A pilot, longitudinal, 24-week study to evaluate the effect of interferon beta-1a subcutaneous on changes in susceptibility-weighted imaging-filtered phase assessment of lesions and subcortical deep-gray matter in relapsing–remitting multiple sclerosis
Abstract:Background: Studies have shown a relationship between increased iron content and clinical progression, cognitive impairment, and brain atrophy in patients with multiple sclerosis. Altered phase, as determined by susceptibility-weighted imaging (SWI), can potentially capture iron content changes. Objective: The objective of this study was to investigate phase changes in white matter (WM) lesions and subcortical deep-gray matter (SDGM) of patients with relapsing-remitting (RR) MS treated with interferon beta-1a … Show more
“…Hypointense rings on T2*w images correlated with histologically demonstrated iron-laden microglia present at the edge of chronic active lesions [ 147 ], but both solid and shell lesions will generate rings on T2*w images [ 8 , 167 ] (shown in Figure 4 ). Susceptibility Weighted Imaging (SWI) SWI has been utilized to see differences of iron content in healthy subjects vs. MS patients [ 23 ] and to detect lesions in GM and WM [ 17 , 24 , 30 , 168 , 169 ]. Figure 4 Solid and shell susceptibility (ultrasmall superparamagnetic iron oxide particles (USPIO)) object appearance in MRI techniques.…”
Iron is considered to play a key role in the development and progression of Multiple Sclerosis (MS). In particular, iron that accumulates in myeloid cells after the blood-brain barrier (BBB) seals may contribute to chronic inflammation, oxidative stress and eventually neurodegeneration. Magnetic resonance imaging (MRI) is a well-established tool for the non-invasive study of MS. In recent years, an advanced MRI method, quantitative susceptibility mapping (QSM), has made it possible to study brain iron through in vivo imaging. Moreover, immunohistochemical investigations have helped defining the lesional and cellular distribution of iron in MS brain tissue. Imaging studies in MS patients and of brain tissue combined with histological studies have provided important insights into the role of iron in inflammation and neurodegeneration in MS.
“…Hypointense rings on T2*w images correlated with histologically demonstrated iron-laden microglia present at the edge of chronic active lesions [ 147 ], but both solid and shell lesions will generate rings on T2*w images [ 8 , 167 ] (shown in Figure 4 ). Susceptibility Weighted Imaging (SWI) SWI has been utilized to see differences of iron content in healthy subjects vs. MS patients [ 23 ] and to detect lesions in GM and WM [ 17 , 24 , 30 , 168 , 169 ]. Figure 4 Solid and shell susceptibility (ultrasmall superparamagnetic iron oxide particles (USPIO)) object appearance in MRI techniques.…”
Iron is considered to play a key role in the development and progression of Multiple Sclerosis (MS). In particular, iron that accumulates in myeloid cells after the blood-brain barrier (BBB) seals may contribute to chronic inflammation, oxidative stress and eventually neurodegeneration. Magnetic resonance imaging (MRI) is a well-established tool for the non-invasive study of MS. In recent years, an advanced MRI method, quantitative susceptibility mapping (QSM), has made it possible to study brain iron through in vivo imaging. Moreover, immunohistochemical investigations have helped defining the lesional and cellular distribution of iron in MS brain tissue. Imaging studies in MS patients and of brain tissue combined with histological studies have provided important insights into the role of iron in inflammation and neurodegeneration in MS.
