized cohort was higher than expected for age and was associated with poorer cognitive performance.

The influence of iron oxidation state on quantitative MRI parameters in post mortem human brain.

A variety of Magnetic Resonance Imaging (MRI) techniques are known to be sensitive to brain iron content. In principle, iron sensitive MRI techniques are based on local magnetic field variations caused by iron particles in tissue. The purpose of this study was to investigate the sensitivity of MR relaxation and magnetization transfer parameters to changes in iron oxidation state compared to changes in iron concentration. Therefore, quantitative MRI parameters including R1, R2, R2∗, quantitative susceptibility maps (QSM) and magnetization transfer ratio (MTR) of post mortem human brain tissue were acquired prior and after chemical iron reduction to change the iron oxidation state and chemical iron extraction to decrease the total iron concentration. All assessed parameters were shown to be sensitive to changes in iron concentration whereas only R2, R2∗ and QSM were also sensitive to changes in iron oxidation state. Mass spectrometry confirmed that iron accumulated in the extraction solution but not in the reduction solution. R2∗ and QSM are often used as markers for iron content. Changes in these parameters do not necessarily reflect variations in iron content but may also be a result of changes in the iron's oxygenation state from ferric towards more ferrous iron or vice versa.

Prevalence and Risk Factors of Brain Infarcts and Associations With Cognitive Performance in Tenants of Marginal Housing.

Background Homeless and vulnerably housed individuals are at increased risk for multimorbidity compared with the general population. We assessed prevalence of brain infarcts on neuroimaging and associations with vascular risk factors and cognitive performance in a prospective study of residents living in marginal housing. Methods and Results Two hundred twenty-eight participants underwent structured clinical interviews, targeted clinical, laboratory, and neuropsychological assessments, and magnetic resonance imaging with T1, T2-fluid-attenuated inversion recovery and susceptibility-weighted images. Subjects underwent cognitive testing to assess premorbid IQ , verbal learning and memory, inhibition, sustained attention, mental flexibility, and decision making. In this sample (mean age 44.0 years [ SD 9.4], 77% male), prevalence of conventional vascular risk factors was lower than in the general population apart from tobacco use (94%). Ten-year Framingham risk for any cardiovascular event was 11.4%±9.2%. Brain infarcts were present in 25/228 (11%). All were ischemic (40% cortical, 56% lacunar, 4% both). Participants with infarcts were older than those without (48.9±9.4 versus 43.4±9.2, P=0.006). In a multivariable regression analysis, only age remained a significant predictor of brain infarcts (odds ratio 1.08, 95% CI 1.02-1.14, P=0.004). After controlling for age and education, the presence of infarct was a significant predictor of impaired decision making on the Iowa Gambling Task of decision making (ß -28.2, 95% CI -42.7 to -14.1, P<0.001). Conclusions Prevalence of infarcts on neuroimaging in this disadvantaged, community-dwelling cohort was much higher than expected for age and was associated with impaired decision making. Further research is needed to identify individuals at highest risk who may benefit from targeted preventative strategies.

The influence of brain iron on myelin water imaging.

With myelin playing a vital role in normal brain integrity and function and thus in various neurological disorders, myelin sensitive magnetic resonance imaging (MRI) techniques are of great importance. In particular, multi-exponential T2 relaxation was shown to be highly sensitive to myelin. The myelin water imaging (MWI) technique allows to separate the T2 decay into short components, specific to myelin water, and long components reflecting the intra- and extracellular water. The myelin water fraction (MWF) is the ratio of the short components to all components. In the brain's white matter (WM), myelin and iron are closely linked via the presence of iron in the myelin generating oligodendrocytes. Iron is known to decrease T2 relaxation times and may therefore mimic myelin. In this study, we investigated if variations in WM iron content can lead to apparent MWF changes. We performed MWI in post mortem human brain tissue prior and after chemical iron extraction. Histology for iron and myelin confirmed a decrease in iron content and no change in myelin content after iron extraction. In MRI, iron extraction lead to a decrease in MWF by 26%-28% in WM. Thus, a change in MWF does not necessarily reflect a change in myelin content. This observation has important implications for the interpretation of MWI findings in previously published studies and future research.

The role of iron and myelin in orientation dependent R2* of white matter.

