Imaging Neurochemistry and Brain Structure Tracks Clinical Decline and Mechanisms of ALS in Patients.

Background: Oxidative stress and protein aggregation are key mechanisms in amyotrophic lateral sclerosis (ALS) disease. Reduced glutathione (GSH) is the most important intracellular antioxidant that protects neurons from reactive oxygen species. We hypothesized that levels of GSH measured by MR spectroscopic imaging (MRSI) in the motor cortex and corticospinal tract are linked to clinical trajectory of ALS patients. Objectives: Investigate the value of GSH imaging to probe clinical decline of ALS patients in combination with other neurochemical and structural parameters. Methods: Twenty-four ALS patients were imaged at 3 T with an advanced MR protocol. Mapping GSH levels in the brain is challenging, and for this purpose, we used an optimized spectral-edited 3D MRSI sequence with real-time motion and field correction to image glutathione and other brain metabolites. In addition, our imaging protocol included (i) an adiabatic T1ρ sequence to image macromolecular fraction of brain parenchyma, (ii) diffusion tensor imaging (DTI) for white matter tractography, and (iii) high-resolution anatomical imaging. Results: We found GSH in motor cortex (r = -0.431, p = 0.04) and corticospinal tract (r = -0.497, p = 0.016) inversely correlated with time between diagnosis and imaging. N-Acetyl-aspartate (NAA) in motor cortex inversely correlated (r = -0.416, p = 0.049), while mean water diffusivity (r = 0.437, p = 0.033) and T1ρ (r = 0.482, p = 0.019) positively correlated with disease progression measured by imputed change in revised ALS Functional Rating Scale. There is more decrease in the motor cortex than in the white matter for GSH compared to NAA, glutamate, and glutamine. Conclusions: Our study suggests that a panel of biochemical and structural imaging biomarkers defines a brain endophenotype, which can be used to time biological events and clinical progression in ALS patients. Such a quantitative brain endophenotype may stratify ALS patients into more homogeneous groups for therapeutic interventions compared to clinical criteria.

A protein corona sensor array detects breast and prostate cancers.

Following exposure to human plasma (HP), nanoparticles (NPs) are coated with a biomolecular layer referred to as a protein corona. We recently revealed that characterizing the protein coronas of various NPs may provide a unique opportunity for cancer identification and discrimination. In other words, protein corona profiles of several NPs, when being analyzed using classifiers, would provide a unique "fingerprint" for each type of disease. Here, we probed the capacity of the protein corona for the identification and discrimination of breast and prostate cancer patients from healthy individuals. Using three lipid NP formulations with distinct physical-chemical properties as a cross-reactive sensor array and a supervised random forest classifier, we identified a set of proteins that showed a significant difference in cancer patients and control subjects. Our data show that many of the corona proteins with the highest discrimination ability between oncological patients and healthy individuals are related to cellular and molecular aspects of breast and prostate cancers.

Super-Resolution Whole-Brain 3D MR Spectroscopic Imaging for Mapping D-2-Hydroxyglutarate and Tumor Metabolism in Isocitrate Dehydrogenase 1-mutated Human Gliomas.

Background Isocitrate dehydrogenase (IDH) mutations are highly frequent in glioma, producing high levels of the oncometabolite D-2-hydroxyglutarate (D-2HG). Hence, D-2HG represents a valuable imaging marker for IDH-mutated human glioma. Purpose To develop and evaluate a super-resolution three-dimensional (3D) MR spectroscopic imaging strategy to map D-2HG and tumor metabolism in IDH-mutated human glioma. Materials and Methods Between March and September 2018, participants with IDH1-mutated gliomas and healthy participants were prospectively scanned with a 3-T whole-brain 3D MR spectroscopic imaging protocol optimized for D-2HG. The acquired D-2HG maps with a voxel size of 5.2 × 5.2 × 12 mm were upsampled to a voxel size of 1.7 × 1.7 × 3 mm using a super-resolution method that combined weighted total variation, feature-based nonlocal means, and high-spatial-resolution anatomic imaging priors. Validation with simulated healthy and patient data and phantom measurements was also performed. The Mann-Whitney U test was used to check that the proposed super-resolution technique yields the highest peak signal-to-noise ratio and structural similarity index. Results Three participants with IDH1-mutated gliomas (mean age, 50 years ± 21 [standard deviation]; two men) and three healthy participants (mean age, 32 years ± 3; two men) were scanned. Twenty healthy participants (mean age, 33 years ± 5; 16 men) underwent a simulation of upsampled MR spectroscopic imaging. Super-resolution upsampling improved peak signal-to-noise ratio and structural similarity index by 62% (P < .05) and 7.3% (P < .05), respectively, for simulated data when compared with spline interpolation. Correspondingly, the proposed method significantly improved tissue contrast and structural information for the acquired 3D MR spectroscopic imaging data. Conclusion High-spatial-resolution whole-brain D-2-hydroxyglutarate imaging is possible in isocitrate dehydrogenase 1-mutated human glioma by using a super-resolution framework to upsample three-dimensional MR spectroscopic images acquired at lower resolution. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Huang and Lin in this issue.

