Dental-dedicated MRI, a novel approach for dentomaxillofacial diagnostic imaging: technical specifications and feasibility.

MRI is a noninvasive, ionizing radiation-free imaging modality that has become an indispensable medical diagnostic method. The literature suggests MRI as a potential diagnostic modality in dentomaxillofacial radiology. However, current MRI equipment is designed for medical imaging (eg, brain and body imaging), with general-purpose use in radiology. Hence, it appears expensive for dentists to purchase and maintain, besides being complex to operate. In recent years, MRI has entered some areas of dentistry and has reached a point in which it can be provided following a tailored approach. This technical report introduces a dental-dedicated MRI (ddMRI) system, describing how MRI can be adapted to fit dentomaxillofacial radiology through the appropriate choice of field strength, dental radiofrequency surface coil, and pulse sequences. Also, this technical report illustrates the possible application and feasibility of the suggested ddMRI system in some relevant diagnostic tasks in dentistry. Based on the presented cases, it is fair to consider the suggested ddMRI system as a feasible approach to introducing MRI to dentists and dentomaxillofacial radiology specialists. Further studies are needed to clarify the diagnostic accuracy of ddMRI considering the various diagnostic tasks relevant to the practice of dentistry.

Evolution of Cortical and White Matter Lesion Load in Early-Stage Multiple Sclerosis: Correlation With Neuroaxonal Damage and Clinical Changes.

Introduction: Changes in cortical and white matter lesion (CL, WML) load are pivotal metrics to diagnose and monitor multiple sclerosis patients. Yet, the relationship between (i) changes in CL/WML load and disease progression and between (ii) changes in CL/WML load and neurodegeneration at early MS stages is not yet established. In this work, we have assessed the hypothesis that the combined CL and WML load as well as their 2-years evolution are surrogate markers of neurodegeneration and clinical progression at early MS stages. To achieve this goal, we have studied a group of RRMS patients and have investigated the impact of both CL and WML load on neuroaxonal damage as measured by serum neurofilament light chain (sNfL). Next, we have explored whether changes in CL/WML load over 2 years in the same cohort of early-MS are related to motor and cognitive changes. Methods: Thirty-two RRMS patients (<5 years disease duration) underwent: (i) 3T MRI for CL/WML detection and clinical assessment at baseline and 2-years follow-up; and (ii) baseline blood test for sNfL. The correlation between the number and volume of CL/WML and sNfL was assessed by using the Spearman's rank correlation coefficient and a generalized linear model (GLM). A GLM was also used to assess the relationship between (i) the number/volume of new, enlarged, resolved, shrunken, stable lesions and (ii) the difference in clinical scores between two time-points. Results: At baseline, sNfL levels correlated with both total CL count/volume (ρ = 0.6/0.7, Corr-P <0.017/Corr-P < 0.001) and with total WML count/volume (ρ = 0.6/0.6, Corr-P < 0.01 for both). Baseline sNfL levels also correlated with new WML count/volume (ρ = 0.6/0.5, Corr-P < 0.01/Corr-P < 0.05) but not with new CL. Longitudinal changes in CL and WML count and volume were significantly associated with (i) sustained attention, auditory information, processing speed and flexibility (p < 0.01), (ii) verbal memory (p < 0.01); (iii) verbal fluency (p < 0.05); and (iv) hand-motor function (p < 0.05). Discussion: Changes in cortical and white matter focal damage in early MS patients correlate with global neuroaxonal damage and is associated to cognitive performances.

Fast model-based T2 mapping using SAR-reduced simultaneous multislice excitation.

PURPOSE: To obtain whole-brain high-resolution T2 maps in 2 minutes by combining simultaneous multislice excitation and low-power PINS (power independent of number of slices) refocusing pulses with undersampling and a model-based reconstruction. METHODS: A multi-echo spin-echo sequence was modified to acquire multiple slices simultaneously, ensuring low specific absorption rate requirements. In addition, the acquisition was undersampled to achieve further acceleration. Data were reconstructed by subsequently applying parallel imaging to separate signals from different slices, and a model-based reconstruction to estimate quantitative T2 from the undersampled data. The signal model used is based on extended phase graph simulations that also account for nonideal slice profiles and B1 inhomogeneity. In vivo experiments with 3 healthy subjects were performed to compare accelerated T2 maps to fully sampled single-slice acquisitions. The accuracy of the T2 values was assessed with phantom experiments by comparing the T2 values to single-echo spin-echo measurements. RESULTS: In vivo results showed that conventional multi-echo spin-echo, simultaneous multislice, and undersampling result in similar mean T2 values within regions of interest. However, combining simultaneous multislice and undersampling results in higher SDs (about 7 ms) in comparison to a conventional sequence (about 3 ms). The T2 values were reproducible between scan and rescan (SD < 1.2 ms) within subjects and were in similar ranges across subjects (SD < 4.5 ms). CONCLUSION: The proposed method is a fast T2 mapping technique that enables whole-brain acquisitions at 0.7-mm in-plane resolution, 3-mm slice thickness, and low specific absorption rate in 2 minutes.