Brain myelin and iron content are important parameters in neurodegenerative diseases such as multiple sclerosis (MS). Both myelin and iron content influence the brain's R2* relaxation rate. However, their quantification based on R2* maps requires a realistic tissue model that can be fitted to the measured data. In structures with low myelin content, such as deep gray matter, R2* shows a linear increase with increasing iron content. In white matter, R2* is not only affected by iron and myelin but also by the orientation of the myelinated axons with respect to the external magnetic field. Here, we propose a numerical model which incorporates iron and myelin, as well as fibre orientation, to simulate R2* decay in white matter. Applying our model to fibre orientation-dependent in vivo R2* data, we are able to determine a unique solution of myelin and iron content in global white matter. We determine an averaged myelin volume fraction of 16.02 ± 2.07% in non-lesional white matter of patients with MS, 17.32 ± 2.20% in matched healthy controls, and 18.19 ± 2.98% in healthy siblings of patients with MS. Averaged iron content was 35.6 ± 8.9 mg/kg tissue in patients, 43.1 ± 8.3 mg/kg in controls, and 47.8 ± 8.2 mg/kg in siblings. All differences in iron content between groups were significant, while the difference in myelin content between MS patients and the siblings of MS patients was significant. In conclusion, we demonstrate that a model that combines myelin-induced orientation-dependent and iron-induced orientation-independent components is able to fit in vivo R2* data.

Longitudinal advanced MRI case report of white matter radiation necrosis.

Radiation necrosis mostly occurs in and near the radiation field. We used magnetic resonance imaging to study radiation-induced necrosis of atypical onset, severity, and extent following stereotactic radiosurgery for a symptomatic arteriovenous malformation. Susceptibility-sensitive imaging, T1-relaxation, myelin water imaging, and magnetic resonance spectroscopy were acquired three times up to 52 months postradiosurgery. Increasing water content outside the radiation field, contralateral neuronal loss, and gliosis were detected over time. Our findings suggest that radiation-induced vasculopathic changes spread more diffusely than previously described. An autoimmune response to brain antigens could underlie white matter changes outside the initial radiation field.

Post Mortem Validation of MRI-Identified Veins on the Surface of the Cerebral Cortex as Potential Landmarks for Neurosurgery.

Background and Objective: Image-guided neurosurgery uses information from a wide spectrum of methods to inform the neurosurgeon's judgement about which tissue to resect and which to spare. Imaging data are registered to the patient's skull so that they correspond to the intraoperative macro- and microscopic view. The correspondence between imaging and optical systems breaks down during surgery, however, as a result of cerebro-spinal fluid drain age, tissue resection, and gravity-based brain shift. In this work we investigate whether a map of surface veins, automatically segmented from MRI, could serve as additional reference system. Methods: Gradient-echo based [Formula: see text]-weighted imaging was performed on two human cadavers heads using a 7 Tesla MRI scanner. Automatic vessel segmentation was performed using the Frangi vesselness filter, and surface renderings of vessels compared with photographs of the surface of the brain following craniotomy. Results: A high level of correspondence was established between vessel maps and the post autopsy photographs. Corresponding veins, including the prominent superior anastomotic veins, could be identified in all brain lobes. Conclusion: Automatic surface vessel segmentation is feasible and the high correspondence to post autopsy photographs indicates that they could be used as an additional reference system for image-guided neurosurgery in order to maintain the correspondence between imaging and optical systems.This has the advantage over a skull-based reference system that veins are clearly visible to the surgeon and move and deform with the underlying tissue, potentially making this surface net of landmarks robust to brain shift.

Susceptibility-sensitive MRI of multiple sclerosis lesions and the impact of normal-appearing white matter changes.

Susceptibility-sensitive magnetic resonance imaging (MRI) has gained importance in multiple sclerosis (MS) research because of its versatility, high resolution and excellent sensitivity to changes in tissue structure and composition. In particular, mapping of the resonance frequency of the MR signal and quantitative susceptibility mapping (QSM) have been explored for the description of MS lesions. Many current studies utilizing these techniques attribute increases in the MR frequency or QSM to elevated tissue iron content, in addition to myelin loss. However, this common interpretation is inconsistent with recent histopathological studies. Here, we investigate the nature of MR frequency shifts related to MS lesions by comparing post-mortem MRI data with histology, and contrast them with numerical simulations of the MR signal. We demonstrate that iron accumulation is not the driving source of the MR frequency or QSM image contrast in our sample; rather, most chronic MS lesions are characterized by advanced loss of both myelin and iron. Moreover, our results suggest that the appearance of MS lesions on MR frequency maps and QSM depends on changes in the non-lesional white matter surrounding the lesions. Understanding and accounting for these changes is essential for the quantitative interpretation of MR frequency or QSM data in white matter.