The Impact of Arterial Input Function Determination Variations on Prostate Dynamic Contrast-Enhanced Magnetic Resonance Imaging Pharmacokinetic Modeling: A Multicenter Data Analysis Challenge, Part II.

This multicenter study evaluated the effect of variations in arterial input function (AIF) determination on pharmacokinetic (PK) analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data using the shutter-speed model (SSM). Data acquired from eleven prostate cancer patients were shared among nine centers. Each center used a site-specific method to measure the individual AIF from each data set and submitted the results to the managing center. These AIFs, their reference tissue-adjusted variants, and a literature population-averaged AIF, were used by the managing center to perform SSM PK analysis to estimate Ktrans (volume transfer rate constant), ve (extravascular, extracellular volume fraction), kep (efflux rate constant), and τi (mean intracellular water lifetime). All other variables, including the definition of the tumor region of interest and precontrast T1 values, were kept the same to evaluate parameter variations caused by variations in only the AIF. Considerable PK parameter variations were observed with within-subject coefficient of variation (wCV) values of 0.58, 0.27, 0.42, and 0.24 for Ktrans, ve, kep, and τi, respectively, using the unadjusted AIFs. Use of the reference tissue-adjusted AIFs reduced variations in Ktrans and ve (wCV = 0.50 and 0.10, respectively), but had smaller effects on kep and τi (wCV = 0.39 and 0.22, respectively). kep is less sensitive to AIF variation than Ktrans, suggesting it may be a more robust imaging biomarker of prostate microvasculature. With low sensitivity to AIF uncertainty, the SSM-unique τi parameter may have advantages over the conventional PK parameters in a longitudinal study.

Effect of Region of Interest Size on the Repeatability of Quantitative Brain Imaging Biomarkers.

In the repeatability analysis, when the measurement is the mean value of a parametric map within a region of interest (ROI), the ROI size becomes important as by increasing the size, the measurement will have a smaller variance. This is important in decision-making in prospective clinical studies of brain when the ROI size is variable, e.g., in monitoring the effect of treatment on lesions by quantitative MRI, and in particular when the ROI is small, e.g., in the case of brain lesions in multiple sclerosis. Thus, methods to estimate repeatability measures for arbitrary sizes of ROI are desired. We propose a statistical model of the values of parametric map within the ROI and a method to approximate the model parameters, based on which we estimate a number of repeatability measures including repeatability coefficient, coefficient of variation, and intraclass correlation coefficient for an ROI with an arbitrary size. We also show how this gives an insight into related problems such as spatial smoothing in voxel-wise analysis. Experiments are conducted on simulated data as well as on scan-rescan brain MRI of healthy subjects. The main application of this study is the adjustment of the decision threshold based on the lesion size in treatment monitoring.

Contribution of Quantitative Amygdalar MR FLAIR Signal Analysis for Lateralization of Mesial Temporal Lobe Epilepsy.