Partial volume-aware assessment of multiple sclerosis lesions.

White-matter lesion count and volume estimation are key to the diagnosis and monitoring of multiple sclerosis (MS). Automated MS lesion segmentation methods that have been proposed in the past 20 years reach their limits when applied to patients in early disease stages characterized by low lesion load and small lesions. We propose an algorithm to automatically assess MS lesion load (number and volume) while taking into account the mixing of healthy and lesional tissue in the image voxels due to partial volume effects. The proposed method works on 3D MPRAGE and 3D FLAIR images as obtained from current routine MS clinical protocols. The method was evaluated and compared with manual segmentation on a cohort of 39 early-stage MS patients with low disability, and showed higher Dice similarity coefficients (median DSC = 0.55) and higher detection rate (median DR = 61%) than two widely used methods (median DSC = 0.50, median DR < 45%) for automated MS lesion segmentation. We argue that this is due to the higher performance in segmentation of small lesions, which are inherently prone to partial volume effects.

Accelerated T2 mapping combining parallel MRI and model-based reconstruction: GRAPPATINI.

BACKGROUND: Quantitative T2 measurements are sensitive to intra- and extracellular water accumulation and myelin loss. Therefore, quantitative T2 promises to be a good biomarker of disease. However, T2 measurements require long acquisition times. PURPOSE: To accelerate T2 quantification and subsequent generation of synthetic T2 -weighted (T2 -w) image contrast for clinical research and routine. To that end, a recently developed model-based approach for rapid T2 and M0 quantification (MARTINI) based on undersampling k-space, was extended by parallel imaging (GRAPPA) to enable high-resolution T2 mapping with access to T2 -w images in less than 2 minutes acquisition time for the entire brain. STUDY TYPE: Prospective cross-sectional study. SUBJECTS/PHANTOM: Fourteen healthy subjects and a multipurpose phantom. FIELD STRENGTH/SEQUENCE: Carr-Purcell-Meiboom-Gill sequence at a 3T scanner. ASSESSMENT: The accuracy and reproducibility of the accelerated T2 quantification was assessed. Validations comprised MRI studies on a phantom as well as the brain, knee, prostate, and liver from healthy volunteers. Synthetic T2 -w images were generated from computed T2 and M0 maps and compared to conventional fast spin-echo (SE) images. STATISTICAL TESTS: Root mean square distance (RMSD) to the reference method and region of interest analysis. RESULTS: The combination of MARTINI and GRAPPA (GRAPPATINI) lead to a 10-fold accelerated T2 mapping protocol with 1:44 minutes acquisition time and full brain coverage. The RMSD of GRAPPATINI increases less (4.3%) than a 10-fold MARTINI reconstruction (37.6%) in comparison to the reference. Reproducibility tests showed low standard deviation (SD) of T2 values in regions of interest between scan and rescan (<0.4 msec) and across subjects (<4 msec). DATA CONCLUSION: GRAPPATINI provides highly reproducible and fast whole-brain T2 maps and arbitrary synthetic T2 -w images in clinically compatible acquisition times of less than 2 minutes. These abilities are expected to support more widespread clinical applications of quantitative T2 mapping. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2018;48:359-368.

Surface-based characteristics of the cerebellar cortex visualized with ultra-high field MRI.

Although having a relatively homogeneous cytoarchitectonic organization, the cerebellar cortex is a heterogeneous region characterized by different amounts of myelin, iron and protein expression profiles. In this study, we used quantitative T1 and T2* mapping at ultra-high field (7T) MRI to investigate the tissue characteristics of the cerebellar gray matter surface and its layers. Detailed subject-specific surfaces were generated at three different cortical depths and averaged across subjects to create averaged T1- and T2*-maps on the cerebellar surface. T1 surfaces showed an alternation of lower and higher T1 values when going from the median to the lateral part of the cerebellar hemispheres. In addition, longer T1 values were observed in the more superficial gray matter layers. T2*-maps showed a similar longitudinal pattern, but no change related to the cortical depths. These patterns are possibly due to variations in the level of myelination, iron and zebrin protein expression.

