Quantitative Susceptibility Mapping: Technical Considerations and Clinical Applications in Neuroimaging.

Quantitative susceptibility mapping (QSM) is a novel magnetic resonance imaging (MRI) technique for quantifying the spatial distribution of magnetic susceptibility within an object or tissue. Recently, QSM has been widely used to study various dominant magnetic susceptibility sources in the brain, including iron and calcium. In addition, the method enables mapping of the cerebral metabolic rate of oxygen, which could act as a new metabolic biomarker for diseases that involve disruption of the brain's oxygen supply. Thus, the clinical applications of QSM are wide-reaching and hold great promise as imaging biomarkers for studying several neurological diseases. This review aims to summarize the physical concepts and potential clinical applications of QSM in neuroimaging. EVIDENCE LEVEL: 5 TECHNICAL EFFICACY: Stage 2.

Regional Cerebral Blood Flow in the Posterior Cingulate and Precuneus and the Entorhinal Cortical Atrophy Score Differentiate Mild Cognitive Impairment and Dementia Due to Alzheimer Disease.

BACKGROUND AND PURPOSE: Alzheimer disease is the most common degenerative dementia affecting humans and mild cognitive impairment is considered the forerunner of this devastating illness with variable progression. Differentiating between them has become all the more essential with the advent of disease-modifying medications. The aim of this study was to test the utility of the entorhinal cortical atrophy score in combination with quantitative CBF in the posterior cingulate and precuneus using arterial spin-labeling to differentiate mild cognitive impairment and early Alzheimer disease. MATERIALS AND METHODS: We analyzed MR imaging from a prospective data base of 3 age-matched groups: 21 cognitively healthy controls, 20 patients with mild cognitive impairment, and 19 patients with early Alzheimer disease. The highest entorhinal cortical atrophy score and an atlas-based measurement of CBF in the posterior cingulate and precuneus were estimated in these groups. Statistical comparison was performed among the groups for disease-prediction probability with these parameters independently and in combination using a binary logistic regression model. RESULTS: The entorhinal cortical atrophy score performed well in distinguishing AD from HC, with a predicted probability of .887 (area under the curve, P < .001). The mean CBF of the posterior cingulate and precuneus was also found to be a useful discriminator (area under the curve, 0.810, P = < .001). Combining the entorhinal cortical atrophy score and CBF was the best predictor (area under the curve, 0.957, P < .001). In distinguishing mild cognitive impairment and Alzheimer disease, entorhinal cortical atrophy also did well with an area under the curve of 0.838 (P < .001). However regional CBF was not useful in differentiating them (area under the curve = 0.589, P = .339). Entorhinal cortical atrophy scored poorly in distinguishing mild cognitive impairment from healthy controls (AUC = 0.571, P = .493), but CBF fared well, with an area under the curve of 0.776 (P = .002). CONCLUSIONS: Combining entorhinal cortical atrophy and regional CBF could be a potential imaging biomarker in distinguishing mild cognitive impairment and Alzheimer disease.

Construction of Indian human brain atlas.

CONTEXT: A brain magnetic resonanace imaging (MRI) atlas plays an important role in many neuroimage analysis tasks as it provides an atlas with a standard coordinate system which is needed for spatial normalization of a brain MRI. Ideally, this atlas should be as near to the average brain of the population being studied as possible. AIMS: The aim of this study is to construct and validate the Indian brain MRI atlas of young Indian population and the corresponding structure probability maps. SETTINGS AND DESIGN: This was a population-specific atlas generation and validation process. MATERIALS AND METHODS: 100 young healthy adults (M/F = 50/50), aged 21-30 years, were recruited for the study. Three different 1.5-T scanners were used for image acquisition. The atlas and structure maps were created using nonrigid groupwise registration and label-transfer techniques. COMPARISON AND VALIDATION: The generated atlas was compared against other atlases to study the population-specific trends. RESULTS: The atlas-based comparison indicated a signifi cant difference between the global size of Indian and Caucasian brains. This difference was noteworthy for all three global measures, namely, length, width, and height. Such a comparison with the Chinese and Korean brain templates indicate all 3 to be comparable in length but signifi cantly different (smaller) in terms of height and width. CONCLUSIONS: The findings confirm that there is significant difference in brain morphology between Indian, Chinese, and Caucasian populations.

Multimodality Neuroimaging in Mild Cognitive Impairment: A Cross-sectional Comparison Study.