BACKGROUND AND PURPOSE: This study evaluates the contribution of an automated amygdalar fluid-attenuated inversion recovery (FLAIR) signal analysis for the lateralization of mesial temporal lobe epilepsy (mTLE). METHODS: Sixty-nine patients (27 M, 42 F) who had undergone surgery and achieved an Engel class Ia postoperative outcome were identified as a pure cohort of mTLE cases. Forty-six nonepileptic subjects comprised the control group. The amygdala was segmented in T1-weighted images using an atlas-based segmentation. The right/left ratios of amygdalar FLAIR mean and standard deviation were calculated for each subject. A linear classifier (ie, discriminator line) was designed for lateralization using the FLAIR features and a boundary domain, within which lateralization was assumed to be less definitive, was established using the same features from control subjects. Hippocampal FLAIR and volume analysis was performed for comparison. RESULTS: With the boundary domain in place, lateralization accuracy was found to be 70% with hippocampal FLAIR and 67% with hippocampal volume. Taking amygdalar analysis into account, 22% of cases that were found to have uncertain lateralization by hippocampal FLAIR analysis were confidently lateralized by amygdalar FLAIR. No misclassified case was found outside the amygdalar FLAIR boundary domain. CONCLUSIONS: Amygdalar FLAIR analysis provides an additional metric by which to establish mTLE in those cases where hippocampal FLAIR and volume analysis have failed to provide lateralizing information.

Volumetric relationship between 2-hydroxyglutarate and FLAIR hyperintensity has potential implications for radiotherapy planning of mutant IDH glioma patients.

BACKGROUND: Gliomas with mutant isocitrate dehydrogenase (IDH) produce high levels of 2-hydroxyglutarate (2HG) that can be quantitatively measured by 3D magnetic resonance spectroscopic imaging (MRSI). Current glioma MRI primarily relies upon fluid-attenuated inversion recovery (FLAIR) hyperintensity for treatment planning, although this lacks specificity for tumor cells. Here, we investigated the relationship between 2HG and FLAIR in mutant IDH glioma patients to determine whether 2HG mapping is valuable for radiotherapy planning. METHODS: Seventeen patients with mutant IDH1 gliomas were imaged by 3 T MRI. A 3D MRSI sequence was employed to specifically image 2HG. FLAIR imaging was performed using standard clinical protocol. Regions of interest (ROIs) were determined for FLAIR and optimally thresholded 2HG hyperintensities. The overlap, displacement, and volumes of 2HG and FLAIR ROIs were calculated. RESULTS: In 8 of 17 (47%) patients, the 2HG volume was larger than FLAIR volume. Across the entire cohort, the mean volume of 2HG was 35.3 cc (range, 5.3-92.7 cc), while the mean volume of FLAIR was 35.8 cc (range, 6.3-140.8 cc). FLAIR and 2HG ROIs had mean overlap of 0.28 (Dice coefficients range, 0.03-0.57) and mean displacement of 12.2 mm (range, 3.2-23.5 mm) between their centers of mass. CONCLUSIONS: Our results indicate that for a substantial number of patients, the 2HG volumetric assessment of tumor burden is more extensive than FLAIR volume. In addition, there is only partial overlap and asymmetric displacement between the centers of FLAIR and 2HG ROIs. These results may have important implications for radiotherapy planning of IDH mutant glioma.

The Impact of Arterial Input Function Determination Variations on Prostate Dynamic Contrast-Enhanced Magnetic Resonance Imaging Pharmacokinetic Modeling: A Multicenter Data Analysis Challenge.

Dynamic contrast-enhanced MRI (DCE-MRI) has been widely used in tumor detection and therapy response evaluation. Pharmacokinetic analysis of DCE-MRI time-course data allows estimation of quantitative imaging biomarkers such as Ktrans(rate constant for plasma/interstitium contrast reagent (CR) transfer) and ve (extravascular and extracellular volume fraction). However, the use of quantitative DCE-MRI in clinical prostate imaging islimited, with uncertainty in arterial input function (AIF, i.e., the time rate of change of the concentration of CR in the blood plasma) determination being one of the primary reasons. In this multicenter data analysis challenge to assess the effects of variations in AIF quantification on estimation of DCE-MRI parameters, prostate DCE-MRI data acquired at one center from 11 prostate cancer patients were shared among nine centers. Each center used its site-specific method to determine the individual AIF from each data set and submitted the results to the managing center. Along with a literature population averaged AIF, these AIFs and their reference-tissue-adjusted variants were used by the managing center to perform pharmacokinetic analysis of the DCE-MRI data sets using the Tofts model (TM). All other variables including tumor region of interest (ROI) definition and pre-contrast T1 were kept the same to evaluate parameter variations caused by AIF variations only. Considerable pharmacokinetic parameter variations were observed with the within-subject coefficient of variation (wCV) of Ktrans obtained with unadjusted AIFs as high as 0.74. AIF-caused variations were larger in Ktrans than ve and both were reduced when reference-tissue-adjusted AIFs were used. The parameter variations were largely systematic, resulting in nearly unchanged parametric map patterns. The CR intravasation rate constant, kep (= Ktrans/ve), was less sensitive to AIF variation than Ktrans (wCV for unadjusted AIFs: 0.45 for kepvs. 0.74 for Ktrans), suggesting that it might be a more robust imaging biomarker of prostate microvasculature than Ktrans.