True constructive interference in the steady state (trueCISS).

PURPOSE: To introduce a novel time-efficient method, termed true constructive interference in the steady state (trueCISS), that not only solves the problem of banding artifacts for balanced steady-state free precession (bSSFP) but also provides its genuine, that is, true, on-resonant signal. METHODS: After a compressed sensing reconstruction from a set of highly undersampled phase-cycled bSSFP scans, the local off-resonance, relaxation time ratio, and equilibrium magnetization are voxel-wise estimated using a dictionary-based fitting routine. Subsequently, on-resonant bSSFP images are generated using the previously estimated parameters. Due to the high undersampling factors used, the acquisition time is not prolonged with respect to a standard CISS acquisition. RESULTS: From a set of 16 phase-cycled SSFP scans in combination with an eightfold undersampling, both phantom and in vivo whole-brain experiments demonstrate that banding successfully can be removed. Additionally, trueCISS allows the derivation of synthetic bSSFP images with arbitrary flip angles, which enables image contrasts that may not be possible to acquire in practice due to safety constraints. CONCLUSION: TrueCISS offers banding-free bSSFP images with on-resonant signal intensity and without requiring additional acquisition time compared to conventional methods. Magn Reson Med 79:1901-1910, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

The Combined Quantification and Interpretation of Multiple Quantitative Magnetic Resonance Imaging Metrics Enlightens Longitudinal Changes Compatible with Brain Repair in Relapsing-Remitting Multiple Sclerosis Patients.

OBJECTIVE: Quantitative and semi-quantitative MRI (qMRI) metrics provide complementary specificity and differential sensitivity to pathological brain changes compatible with brain inflammation, degeneration, and repair. Moreover, advanced magnetic resonance imaging (MRI) metrics with overlapping elements amplify the true tissue-related information and limit measurement noise. In this work, we combined multiple advanced MRI parameters to assess focal and diffuse brain changes over 2 years in a group of early-stage relapsing-remitting MS patients. METHODS: Thirty relapsing-remitting MS patients with less than 5 years disease duration and nine healthy subjects underwent 3T MRI at baseline and after 2 years including T1, T2, T2* relaxometry, and magnetization transfer imaging. To assess longitudinal changes in normal-appearing (NA) tissue and lesions, we used analyses of variance and Bonferroni correction for multiple comparisons. Multivariate linear regression was used to assess the correlation between clinical outcome and multiparametric MRI changes in lesions and NA tissue. RESULTS: In patients, we measured a significant longitudinal decrease of mean T2 relaxation times in NA white matter (p = 0.005) and a decrease of T1 relaxation times in the pallidum (p < 0.05), which are compatible with edema reabsorption and/or iron deposition. No longitudinal changes in qMRI metrics were observed in controls. In MS lesions, we measured a decrease in T1 relaxation time (p-value < 2.2e-16) and a significant increase in MTR (p-value < 1e-6), suggesting repair mechanisms, such as remyelination, increased axonal density, and/or a gliosis. Last, the evolution of advanced MRI metrics-and not changes in lesions or brain volume-were correlated to motor and cognitive tests scores evolution (Adj-R2 > 0.4, p < 0.05). In summary, the combination of multiple advanced MRI provided evidence of changes compatible with focal and diffuse brain repair at early MS stages as suggested by histopathological studies.

Rivastigmine decreases brain damage in HIV patients with mild cognitive deficits.

Rivastigmine has been shown to improve cognition in HIV+ patients with minor neurocognitive disorders; however, the mechanisms underlying such beneficial effect are currently unknown. To assess whether rivastigmine therapy is associated with decreased brain inflammation and damage, we performed T1/T2* relaxometry and magnetization transfer imaging in 17 aviremic HIV+ patients with minor neurocognitive disorders enrolled on a crossed over randomized rivastigmine trial. Rivastigmine therapy was associated with changes in MRI metrics indicating a decrease in brain water content (i.e., edema reabsorption) and/or reduced demyelination/axonal damage. Furthermore, MRI changes correlated with cognitive improvement on rivastigmine therapy.