Multi-echo GRE imaging of knee cartilage.

PURPOSE: To visualize healthy and abnormal articular cartilage, we investigated the potential of using the 3D multi-echo gradient echo (GRE) signal's magnitude and frequency and maps of T2* relaxation. MATERIALS AND METHODS: After optimizing imaging parameters in five healthy volunteers, 3D multi-echo GRE magnetic resonance (MR) images were acquired at 3T in four patients with chondral damage prior to their arthroscopic surgery. Average magnitude and frequency information was extracted from the GRE images, and T2* maps were generated. Cartilage abnormalities were confirmed after arthroscopy and were graded using the Outerbridge classification scheme. Regions of interest were identified on average magnitude GRE images and compared to arthroscopy. RESULTS: All four patients presented with regions of Outerbridge Grade I and II cartilage damage on arthroscopy. One patient had Grade III changes. Grade I, II, and III changes were detectable on average magnitude and T2* maps, while Grade II and higher changes were also observable on MR frequency maps. For average magnitude images of healthy volunteers, the signal-to-noise ratio of the magnitude image averaged over three echoes was 4.26 ± 0.32, 12.26 ± 1.09, 14.31 ± 1.93, and 13.36 ± 1.13 in bone, femoral, tibial, and patellar cartilage, respectively. CONCLUSION: This proof-of-principle study demonstrates the feasibility of using different imaging contrasts from the 3D multi-echo GRE scan to visualize abnormalities of the articular cartilage. © 2016 International Society for Magnetic Resonance in Medicine Level of Evidence: 1 J. MAGN. RESON. IMAGING 2017;45:1502-1513.

Investigation of the influence of carbon dioxide concentrations on cerebral physiology by susceptibility-weighted magnetic resonance imaging (SWI).

Breathing carbogen (5% CO2 / 95% O2) dramatically increases cerebral blood flow (CBF), which induces a blood oxygenation level dependent (BOLD) related vascular signal change due to the concomitantly increased oxyhemoglobin concentration in the veins. However, carbogen often causes discomfort due to its forced strong and deep breathing which also may lead to severe motion artifacts in magnetic resonance imaging. In this study, susceptibility-weighted imaging (SWI) was performed with CO2 levels of 0, 1.67%, 3.33% and 5% to measure the induced BOLD signal changes in venous vessels and brain tissue. Susceptibility-weighted imaging data from 15 healthy subjects and one patient with a brain tumor were acquired. The signal magnitude of cortical veins increased relative to pure oxygen by 3.5+/-3.8%, 10.3+/-4.5%, and 22.7+/-8.8% for CO2 concentrations of 1.67%, 3.33%, and 5%, respectively. Significant signal changes were detected in segmented white matter for 5% CO2, and gray matter for both 3.3% and 5% CO2. The influence of motion artifacts was clearly traceable by the broadening of the signal distribution in segmented tissue. Heterogeneous signal changes were observed in the patient for the same tumor regions at both 3.33% and 5% CO2. Signal phase values of white and gray matter changed only very slightly with increasing CO2. Based on our findings we recommend the reduction of CO2 concentration to about 3% when using a mixture of O2 and CO2. All subjects also reported highly improved breathing comfort at 3.3% CO2 as compared to 5%. The marginal phase change of white and gray matter supports the assumption that deoxygenated blood alone does not explain the commonly observed phase difference between the two tissues.

Investigations on the effect of caffeine on cerebral venous vessel contrast by using susceptibility-weighted imaging (SWI) at 1.5, 3 and 7 T.

Caffeine lowers the blood oxygenation level-dependent (BOLD) signal by acting as an adenosine antagonist, thus decreasing the cerebral blood flow (CBF). The aims of this study were to demonstrate the sensitivity of susceptibility-weighted imaging (SWI) to caffeine-induced changes in CBF and to investigate the time course and magnitude of signal change in caffeine-habituated and -abstinent volunteers. High-resolution susceptibility-weighted images were acquired with both groups at 1.5 T using a fully velocity compensated 3D gradient echo sequence. Following a native scan, subjects were given a tablet containing 200 mg of caffeine. Scans were repeated for about 1 h and the acquired 3D data sets were co-registered to each other. BOLD signal changes of several venous vessels were analyzed in dedicated ROIs. Maps of relative signal change clearly visualized the caffeine-induced signal response of veins. Only very weak signal changes of about -2+/-1% were found in both, grey and white matter and -1+/-2% in the ventricles. Maximum signal decrease of veins occurred 40-50 min after caffeine ingestion. The signal decrease was -16.5+/-6.5% and -22.7+/-8.3% for the caffeine users group and abstainers, respectively. The signal difference of both groups was statistically significant (Student's t-test, t=2.16, p=0.021). Data acquired at 1.5, 3 and 7 T with echo times scaled to the respective field strength display very similar temporal signal behavior.