BACKGROUND AND PURPOSE: Mild cognitive impairment (MCI) is a focus of considerable research. The present study aimed to test the utility of a logistic regression-derived classifier, combining specific quantitative multimodal magnetic resonance imaging (MRI) data for the early objective phenotyping of MCI in the clinic, over structural MRI data. METHODS: Thirty-three participants with cognitively stable amnestic MCI; 15 MCI converters to early Alzheimer's disease (AD; diseased controls) and 20 healthy controls underwent high-resolution T1-weighted volumetric MRI, diffusion tensor imaging (DTI), and proton magnetic resonance spectroscopy (1H MR spectroscopy). The regional volumes were obtained from T1-weighted MRI. The fractional anisotropy and mean diffusivity maps were derived from DTI over multiple white matter regions. The 1H MRS voxels were placed over posterior cingulate gyri, and N-acetyl aspartate (NAA)/creatine (Cr), choline (Cho)/Cr, myoinositol (mI/Cr), and NAA/mI ratios were obtained. A multimodal classifier comprising MR volumetry, DTI, and MRS was prepared. A cutoff point was arrived based on receiver operator characteristics analysis. Results were considered significant, if P < 0.05. RESULTS: The most sensitive individual marker to discriminate MCI from controls was DTI (90.9%), with a specificity of 50%. For classifying MCI from AD, the best individual modality was DTI (72.7%), with a high specificity of 87.9%. The multimodal classifier approach for MCI control classification achieved an area under curve (AUC) (AUC = 0.89; P < 0.001), with 93.9% sensitivity and 70% specificity. The combined classifier for MCI-AD achieved a highest AUC (AUC = 0.93; P < 0.001), with 93% sensitivity and 85.6% specificity. CONCLUSIONS: The combined method of gray matter atrophy, white matter tract changes, and metabolite variation achieved a better performance at classifying MCI compared to the application of individual MRI biomarkers.

Reduced brain volumes in children of women with epilepsy: A neuropsychological and voxel based morphometric analysis in pre-adolescent children.

BACKGROUND AND PURPOSE: Children of Women with Epilepsy with antenatal exposure to antiepileptic drugs (CAED) have reduced neuropsychological functions. We aimed to explore the anatomical basis for this impairment by comparing the brain volumes of CAED with that of matched healthy children without antenatal AED exposure (COAED). MATERIALS AND METHODS: CAED aged 8-12 years were recruited from the Kerala Registry of epilepsy and pregnancy that prospectively follows up children of women with epilepsy and COAED from children attending the imaging department for minor illnesses. Maternal clinical details and the neuropsychological data including IQ of CAED and COAED were obtained. Total intracranial volume (TBV), grey matter volume (GMV), white matter volume (WMV) and volumes of deep grey matter were measured by Voxel Based Morphometry. RESULTS: We studied 30 CAED (mean age 10.8+1.11 years) and 35 COAED (mean age 10.64+1.26). The antenatal AED exposure for the CAED was monotherapy for 8 children and polytherapy for 22 children. The CAED had significantly lower (P<0.001) IQ (77.5+13.8), TBV(1259.55±169.85mL) and GMV (672.51±85.42 mL) compared to the IQ (87.0+13.5), TBV(1405.37±161mL) and GMV (745.427±86.69 mL) of COAED. CAED had lower volumes for Lt Inferior Triangular Gyrus, and hippocampi on both sides, when compared to COAED. Group analysis CAED showed less GMV (P<0.05) for left inferior and middle frontal gyri relative to COAED. CONCLUSIONS: These observations point towards an anatomical basis of lower GMV for the lower neuropsychological functions in children with antenatal AED exposure.

Structural correlates of mild cognitive impairment: A clinicovolumetric study.

CONTEXT:: Annually 10-12% of patients with mild cognitive impairment (MCI) are likely to progress to Alzheimer's Disease (AD). The morphometric profile in stable non-converters has not been adequately characterized. AIMS: To determine the structural differences between amnestic MCI and early AD using volumetric magnetic resonance imaging (MRI) and its correlation with neuropsychological test performances. SETTINGS AND DESIGN:: This was a hospital-based case-control study. MATERIALS AND METHODS:: Twenty-four patients classified as having "non-progressor" MCI, 13 as having an early AD, and 25 controls, and assessed using neuropsychological evaluation, and three-dimensional T1-weighted 1.5T magnetic resonance maging (MRI) were included in the study. We used both voxel-based morphometry and automated regional volumetry to assess the topographical patterns of volume loss. STATISTICAL ANALYSIS USED: Post-hoc analysis of variance was done for comparison between means, and partial correlation analysis was done for correlating volumetric and cognitive measures. RESULTS:: Consistently, significant atrophy of the superior temporal gyrus, left hippocampus, and mesial frontoparietal regions were identified in patients with MCI in comparison to controls. Increased atrophy in the limbic regions, temporal neocortex, and precuneus was identified in patients with early AD in comparison to patients with MCI. While differences in retention and recall scores between the groups were independent of age and volumetric variables, significant correlations were observed between the learning and recall scores and the volume of hippocampus in patients with MCI as well as temporal neocortex in patients with AD. Atrophy of the superior temporal gyrus and mesial neocortical regions represents the structural correlate of amnestic MCI parallel to the development of hippocampal atrophy. CONCLUSIONS:: Identification of the pattern of volumetric abnormalities in patients with amnestic MCI in addition to atrophy of the medial temporal lobes necessitates a close follow up to continuously assess these patients for their progression to early AD.