Prospective head motion correction using FID-guided on-demand image navigators.

PURPOSE: We suggest a motion correction concept that employs free-induction-decay (FID) navigator signals to continuously monitor motion and to guide the acquisition of image navigators for prospective motion correction following motion detection. METHODS: Motion causes out-of-range signal changes in FID time series that, and in this approach, initiate the acquisition of an image navigator. Co-registration of the image navigator to a reference provides rigid-body-motion parameters to facilitate prospective motion correction. Both FID and image navigator are integrated into a prototype magnetization-prepared rapid gradient-echo (MPRAGE) sequence. The performance of the method is investigated using image quality metrics and the consistency of brain volume measurements. RESULTS: Ten healthy subjects were scanned (a) while performing head movements (nodding, shaking, and moving in z-direction) and (b) to assess the co-registration performance. Mean absolute errors of 0.27 ± 0.38 mm and 0.19 ± 0.24° for translation and rotation parameters were measured. Image quality was qualitatively improved after correction. Significant improvements were observed in automated image quality measures and for most quantitative brain volume computations after correction. CONCLUSION: The presented method provides high sensitivity to detect head motion while minimizing the time invested in acquiring navigator images. Limits of this implementation arise from temporal resolution to detect motion, false-positive alarms, and registration accuracy. Magn Reson Med 78:193-203, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

An Ultra-High Field Study of Cerebellar Pathology in Early Relapsing-Remitting Multiple Sclerosis Using MP2RAGE.

OBJECTIVES: The aim of this study was to study focal cerebellar pathology in early stages of multiple sclerosis (MS) using ultra-high-field magnetization-prepared 2 inversion-contrast rapid gradient-echo (7T MP2RAGE). MATERIALS AND METHODS: Twenty early-stage relapsing-remitting MS patients underwent an MP2RAGE acquisition at 7 T magnetic resonance imaging (MRI) (images acquired at 2 different resolutions: 0.58 × 0.58 × 0.58 mm, 7T_0.58, and 0.75 × 0.75 × 0.90 mm, 7T_0.75) and 3 T MRI (1.0 × 1.0 × 1.2 mm, 3T_1.0). Total cerebellar lesion load and volume and mean cerebellar lesion volume were compared across images using a Wilcoxon signed-rank test. Mean T1 relaxation times in lesions and normal-appearing tissue as well as contrast-to-noise ratio (CNR) measurements were also compared using a Wilcoxon signed-rank test. A multivariate analysis was applied to assess the contribution of MRI metrics to clinical performance in MS patients. RESULTS: Both 7T_0.58 and 7T_0.75 MP2RAGE showed significantly higher lesion load compared with 3T_1.0 MP2RAGE (P < 0.001). Plaques that were judged as leukocortical in 7T_0.75 and 3T_1.0 MP2RAGEs were instead identified as WM lesions in 7T_0.58 MP2RAGE. Cortical lesion CNR was significantly higher in MP2RAGEs at 7 T than at 3 T. Total lesion load as well as total and mean lesion volume obtained at both 7 T and 3 T MP2RAGE significantly predicted attention (P < 0.05, adjusted R = 0.5), verbal fluency (P < 0.01, adjusted R = 0.6), and motor performance (P = 0.01, adjusted R = 0.7). CONCLUSIONS: This study demonstrates the value of 7 T MP2RAGE to study the cerebellum in early MS patients. 7T_0.58 MP2RAGE provides a more accurate anatomical description of white and gray matter pathology compared with 7T_0.75 and 3T_1.0 MP2RAGE, likely due to the improved spatial resolution, lower partial volume effects, and higher CNR.

Basic MR sequence parameters systematically bias automated brain volume estimation.