Detection of multiple intracranial hemorrhages in a child with acute lymphocytic leukemia (ALL) by susceptibility weighted imaging (SWI).

Susceptibility weighted imaging (SWI) combines magnitude and phase information from a high-resolution, fully velocity compensated, three-dimensional (3D) gradient echo sequence. We report on the use of this MRI technique in a young patient with acute lymphocytic leukemia (ALL) and demonstrate a higher detection rate of hemorrhagic lesion in comparison with other T2*-weighted sequences.

Susceptibility weighted imaging: data acquisition, image reconstruction and clinical applications.

Susceptibility-weighted imaging (SWI) is a novel method, that combines magnitude and phase information from a high-resolution, fully velocity compensated 3D T2-weighted gradient echo sequence. Phase images are unwrapped and high pass filtered to highlight phase changes associated with venous vessels and converted into a mask that is multiplied with the corresponding phase image. This technique has been applied thus far to the imaging of tumors, vascular malformations, trauma, stroke, micro-hemorrhages, and as a functional imaging method. The purpose of this paper is to present an overview of the current status of the technique and to illustrate its potential.

Demonstration of paramagnetic and diamagnetic cerebral lesions by using susceptibility weighted phase imaging (SWI).

Susceptibility-weighted MR imaging (SWI) has become a non-invasive diagnostic modality for functional MR imaging (fMRI) of the brain and also for the imaging of tumors, injuries, malformations or microhemorrhages. SWI often enables detection of otherwise subtle abnormalities or provides additional relevant information when combined with routine MR imaging. The purpose of this article is to illustrate the potential of SWI in the discrimination of paramagnetic and diamagnetic brain lesions in neuroradiological applications.

Nonnvasive assessment of vascular architecture and function during modulated blood oxygenation using susceptibility weighted magnetic resonance imaging.

Susceptibility weighted imaging (SWI) is a BOLD-sensitive method for visualizing anatomical features such as small cerebral veins in high detail. The purpose of this study was to evaluate high-resolution SWI in combination with a modulation of blood oxygenation by breathing of air, carbogen, and oxygen and to directly visualize the effects of changing blood oxygenation on the magnetic field inside and around venous blood vessels. Signal changes associated with the response to carbogen and oxygen breathing were evaluated in different anatomic regions in healthy volunteers and in two patients with brain tumors. In the magnitude images inhalation of carbogen led to significant signal intensity changes ranging from +4.4 +/- 1.9% to +9.5 +/- 1.4% in gray matter and no significant changes in thalamus, putamen, and white matter. During oxygen breathing mean signal changes were smaller than during carbogen breathing. The method is capable of producing high-resolution functional maps of BOLD response to carbogen and oxygen breathing as well as high-resolution images of venous vasculature. Its sensitivity to changes in blood oxygenation was demonstrated by in vivo visualization of the BOLD effect via phase imaging.

Magnetic susceptibility-weighted MR phase imaging of the human brain.

BACKGROUND AND PURPOSE: MR gradient echo imaging is sensitive to the magnetic susceptibility of different tissue types. The purpose of this study was to investigate the diagnostic potential of MR phase imaging of the human brain. METHODS: High-spatial-resolution, T2*-weighted, single-echo images were acquired in five volunteers and one patient with a brain tumor on a 1.5T system by applying a 3D, first-order, velocity-compensated gradient echo sequence by using a quadrature transmit-receive head coil. Phase images were reconstructed from the raw data and unwrapped by using a region-growing phase-unwrapping algorithm. Low-spatial-frequency components originating from static background susceptibility effects were removed by high-pass filtering. RESULTS: Phase images showed excellent image contrast and revealed anatomic structures that were not visible on the corresponding magnitude images. CONCLUSION: Improved processing of susceptibility-weighted MR phase images offers a new means of contrast for neuroimaging applications.