Characterizing iron deposition in multiple sclerosis lesions using susceptibility weighted imaging

Abstract

Purpose:To investigate whether the variable forms of putative iron deposition seen with susceptibility weighted imaging (SWI) will lead to a set of multiple sclerosis (MS) lesion characteristics different than that seen in conventional MR imaging. Materials and Methods:Twenty-seven clinically definite MS patients underwent brain scans using magnetic resonance imaging including: pre-and postcontrast T1-weighted imaging, T2-weighted imaging, FLAIR, and SWI at 1.5 T, 3 T, and 4 T. MS lesions were identified separately in each imaging sequence. Lesions identified in SWI were reevaluated for their iron content using the SWI filtered phase images. Results:There were a variety of new lesion characteristics identified by SWI, and these were classified into six types. A total of 75 lesions were seen only with conventional imaging, 143 only with SWI, and 204 by both. From the iron quantification measurements, a moderate linear correlation between signal intensity and iron content (phase) was established. Conclusion:The amount of iron deposition in the brain may serve as a surrogate biomarker for different MS lesion characteristics. SWI showed many lesions missed by conventional methods and six different lesion characteristics. SWI was particularly effective at recognizing the presence of iron in MS lesions and in the basal ganglia and pulvinar thalamus. MULTIPLE SCLEROSIS (MS) is an inflammatory demyelinating and neurodegenerative disease of the central nervous system (1,2). Most patients start with a relapsing-remitting course, which has a clearly defined episode of neurologic disability and recovery. The pathologic hallmark of multiple sclerosis is the demyelinated plaque, a well-demarcated hypocellular area characterized by the loss of myelin, along with axonal loss due to (3,4), and the formation of astrocytic scars. The etiologic mechanism underlying MS is generally believed to be autoimmune inflammation (5). Nevertheless, what initiates the disease and the sequence of events underlying the development of MS is not yet well established (6).Conventional magnetic resonance imaging (MRI) has been used routinely to diagnose and monitor the disease spatially and temporally. The use of conventional MRI to measure disease activity and assess effects of therapy is now standard in clinical practice and drug trials (7). T2-weighted imaging (T2WI) is highly sensitive in the detection of hyperintensities in white matter. However, hyperintensities on T2WI can correspond to a wide spectrum of pathology, ranging from edema and mild demyelination to lesions in which the neurons and supporting glial cells are replaced by glial scars or liquid necrosis (8 -14). In addition to T2WI, Gadolinium enhancement on T1-weighted imaging (T1WI) can suggest acute inflammation, which is a marker of disease It is becoming a consensus among many studies that iron is enriched within oligodendrocytes and myelin in both normal and diseased tissue (20 -23). One explanation for such findings proposes that iron is associated with the biosynthetic enzymes ...

Assessing Abnormal Iron Content in the Deep Gray Matter of Patients with Multiple Sclerosis versus Healthy Controls

“…3,4 To a large degree but not exclusively, the imaging pathogenic landmarks of MS have been well documented mostly in WM. 5,6 To a lesser degree, investigators have noticed abnormalities in cortical regions as well, specifically near the GM/WM boundary and in GM as well. 6,7 However, whether the starting point is in the GM or WM is still unclear.…”

“…5,6 To a lesser degree, investigators have noticed abnormalities in cortical regions as well, specifically near the GM/WM boundary and in GM as well. 6,7 However, whether the starting point is in the GM or WM is still unclear. [7][8][9] Currently, there is an increased interest in studying how GM is affected 6,10,11 and particularly deep GM involvement in MS when iron deposition has been observed.…”

“…6,7 However, whether the starting point is in the GM or WM is still unclear. [7][8][9] Currently, there is an increased interest in studying how GM is affected 6,10,11 and particularly deep GM involvement in MS when iron deposition has been observed. 6,12,13 Brain iron accumulation in neurodegenerative diseases, including MS, is not new and has been shown histologically in the past.…”

“…[7][8][9] Currently, there is an increased interest in studying how GM is affected 6,10,11 and particularly deep GM involvement in MS when iron deposition has been observed. 6,12,13 Brain iron accumulation in neurodegenerative diseases, including MS, is not new and has been shown histologically in the past. 14,15 In MS, its source is likely due to myelin or oligodendrocyte debris, concentrated iron in the macrophages, or as a product of local microhemorrhages following venule wall damage.…”

Neuroimaging in Multiple Sclerosis: Neurotherapeutic Implications

“…T1/T2 relaxation is another quantitative approach that may provide a better metric for diffuse brain changes occurring beyond traditional white matter regions [108] and to quantify myelin content [109]. Quantification of brain iron levels is an area attracting intense interest [110]. Other more technically challenging approaches include molecular imaging [111] and sodium imaging [112].…”