INTRODUCTION: Automated brain MRI morphometry, including hippocampal volumetry for Alzheimer disease, is increasingly recognized as a biomarker. Consequently, a rapidly increasing number of software tools have become available. We tested whether modifications of simple MR protocol parameters typically used in clinical routine systematically bias automated brain MRI segmentation results. METHODS: The study was approved by the local ethical committee and included 20 consecutive patients (13 females, mean age 75.8 ± 13.8 years) undergoing clinical brain MRI at 1.5 T for workup of cognitive decline. We compared three 3D T1 magnetization prepared rapid gradient echo (MPRAGE) sequences with the following parameter settings: ADNI-2 1.2 mm iso-voxel, no image filtering, LOCAL- 1.0 mm iso-voxel no image filtering, LOCAL+ 1.0 mm iso-voxel with image edge enhancement. Brain segmentation was performed by two different and established analysis tools, FreeSurfer and MorphoBox, using standard parameters. RESULTS: Spatial resolution (1.0 versus 1.2 mm iso-voxel) and modification in contrast resulted in relative estimated volume difference of up to 4.28 % (p < 0.001) in cortical gray matter and 4.16 % (p < 0.01) in hippocampus. Image data filtering resulted in estimated volume difference of up to 5.48 % (p < 0.05) in cortical gray matter. CONCLUSION: A simple change of MR parameters, notably spatial resolution, contrast, and filtering, may systematically bias results of automated brain MRI morphometry of up to 4-5 %. This is in the same range as early disease-related brain volume alterations, for example, in Alzheimer disease. Automated brain segmentation software packages should therefore require strict MR parameter selection or include compensatory algorithms to avoid MR parameter-related bias of brain morphometry results.

Ensemble average propagator-based detection of microstructural alterations after stroke.

PURPOSE: New analytical reconstruction techniques of diffusion weighted signal have been proposed. A previous work evidenced the exploitability of some indices derived from the simple harmonic oscillator-based reconstruction and estimation (3D-SHORE) model as numerical biomarkers of neural plasticity after stroke. Here, the analysis is extended to two additional indices: return to the plane/origin (RTPP/RTOP) probabilities. Moreover, several motor networks were introduced and the results were analyzed at different time scales. METHODS: Ten patients underwent three diffusion spectrum imaging (DSI) scans [1 week (tp1), 1 month (tp2) and 6 months (tp3) after stroke]. Ten matched controls underwent two DSI scans 1 month apart. 3D-SHORE was used for reconstructing the signal and the microstructural indices were derived. Tract-based analysis was performed along motor cortical, subcortical and transcallosal networks in the contralesional area. RESULTS: The optimal intra-class correlation coefficient (ICC) was obtained in the subcortical loop for propagator anisotropy (ICC [Formula: see text] 0.96), followed by generalized fractional anisotropy (ICC [Formula: see text] 0.94). The new indices reached the highest stability in the transcallosal network and performed well in the cortical and subcortical networks with the exception of RTOP in the cortical loop (ICC [Formula: see text] 0.59). They allowed discriminating patients from controls at the majority of the timescales. Finally, the regression model using indices calculated along the subcortical loop at tp1 resulted in the best prediction of clinical outcome. CONCLUSIONS: The whole set of microstructural indices provide measurements featuring high precision. The new indices allow discriminating patients from controls in all networks, except for RTPP in the cortical loop. Moreover, the 3D-SHORE indices in subcortical connections constitute a good regression model for predicting the clinical outcome at 6 months, supporting their suitability as numerical biomarkers for neuronal plasticity after stroke.

A New Approach for Deep Gray Matter Analysis Using Partial-Volume Estimation.

INTRODUCTION: The existence of partial volume effects in brain MR images makes it challenging to understand physio-pathological alterations underlying signal changes due to pathology across groups of healthy subjects and patients. In this study, we implement a new approach to disentangle gray and white matter alterations in the thalamus and the basal ganglia. The proposed method was applied to a cohort of early multiple sclerosis (MS) patients and healthy subjects to evaluate tissue-specific alterations related to diffuse inflammatory or neurodegenerative processes. METHOD: Forty-three relapsing-remitting MS patients and nineteen healthy controls underwent 3T MRI including: (i) fluid-attenuated inversion recovery, double inversion recovery, magnetization-prepared gradient echo for lesion count, and (ii) T1 relaxometry. We applied a partial volume estimation algorithm to T1 relaxometry maps to gray and white matter local concentrations as well as T1 values characteristic of gray and white matter in the thalamus and the basal ganglia. Statistical tests were performed to compare groups in terms of both global T1 values, tissue characteristic T1 values, and tissue concentrations. RESULTS: Significant increases in global T1 values were observed in the thalamus (p = 0.038) and the putamen (p = 0.026) in RRMS patients compared to HC. In the Thalamus, the T1 increase was associated with a significant increase in gray matter characteristic T1 (p = 0.0016) with no significant effect in white matter. CONCLUSION: The presented methodology provides additional information to standard MR signal averaging approaches that holds promise to identify the presence and nature of diffuse pathology in neuro-inflammatory and neurodegenerative diseases.