Assessment of Iron Deposition in the Brain in Frontotemporal Dementia and Its Correlation with Behavioral Traits.

BACKGROUND AND PURPOSE: Brain iron deposition has been implicated as a major culprit in the pathophysiology of neurodegeneration. However, the quantitative assessment of iron in behavioral variant frontotemporal dementia and primary progressive aphasia brains has not been performed, to our knowledge. The aim of our study was to investigate the characteristic iron levels in the frontotemporal dementia subtypes using susceptibility-weighted imaging and report its association with behavioral profiles. MATERIALS AND METHODS: This prospective study included 46 patients with frontotemporal dementia (34 with behavioral variant frontotemporal dementia and 12 with primary progressive aphasia) and 34 age-matched healthy controls. We performed behavioral and neuropsychological assessment in all the subjects. The quantitative iron load was determined on SWI in the superior frontal gyrus and temporal pole, precentral gyrus, basal ganglia, anterior cingulate, frontal white matter, head and body of the hippocampus, red nucleus, substantia nigra, insula, and dentate nucleus. A linear regression analysis was performed to correlate iron content and behavioral scores in patients. RESULTS: The iron content of the bilateral superior frontal and temporal gyri, anterior cingulate, putamen, right hemispheric precentral gyrus, insula, hippocampus, and red nucleus was higher in patients with behavioral variant frontotemporal dementia than in controls. Patients with primary progressive aphasia had increased iron levels in the left superior temporal gyrus. In addition, right superior frontal gyrus iron deposition discriminated behavioral variant frontotemporal dementia from primary progressive aphasia. A strong positive association was found between apathy and iron content in the superior frontal gyrus and disinhibition and iron content in the putamen. CONCLUSIONS: Quantitative assessment of iron deposition with SWI may serve as a new biomarker in the diagnostic work-up of frontotemporal dementia and help distinguish frontotemporal dementia subtypes.

A Potential Biomarker in Amyotrophic Lateral Sclerosis: Can Assessment of Brain Iron Deposition with SWI and Corticospinal Tract Degeneration with DTI Help?

BACKGROUND AND PURPOSE: Iron-mediated oxidative stress plays a pivotal role in the pathogenesis of amyotrophic lateral sclerosis. This study aimed to assess iron deposition qualitatively and quantitatively by using SWI and microstructural changes in the corticospinal tract by using DTI in patients with amyotrophic lateral sclerosis. MATERIALS AND METHODS: Seventeen patients with amyotrophic lateral sclerosis and 15 age- and sex-matched controls underwent brain MR imaging with SWI and DTI. SWI was analyzed for both signal-intensity scoring and quantitative estimation of iron deposition in the anterior and posterior banks of the motor and sensory cortices and deep gray nuclei. The diffusion measurements along the corticospinal tract at the level of pons and medulla were obtained by ROI analysis. RESULTS: Patients with amyotrophic lateral sclerosis showed reduced signal-intensity grades in the posterior bank of the motor cortex bilaterally. Quantitative analysis confirmed significantly higher iron content in the posterior bank of the motor cortex in patients with amyotrophic lateral sclerosis. In contrast, no significant differences were noted for the anterior bank of the motor cortex, anterior and posterior banks of the sensory cortex, and deep nuclei. Receiver operating characteristic comparison showed a cutoff of 35µg Fe/g of tissue with an area under the curve of 0.78 (P = .008) for the posterior bank of the motor cortex in discriminating patients with amyotrophic lateral sclerosis from controls. Fractional anisotropy was lower in the pyramidal tracts of patients with amyotrophic lateral sclerosis at the pons and medulla on either side, along with higher directionally averaged mean diffusivity values. The combination of SWI and DTI revealed an area under the curve of 0.784 for differentiating patients with amyotrophic lateral sclerosis from controls. CONCLUSIONS: Measurements of motor cortex iron deposition and diffusion tensor parameters of the corticospinal tract may be useful biomarkers for the diagnosis of clinically suspected amyotrophic lateral sclerosis.

A review of neuroimaging biomarkers of Alzheimer's disease.

Neuroimaging biomarkers have potential role in the early diagnosis as well as periodic follow-up of neurodegenerative diseases such as Alzheimer's disease (AD). Structural imaging biomarkers can be used to predict those who are at risk or in preclinical stages of AD. It could possibly be useful even in predicting the conversion of Mild Cognitive Impairment (MCI) an early stage of AD to AD. In addition there has been a lot of progress in molecular imaging in AD. This article presents a review of recent progress in selected imaging biomarkers for early diagnosis, classification, and progression, of AD. A comprehensive integrative strategy initiated early in the cognitive decline is perhaps the most effective method of controlling progression to Alzheimer's disease.