“…Therefore, the presence of a powerful imaging technique for detecting of iron deposition is crucial for follow-up of MS patients. SWI technique has showed promising results for detection of iron depositions in different studies [7,9,11]. However, there are some limitations with SWI-filtered imaging for detecting iron changes in brain.…”
Section: Discussionmentioning
confidence: 99%
“…This high signal in T2W could be due to wide range of pathologies including edema, mild demyelination and glial scars. Gadolinium enhancement in T1-wighted sequence prefers acute inflammation which is a marker of disease activity [7]. New MRI techniques including magnetization transfer ratio (MTR), spectroscopy (MRS), diffusion tensor imaging (DTI) and quantitative analysis of brain volume variations have additionally been utilized in MS patients for tracing of axons and neurons diffuse alterations.…”
Section: Introductionmentioning
confidence: 99%
“…New MRI techniques including magnetization transfer ratio (MTR), spectroscopy (MRS), diffusion tensor imaging (DTI) and quantitative analysis of brain volume variations have additionally been utilized in MS patients for tracing of axons and neurons diffuse alterations. Nevertheless, these techniques have various limited specificities in relation to different pathologic elements of MS disorder [7][8][9]. This issue is called clinic-radiologic paradox [10,11].…”
Introduction: The aim of this study was to assess the potential of SWI in comparison with T2W and FLAIR sequences for evaluating the brain plaques in Multiple sclerosis. Materials and Methods: In this prospective study, the patients with confirmed diagnosis of MS were enrolled since June 2016 to January 2017. The primary collected data were age, gender, disease duration and Expanded Disability Status Scale (EDSS). All patients were undergone brain MRI consisting T2-wighted (T2W), fluid-attenuated inversion recovery (FLAIR) and susceptibility-weighted imaging (SWI) sequences. The number and volume of plaques were measured. Moreover, the detection of iron deposition and central veins in MS plaques were assessed by SWI. Results: 35 patients were enrolled and categorized into two groups based on their disease duration. 18 cases had more than 5 years' disease duration (group 1) and 17 patients had less than 5 years' disease duration (group 2). The age, gender and EDSS were not significantly different between groups. All obtained sequences showed fewer number of plaques as the disease duration was less (P<0.05). On the other hand, the calculated mean volume of plaques in obtained sequences was not different between groups. SWI has also the ability of detection iron deposition and central vein in MS plaques. Conclusion: The results of this study indicate that SWI is an additional sequence ,that together to usual MRI sequences, helps to characterize the white matter lesions detected by the conventional protocol, in multiple sclerosis diagnosis with superiority of detecting iron deposition and central veins.
“…Our iron-oxide-labeled hNSCs take advantage of this fact to enhance a blooming effect, which effectively delineates NSC volumes [53][54][55] . The phase values we report are consistent with the reduction in the cellular iron oxide content as hNSCs begin to replicate.…”
Neonatal hypoxic-ischemic brain injury (HII) can lead to devastating neurological outcomes such as cerebral palsy, epilepsy, and mental retardation. Human neural stem cell (hNSC) therapy provides new hope for the treatment of neonatal HII. These multipotent cells can aid in HII recovery by activating multiple reparative mechanisms including secretion of neurotrophic factors that enhance brain repair and plasticity. For clinical use of implanted hNSCs, methods are required to identify, quantify, track, and visualize migration and replication in an automated and reproducible fashion. In the current study, we used a model of unilateral HII in 10-day-old rat pups that were implanted with 250,000 Feridex-labeled hNSCs into the contralateral ventricle 3 days after HII. In addition to standard noninvasively acquired serial magnetic resonance imaging (MRI) sequences (11.7 and 4.7 T) that included diffusion-weighted imaging and T2-weighted imaging, we also acquired susceptibility-weighted imaging (SWI) 1-90 days after hNSC implantation. SWI is an advanced MRI method that enhances the visualization of iron-oxide-labeled hNSCs within affected regions of the injured neonatal brain. hNSC contrast was further enhanced by creating minimal intensity projections from the raw SWI magnitude images combined with phase information. Automated computational analysis using hierarchical region splitting (HRS) was applied for semiautomatic detection of hNSCs from SWI images. We found hNSCs in the ipsilateral HII lesion within the striatum and cortex adjacent to the lesion that corresponded to histological staining for iron. Quantitative phase values (radians) obtained from SWI revealed temporally evolving increased phase which reflects a decreased iron oxide content that is possibly related to cell division and the replicative capacity of the implanted hNSCs. SWI images also revealed hNSC migration from the contralateral injection site towards the ipsilateral HII lesion. Our results demonstrate that MRI-based SWI can monitor iron-labeled hNSCs in a clinically relevant manner and that automated computational methods such as HRS can rapidly identify iron-oxide-labeled hNSCs.
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