White Matter MS-Lesion Segmentation Using a Geometric Brain Model.

Brain magnetic resonance imaging (MRI) in patients with Multiple Sclerosis (MS) shows regions of signal abnormalities, named plaques or lesions. The spatial lesion distribution plays a major role for MS diagnosis. In this paper we present a 3D MS-lesion segmentation method based on an adaptive geometric brain model. We model the topological properties of the lesions and brain tissues in order to constrain the lesion segmentation to the white matter. As a result, the method is independent of an MRI atlas. We tested our method on the MICCAI MS grand challenge proposed in 2008 and achieved competitive results. In addition, we used an in-house dataset of 15 MS patients, for which we achieved best results in most distances in comparison to atlas based methods. Besides classical segmentation distances, we motivate and formulate a new distance to evaluate the quality of the lesion segmentation, while being robust with respect to minor inconsistencies at the boundary level of the ground truth annotation.

Serum neurofilament light chain in early relapsing remitting MS is increased and correlates with CSF levels and with MRI measures of disease severity.

BACKGROUND/OBJECTIVES: Neurofilament light chain (NfL) levels in the cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients correlate with the degree of neuronal injury. To date, little is known about NfL concentrations in the serum of relapsing remitting multiple sclerosis (RRMS) patients and their relationship with CSF levels and magnetic resonance imaging (MRI) measures of disease severity. We aimed to validate the quantification of NfL in serum samples of RRMS, as a biofluid source easily accessible for longitudinal studies. METHODS: A total of 31 RRMS patients underwent CSF and serum sampling. After a median time of 3.6 years, 19 of these RRMS patients, 10 newly recruited RRMS patients and 18 healthy controls had a 3T MRI and serum sampling. NfL concentrations were determined by electrochemiluminescence immunoassay. RESULTS: NfL levels in serum were highly correlated to levels in CSF (r = 0.62, p = 0.0002). Concentrations in serum were higher in patients than in controls at baseline (p = 0.004) and follow-up (p = 0.0009) and did not change over time (p = 0.56). Serum NfL levels correlated with white matter (WM) lesion volume (r = 0.68, p < 0.0001), mean T1 (r = 0.40, p = 0.034) and T2* relaxation time (r = 0.49, p = 0.007) and with magnetization transfer ratio in normal appearing WM (r = -0.41, p = 0.029). CONCLUSION: CSF and serum NfL levels were highly correlated, and serum concentrations were increased in RRMS. Serum NfL levels correlated with MRI markers of WM disease severity. Our findings further support longitudinal studies of serum NfL as a potential biomarker of on-going disease progression and as a potential surrogate to quantify effects of neuroprotective drugs in clinical trials.

Comparison of accelerated T1-weighted whole-brain structural-imaging protocols.

Imaging in neuroscience, clinical research and pharmaceutical trials often employs the 3D magnetisation-prepared rapid gradient-echo (MPRAGE) sequence to obtain structural T1-weighted images with high spatial resolution of the human brain. Typical research and clinical routine MPRAGE protocols with ~1mm isotropic resolution require data acquisition time in the range of 5-10min and often use only moderate two-fold acceleration factor for parallel imaging. Recent advances in MRI hardware and acquisition methodology promise improved leverage of the MR signal and more benign artefact properties in particular when employing increased acceleration factors in clinical routine and research. In this study, we examined four variants of a four-fold-accelerated MPRAGE protocol (2D-GRAPPA, CAIPIRINHA, CAIPIRINHA elliptical, and segmented MPRAGE) and compared clinical readings, basic image quality metrics (SNR, CNR), and automated brain tissue segmentation for morphological assessments of brain structures. The results were benchmarked against a widely-used two-fold-accelerated 3T ADNI MPRAGE protocol that served as reference in this study. 22 healthy subjects (age=20-44yrs.) were imaged with all MPRAGE variants in a single session. An experienced reader rated all images of clinically useful image quality. CAIPIRINHA MPRAGE scans were perceived on average to be of identical value for reading as the reference ADNI-2 protocol. SNR and CNR measurements exhibited the theoretically expected performance at the four-fold acceleration. The results of this study demonstrate that the four-fold accelerated protocols introduce systematic biases in the segmentation results of some brain structures compared to the reference ADNI-2 protocol. Furthermore, results suggest that the increased noise levels in the accelerated protocols play an important role in introducing these biases, at least under the present study conditions.

Automated detection of white matter and cortical lesions in early stages of multiple sclerosis.