Comparative performance evaluation of automated segmentation methods of hippocampus from magnetic resonance images of temporal lobe epilepsy patients.

PURPOSE: Segmentation of the hippocampus from magnetic resonance (MR) images is a key task in the evaluation of mesial temporal lobe epilepsy (mTLE) patients. Several automated algorithms have been proposed although manual segmentation remains the benchmark. Choosing a reliable algorithm is problematic since structural definition pertaining to multiple edges, missing and fuzzy boundaries, and shape changes varies among mTLE subjects. Lack of statistical references and guidance for quantifying the reliability and reproducibility of automated techniques has further detracted from automated approaches. The purpose of this study was to develop a systematic and statistical approach using a large dataset for the evaluation of automated methods and establish a method that would achieve results better approximating those attained by manual tracing in the epileptogenic hippocampus. METHODS: A template database of 195 (81 males, 114 females; age range 32-67 yr, mean 49.16 yr) MR images of mTLE patients was used in this study. Hippocampal segmentation was accomplished manually and by two well-known tools (FreeSurfer and hammer) and two previously published methods developed at their institution [Automatic brain structure segmentation (ABSS) and LocalInfo]. To establish which method was better performing for mTLE cases, several voxel-based, distance-based, and volume-based performance metrics were considered. Statistical validations of the results using automated techniques were compared with the results of benchmark manual segmentation. Extracted metrics were analyzed to find the method that provided a more similar result relative to the benchmark. RESULTS: Among the four automated methods, ABSS generated the most accurate results. For this method, the Dice coefficient was 5.13%, 14.10%, and 16.67% higher, Hausdorff was 22.65%, 86.73%, and 69.58% lower, precision was 4.94%, -4.94%, and 12.35% higher, and the root mean square (RMS) was 19.05%, 61.90%, and 65.08% lower than LocalInfo, FreeSurfer, and hammer, respectively. The Bland-Altman similarity analysis revealed a low bias for the ABSS and LocalInfo techniques compared to the others. CONCLUSIONS: The ABSS method for automated hippocampal segmentation outperformed other methods, best approximating what could be achieved by manual tracing. This study also shows that four categories of input data can cause automated segmentation methods to fail. They include incomplete studies, artifact, low signal-to-noise ratio, and inhomogeneity. Different scanner platforms and pulse sequences were considered as means by which to improve reliability of the automated methods. Other modifications were specially devised to enhance a particular method assessed in this study.

Standard chemoradiation for glioblastoma results in progressive brain volume loss.

OBJECTIVE: To investigate the effects of chemotherapy and cranial irradiation on normal brain tissue using in vivo neuroimaging in patients with glioblastoma. METHODS: We used longitudinal MRI to monitor structural brain changes during standard treatment in patients newly diagnosed with glioblastoma. We assessed volumetric and diffusion tensor imaging measures in 14 patients receiving 6 weeks of chemoradiation, followed by up to 6 months of temozolomide chemotherapy alone. We examined changes in whole brain, gray matter (GM), white matter (WM), anterior lateral ventricle, and hippocampal volumes. Normal-appearing GM, WM, and hippocampal analyses were conducted within the hemisphere of lowest/absent tumor burden. We examined diffusion tensor imaging measures within the subventricular zone. RESULTS: Whole brain (F = 2.41; p = 0.016) and GM (F = 2.13; p = 0.036) volume decreased during treatment, without significant WM volume change. Anterior lateral ventricle volume increased significantly (F = 65.51; p < 0.001). In participants analyzed beyond 23 weeks, mean ventricular volume increased by 42.2% (SE: 8.8%; t = 4.94; p < 0.005). Apparent diffusion coefficient increased within the subventricular zone (F = 7.028; p < 0.001). No significant changes were identified in hippocampal volume. CONCLUSIONS: We present evidence of significant and progressive treatment-associated structural brain changes in patients with glioblastoma treated with standard chemoradiation. Future studies using longitudinal neuropsychological evaluation are needed to characterize the functional consequences of these structural changes.

