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 ...
Conventional clinical neuroimaging is insensitive to axonal injury in traumatic brain injury (TBI). Immunocytochemical staining reveals changes to axonal morphology within hours, suggesting potential for diffusion-weighted magnetic resonance (MR) in early diagnosis and management of TBI. Diffusion tensor imaging (DTI) characterizes the three-dimensional (3D) distribution of water diffusion, which is highly anisotropic in white matter fibers owing to axonal length. Recently, DTI has been used to investigate traumatic axonal injury (TAI), emphasizing regional analysis in more severe TBI. In the current study, we hypothesized that a global white matter (WM) analysis of DTI data would be sensitive to TAI across a spectrum of TBI severity and injury to scan interval. To investigate this, we compared WM-only histograms of a scalar, fractional anisotropy (FA), between 20 heterogeneous TBI patients recruited from Detroit Medical Center, including six mild TBI (GCS 13-15), and 14 healthy age-matched controls. FA histogram parameters were correlated with admission GCS and posttraumatic amnesia (PTA). In all cases, including mild TBI, patients' FA histograms were globally decreased compared with control histograms. The shape of the TBI histograms also differed from controls, being more peaked and skewed. The mean FA, kurtosis and skewness were highly correlated suggesting a common mechanism. FA histogram properties also correlated with injury severity indexed by GCS and PTA, with mean FA being the best predictor and duration of PTA (r = 0.64) being superior to GCS (r = 0.47). Therefore, in this heterogeneous sample, the FA mean accounted for 40% of the variance in PTA. Increased diffusion in the short axis dimension, likely reflecting dysmyelination and swelling of axons, accounted for most of the FA decrease. FA is globally deceased in WM, including mild TBI, possibly reflecting widespread involvement. FA changes appear to be correlated with injury severity suggesting a role in early diagnosis and prognosis of TBI.
Glatiramer acetate (GA) is a disease-modifying therapy for relapsing-remitting multiple sclerosis (RRMS) with several putative mechanisms of action. Currently, there is paucity of in vivo human data linking the well-established peripheral immunologic effects of therapy with GA to its potential effects inside the central nervous system (CNS). Brain proton magnetic resonance spectroscopy (MRS) allows in vivo examination of axonal integrity by quantifying the resonance intensity of the neuronal marker N-acetylaspartate (NAA). In a pilot study to investigate the effect of GA on axonal injury, we performed combined brain magnetic resonance imaging (MRI) and MRS studies in 18 treatment naïve RRMS patients initiating therapy with GA at baseline and annually for two years on therapy. A small group of four treatment naïve RRMS patients, electing to remain untreated, served as controls. NAA/Cr was measured in a large central brain volume of interest (VOI) as well as the normal appearing white matter (NAWM) within the VOI. After two years, NAA/Cr in the GA-treated group increased significantly by 10.7% in the VOI (2.17 +/- 0.26 versus 1.96 +/- 0.24, P = 0.03) and by 71% in the NAWM (2.23 +/- 0.26 versus 2.08 +/- 0.31, P = 0.04). In the untreated group, NAA/Cr decreased by 8.9% at two years in the VOI (2.01 +/- 0.16 versus 1.83 +/- 0.21, P = 0.03) and 8.2% in the NAWM (2.07 +/- 0.24 versus 1.90 +/- 0.29, P = 0.03). Our data shows that treatment with GA leads to axonal metabolic recovery and protection from sub-lethal axonal injury. These results support an in situ effect of GA therapy inside the CNS and suggest potential neuroprotective effects of GA.
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