PURPOSE: To develop a method to automatically detect multiple sclerosis (MS) lesions, located both in white matter (WM) and in the cortex, in patients with low disability and early disease stage. MATERIALS AND METHODS: We developed a lesion detection method, based on the k-nearest neighbor (k-NN) technique, to detect lesions as small as 0.0036 mL. This method uses the image intensity information from up to four different 3D magnetic resonance imaging (MRI) sequences (magnetization-prepared rapid gradient-echo, MPRAGE; magnetization-prepared two inversion-contrast rapid gradient-echo, MP2RAGE; 3D fluid-attenuated inversion recovery, FLAIR; and 3D double-inversion recovery, DIR), acquired on a 3T scanner. To these intensity features we added the information obtained by the spatial coordinates and tissue prior probabilities provided by the International Consortium for Brain Mapping (ICBM). Quantitative assessment was done in 39 early-stage MS patients with a "leave-one-out" cross-validation. RESULTS: The best lesion detection rate (DR) performance in WM was obtained using MP2RAGE, FLAIR, and DIR intensities (77% for lesions ≥0.0036 mL; 85% for lesions ≥0.005 mL). Similar results were obtained excluding the DIR intensity as well as when using only MPRAGE and FLAIR (DR = 75%, P = 0.5720). However, the combination of FLAIR with DIR and MP2RAGE appeared to be the best for detecting cortical lesions (DR = 62%), compared to the other combination of sequences (P < 0.001). CONCLUSION: For WM lesion detection, similar results were observed when only conventional clinical sequences (FLAIR, MPRAGE) were used compared to a combination of conventional and "advanced" sequences (MP2RAGE, DIR). Cortical lesion detection increased significantly when "advanced" sequences were used. J. Magn. Reson. Imaging 2015. J. Magn. Reson. Imaging 2016;43:1445-1454.

Multicontrast MRI Quantification of Focal Inflammation and Degeneration in Multiple Sclerosis.

INTRODUCTION: Local microstructural pathology in multiple sclerosis patients might influence their clinical performance. This study applied multicontrast MRI to quantify inflammation and neurodegeneration in MS lesions. We explored the impact of MRI-based lesion pathology in cognition and disability. METHODS: 36 relapsing-remitting MS subjects and 18 healthy controls underwent neurological, cognitive, behavioural examinations and 3 T MRI including (i) fluid attenuated inversion recovery, double inversion recovery, and magnetization-prepared gradient echo for lesion count; (ii) T1, T2, and T2(*) relaxometry and magnetisation transfer imaging for lesion tissue characterization. Lesions were classified according to the extent of inflammation/neurodegeneration. A generalized linear model assessed the contribution of lesion groups to clinical performances. RESULTS: Four lesion groups were identified and characterized by (1) absence of significant alterations, (2) prevalent inflammation, (3) concomitant inflammation and microdegeneration, and (4) prevalent tissue loss. Groups 1, 3, 4 correlated with general disability (Adj-R (2) = 0.6; P = 0.0005), executive function (Adj-R (2) = 0.5; P = 0.004), verbal memory (Adj-R (2) = 0.4; P = 0.02), and attention (Adj-R (2) = 0.5; P = 0.002). CONCLUSION: Multicontrast MRI provides a new approach to infer in vivo histopathology of plaques. Our results support evidence that neurodegeneration is the major determinant of patients' disability and cognitive dysfunction.

Magnetic resonance imaging in Alzheimer's Disease Neuroimaging Initiative 2.

INTRODUCTION: Alzheimer's Disease Neuroimaging Initiative (ADNI) is now in its 10th year. The primary objective of the magnetic resonance imaging (MRI) core of ADNI has been to improve methods for clinical trials in Alzheimer's disease (AD) and related disorders. METHODS: We review the contributions of the MRI core from present and past cycles of ADNI (ADNI-1, -Grand Opportunity and -2). We also review plans for the future-ADNI-3. RESULTS: Contributions of the MRI core include creating standardized acquisition protocols and quality control methods; examining the effect of technical features of image acquisition and analysis on outcome metrics; deriving sample size estimates for future trials based on those outcomes; and piloting the potential utility of MR perfusion, diffusion, and functional connectivity measures in multicenter clinical trials. DISCUSSION: Over the past decade the MRI core of ADNI has fulfilled its mandate of improving methods for clinical trials in AD and will continue to do so in the future.