Repeatability of Cerebral Perfusion Using Dynamic Susceptibility Contrast MRI in Glioblastoma Patients.

OBJECTIVES: This study evaluates the repeatability of brain perfusion using dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) with a variety of post-processing methods. METHODS: Thirty-two patients with newly diagnosed glioblastoma were recruited. On a 3-T MRI using a dual-echo, gradient-echo spin-echo DSC-MRI protocol, the patients were scanned twice 1 to 5 days apart. Perfusion maps including cerebral blood volume (CBV) and cerebral blood flow (CBF) were generated using two contrast agent leakage correction methods, along with testing normalization to reference tissue, and application of arterial input function (AIF). Repeatability of CBV and CBF within tumor regions and healthy tissues, identified by structural images, was assessed with intra-class correlation coefficients (ICCs) and repeatability coefficients (RCs). Coefficients of variation (CVs) were reported for selected methods. RESULTS: CBV and CBF were highly repeatable within tumor with ICC values up to 0.97. However, both CBV and CBF showed lower ICCs for healthy cortical tissues (up to 0.83), healthy gray matter (up to 0.95), and healthy white matter (WM; up to 0.93). The values of CV ranged from 6% to 10% in tumor and 3% to 11% in healthy tissues. The values of RC relative to the mean value of measurement within healthy WM ranged from 22% to 42% in tumor and 7% to 43% in healthy tissues. These percentages show how much variation in perfusion parameter, relative to that in healthy WM, we expect to observe to consider it statistically significant. We also found that normalization improved repeatability, but AIF deconvolution did not. CONCLUSIONS: DSC-MRI is highly repeatable in high-grade glioma patients.

Simple and reproducible linear measurements to determine ventricular enlargement in adults.

BACKGROUND: Recent studies have suggested that Evan's Index (EI) is not accurate and instead endorse volumetric measurements. Our aim was to evaluate the reproducibility of linear measurements and their correlation to ventricular volume. METHODS: Using magnetic resonance (MR) images of 30 patients referred for normal pressure hydrocephalus (NPH), EI, frontal-occipital horn ratio (FOR), third ventricular width and height, frontal horn width (FHW), and callosal angle (CA) at the foramen of Monro and the posterior commissure (PC) were independently measured by residents in neurosurgery and radiology, a neurosurgeon and radiologist, and a medical student. Intraclass correlation coefficients (ICC) were calculated to establish inter-rater agreement among the reviewers. Pearson's correlation coefficients were done to assess the relationship of the linear measurements with total ventricular volume. Kappa analyses were performed to assess the degree of agreement between cutpoints determined by the ROC analysis for the linear measurements and reviewers' gestalt impression about ventricular size with volumetric abnormality. RESULTS: The overall inter-rater agreement among reviewers was almost perfect for EI (ICC = 0.913), FOR (ICC = 0.830), third ventricular width, FHW (ICC = 0.88), and CA at PC (ICC = 0.865), substantial for temporal horn width (ICC = 0.729) and CA at foramen of Monro (ICC = 0.779), and moderate for third ventricular height (ICC = 0.496). EI, FOR, third ventricular width, temporal horn width, and CA at PC measures correlated with total ventricular volume. There was fair-to-almost-perfect agreement of the individual reviewer's gestalt responses of abnormatility with volumetric abnormality. Gestalt responses were better for more senior raters. CONCLUSION: Linear measurements are reliable and reproducible methods for determining ventricular enlargement.

Degree of corticospinal tract damage correlates with motor function after stroke.

OBJECTIVES: Direct injury to the corticospinal tract (CST) is a major factor defining motor impairment after stroke. Diffusion tensor imaging (DTI) tractography allows definition of the CST. We sought to determine whether DTI-based assessment of the degree of CST damage correlates with motor impairment at each phase of ischemic stroke. METHODS: We evaluated patients at the acute (3-7 days), subacute (30 days), and chronic (90 days) phases of ischemic stroke with DTI and clinical motor scores (upper extremity Fugl-Myer test [UE-FM], motor items of the National Institutes of Health Stroke Scale [mNIHSS]). The CST was identified and virtual fiber numbers (FN) were calculated for the affected and contralateral CST. We used Spearman correlation to study the relationship of FN ratio (FNr) (affected/unaffected CST) with motor scores at each time point, and the regression model to study the association of the acute parameters with chronic motor scores. RESULTS: We studied 23 patients. Mean age was 66.7 (±12) years. FNr correlated with UE-FM score in the acute (r = 0.50, P = 0.032), subacute (r = 0.57, P = 0.007), and chronic (r = 0.67, P = 0.0008) phase, and with mNIHSS in the acute (r = -0.48, P = 0.043), subacute (r = -0.58, P = 0.006), and chronic (r = -0.75, P = 0.0001) phase. The combination of acute NIHSS and FNr significantly predicted chronic UE-FM score (r = 0.74, P = 0.0001). INTERPRETATION: DTI-defined degree of CST injury correlates with motor impairment at each phase of ischemic stroke. The combination of baseline FNr and NIHSS predicts motor outcome. DTI-derived CST assessment could become a surrogate marker of motor impairment in the design of neurorestorative clinical trials.

MRI upsampling using feature-based nonlocal means approach.

In magnetic resonance imaging (MRI), spatial resolution is limited by several factors such as acquisition time, short physiological phenomena, and organ motion. The acquired image usually has higher resolution in two dimensions (the acquisition plane) in comparison with the third dimension, resulting in highly anisotropic voxel size. Interpolation of these low resolution (LR) images using standard techniques, such as linear or spline interpolation, results in distorted edges in the planes perpendicular to the acquisition plane. This poses limitation on conducting quantitative analyses of LR images, particularly on their voxel-wise analysis and registration. We have proposed a new non-local means feature-based technique that uses structural information of a high resolution (HR) image with a different contrast and interpolates the LR image. In this approach, the similarity between voxels is estimated using a feature vector that characterizes the laminar pattern of the brain structures, resulting in a more accurate similarity measure in comparison with conventional patch-based approach. This technique can be applied to LR images with both anisotropic and isotropic voxel sizes. Experimental results conducted on brain MRI scans of patients with brain tumors, multiple sclerosis, epilepsy, as well as schizophrenic patients and normal controls show that the proposed method is more accurate, requires fewer computations, and thus is significantly faster than a previous state-of-the-art patch-based technique. We also show how the proposed method may be used to upsample regions of interest drawn on LR images.

Lateralization of temporal lobe epilepsy using a novel uncertainty analysis of MR diffusion in hippocampus, cingulum, and fornix, and hippocampal volume and FLAIR intensity.

PURPOSE: To analyze the utility of a quantitative uncertainty analysis approach for evaluation and comparison of various MRI findings for the lateralization of epileptogenicity in mesial temporal lobe epilepsy (mTLE), including novel diffusion-based analyses. METHODS: We estimated the hemispheric variation uncertainty (HVU) of hippocampal T1 volumetry and FLAIR (Fluid Attenuated Inversion Recovery) intensity. Using diffusion tensor images of 23 nonepileptic subjects, we estimated the HVU levels of mean diffusivity (MD) in the hippocampus, and fractional anisotropy (FA) in the posteroinferior cingulum and crus of fornix. Imaging from a retrospective cohort of 20 TLE patients who had undergone surgical resection with Engel class I outcomes was analyzed to determine whether asymmetry of preoperative volumetrics, FLAIR intensities, and MD values in hippocampi, as well as FA values in posteroinferior cingula and fornix crura correctly predicted laterality of seizure onset. Ten of the cohort had pathologically proven mesial temporal sclerosis (MTS). Seven of these patients had undergone extraoperative electrocorticography (ECoG) for lateralization or to rule out extra-temporal foci. RESULTS: HVU was estimated to be 3.1×10(-5) for hippocampal MD, 0.027 for FA in posteroinferior cingulum, 0.018 for FA in crus of fornix, 0.069 for hippocampal normalized volume, and 0.099 for hippocampal normalized FLAIR intensity. Using HVU analysis, a higher hippocampal MD value, lower FA within the posteroinferior cingulum and crus of fornix, shrinkage in hippocampal volume, and higher hippocampal FLAIR intensity were observed beyond uncertainty on the side ipsilateral to seizure onset for 10, 10, 9, 9, and 10 out of 10 pathology-proven MTS patients, respectively. Considering all 20 TLE patients, these numbers were 18, 15, 14, 13, and 16, respectively. However, consolidating the lateralization results of HVU analysis on these quantities by majority voting has detected the epileptogenic side for 19 out of 20 cases with no wrong lateralization. CONCLUSION: The presence of MTS in TLE patients is associated with an elevated MD value in the ipsilateral hippocampus and a reduced FA value in the posteroinferior subregion of the ipsilateral cingulum and crus of ipsilateral fornix. When considering all TLE patients, among the mentioned biomarkers the hippocampal MD had the best performance with true detection rate of 90% without any wrong lateralization. The proposed uncertainty based analyses hold promise for improving decision-making for surgical resection.

Perfusion and Diffusion Abnormalities of Multiple Sclerosis Lesions and Relevance of Classified Lesions to Disease Status.

OBJECTIVE: Hemodynamic abnormality and disruption of white matter (WM) integrity are significant components in the pathophysiology of multiple sclerosis (MS) lesions. However, the roles of stratified lesions with distinct degrees of hemodynamic and structural injury in disease states remain to be explored. We tested the hypothesis that hemodynamic and structural impairment, as assessed by cerebral blood volume (CBV) and fractional anisotropy (FA), respectively, characterizes the extent of tissue injury, and the load of lesion with substantial tissue destruction would reflect the disease status and therefore, would be related to clinical disability. METHODS: Seven relapsing-remitting MS patients and seven healthy controls underwent perfusion, diffusion and conventional MRI scans. Based on T2-FLAIR and T1-weighted image, WM plaques were classified. After image coregistration, values of CBV and FA were estimated in three distinct lesion types (active, T1-hypointense and T1-isointense lesion) and compared with those obtained in WM from controls. A total of 1135 lesions were evaluated. Brain volumetric measurement and correlative analysis between brain atrophy, lesion volume and clinical disability were also performed. RESULTS: Compared with normal WM, significantly reduced CBV and FA were present in the T1-hypointense lesion, while insignificant changes in both parameters were exhibited in the T1-isointense lesion. However, increased CBV but significantly decreased FA was detected in the active lesion. A close spatial relationship between active and T1-hypointense lesion was observed. Lesion load represented by T1-hypointense plus active lesion volume significantly correlated with brain atrophy, which, in turn, significantly correlated with the severity of clinical disability. CONCLUSION: A distinct combination of CBV and FA characterizes the status of a specific lesion type. A severe structural impairment does not solely occur in the T1-hypointense lesion, but is also associated with the active lesion. The burden of the lesion with extensive structural damage provides an image index, indicative of disease status.

Slice accelerated gradient-echo spin-echo dynamic susceptibility contrast imaging with blipped CAIPI for increased slice coverage.

PURPOSE: To improve slice coverage of gradient echo spin echo (GESE) sequences for dynamic susceptibility contrast (DSC) MRI using a simultaneous-multiple-slice (SMS) method. METHODS: Data were acquired on 3 Tesla (T) MR scanners with a 32-channel head coil. To evaluate use of SMS for DSC, an SMS GESE sequence with two-fold slice coverage and same temporal sampling was compared with a standard GESE sequence, both with 2× in-plane acceleration. A signal to noise ratio (SNR) comparison was performed on one healthy subject. Additionally, data with Gadolinium injection were collected on three patients with glioblastoma using both sequences, and perfusion analysis was performed on healthy tissues as well as on tumor. RESULTS: Retained SNR of SMS DSC is 90% for a gradient echo (GE) and 99% for a spin echo (SE) acquisition, compared with a standard acquisition without slice acceleration. Comparing cerebral blood volume maps, it was observed that the results of standard and SMS acquisitions are comparable for both GE and SE images. CONCLUSION: Two-fold slice accelerated DSC MRI achieves similar SNR and perfusion metrics as a standard acquisition, while allowing a significant increase in slice coverage of the brain. The results also point to a possibility to improve temporal sampling rate, while retaining the same slice coverage.

Lateralization of temporal lobe epilepsy by imaging-based response-driven multinomial multivariate models.

We have developed response-driven multinomial models, based on multivariate imaging features, to lateralize the epileptogenicity in temporal lobe epilepsy (TLE) patients. To this end, volumetrics and statistical quantities of FLAIR intensity and normalized ictal-interictal SPECT intensity on left and right hippocampi were extracted from preoperative images of forty-five retrospective TLE patients with surgical outcome of Engel class l. Using multinomial logistic function regression, the parameters of various univariate and multivariate models were estimated. Among univariate response models, the response model with SPECT attributes and response model with mean FLAIR attributes achieved the lowest fit deviance (65.1±0.2 and 65.5±0.3, respectively). They resulted in the highest probability of detection (0.82) and lowest probability of false alarm (0.02) for the epileptogenic side. The multivariate response model with incorporating all volumetrics, mean and standard deviation FLAIR, and SPECT attributes achieved a significantly lower fit deviance than other response models (11.9±0.1, p <; 0.001). It reached probability of detection of 1 with no false alarms. We were able to correctly lateralize the fifteen TLE patients who had undergone phase II intracranial monitoring. Therefore, the phase II intracranial monitoring might have been avoided for this set of patients. Based on this lateralization response model, the side of epileptogenicity was also detected for all thirty patients who had preceded to resection with only phase I of EEG monitoring. In conclusion, the proposed multinomial multivariate response-driven model for lateralization of epileptogenicity in TLE patients can help in decision-making prior to surgical resection and may reduce the need for implantation of intracranial monitoring electrodes.

Analysis of scalp EEG and quantitative MRI in cases of temporal lobe epilepsy requiring intracranial electrographic monitoring.

Abstract Purpose. Contradictory scalp electroencephalographic (sEEG) and discordant imaging features are common in temporal lobe epilepsy (TLE). We assessed the relative importance of sEEG features and their relation to quantitative magnetic resonance (MR) imaging measures in regard to surgical outcome. Methods and materials. Patients with a putative TLE underwent extraoperative electrocorticography (eECoG) with bitemporal subdural electrodes for clarification of the ictogenic source. Patients were categorized by sEEG ictal patterns (IPs) as showing unilateral or bilateral onset. Concordance with the side of resection, as determined by eECoG, to that suggested by the predominant sEEG IP was further analysed as: (a) entirely ipsilateral eECoG IPs with discordant nonelectrographic data; (b) ipsilateral preponderant (> 80%) eECoG IPs; and c) contralateral preponderant (> 80%) eECoG IPs. Quantitative hippocampal volumes and signal characteristics were applied for comparison. Results. Of 26 patients, eECoG confirmed a unilateral IP on sEEG in 19 (73%). Of these 19, exclusively ipsilateral sEEG interical epileptiform discharges (IEDs) were identified in 9 (47%). When bilateral, generalized, absent or contralateral IEDs were found, 6 cases (60%) still showed a preponderantly ipsilateral IP identifying the epileptogenic side. In patients with sEEG bilateral IPs, 5 (71%) also had bilateral IEDs. Of the 16 patients who underwent resection, 14 (87.5%) achieved favourable outcomes and 9 (56%), seizure cessation. Hippocampal volumetry in 23 patients correctly lateralized 7 (30%) whereas fluid-attenuated inversion recovery (FLAIR) signal measures applied in 23 patients lateralized 9 (39%). Conclusions. Favourable surgical outcomes are attainable following eECoG in cases where ambiguity exists regarding the laterality of TLE on sEEG, even for those in whom bilateral IPs and either bilateral or no IEDs are demonstrated on sEEG. Neither volumetric nor FLAIR signal ratios were sufficiently reliable for lateralizing TLE in the majority of cases.