A comprehensive investigation of physiologic noise modeling in resting state fMRI; time shifted cardiac noise in EPI and its removal without external physiologic signal measures.

Hemodynamic cardiac and respiratory-cycle fluctuations are a source of unwanted non-neuronal signal components, often called physiologic noise, in resting state (rs-) fMRI studies. Here, we use image-based retrospective correction of physiological motion (RETROICOR) with externally measured physiologic signals to investigate cardiac and respiratory hemodynamic phase functions reflected in rs-fMRI data. We find that the cardiac phase function is time shifted locally, while the respiratory phase function is described as single, fixed phase form across the brain. In light of these findings, we propose an update to Physiologic EStimation by Temporal ICA (PESTICA), our publically available software package that estimates physiologic signals when external physiologic measures are not available. This update incorporates: 1) auto-selection of slicewise physiologic regressors and generation of physiologic fixed phase regressors with total slices/TR sampling rate, 2) Fourier series expansion of the cardiac fixed phase regressor to account for time delayed cardiac noise 3) removal of cardiac and respiratory noise in imaging data. We compare the efficacy of the updated method to RETROICOR.

Leveraging redundancy in simultaneous multislice acquisitions to improve spike detection.

PURPOSE: To improve the performance of low-level spike noise artifact detection for daily quality assurance protocols by taking advantage of redundancy in simultaneous multislice (SMS) acquisitions. METHODS: Magnitude images were transformed into pseudo k-space images. Time series at each pseudo k-space point were detrended. A slice was determined to contain spiking artifact if it exceeded an intensity threshold and if all simultaneously acquired slices contained outliers. RESULTS: A total of 401 112 slices were inspected. Of these, 42 showed a spike artifact, based on visual inspection of image data and k-space data. With an intensity threshold of 4.6 SDs over time for each pseudo k-space point, all slices containing artifact were correctly flagged, and only 30 slices were incorrectly flagged when using the SMS criterion. Without the SMS criterion, 12 908 slices were incorrectly flagged as containing artifact. Without the SMS criterion, sensitivity to artifact would have to be sacrificed to substantially reduce the number of incorrectly flagged slices. CONCLUSION: This study demonstrates that the SMS criterion reduced the number of outliers reported to a manageable level while accurately identifying low-level spike artifacts. Successfully identifying low-level spikes allows early detection of hardware problems that can be fixed before the problem becomes debilitating and corrupts data. As part of a daily quality assurance protocol, the method prevents the need to retrospectively carry out time-intensive despiking and reanalysis of data.

Variable density magnetization transfer (vdMT) imaging for 7T MR imaging.

As the use of ultra-high field (UHF; ≥7T) magnetic resonance (MR) imaging expands, there is an increasing need to establish high-resolution MR imaging protocols for patients with neurological disease. Magnetization transfer (MT) imaging has been used to provide information about changes in the magnitude of the restricted protons that are caused by tissue damages. Several studies have found that MTR has a good sensitivity to measure changes in myelin concentration within the brain. Because of the much higher specific absorption rate (SAR) of tissue and longer acquisition time required for UHF, however, in-vivo studies using conventional pulsed MT sequences at UHF have not been well utilized. In this study, we introduce a new MT data acquisition approach using a 7T MR system, variable density magnetization transfer (vdMT) imaging, which can be reasonably included in a routine patient scan protocol with a much shorter scan time and reduced discomfort to the patient. To reduce SAR and scan time while maintaining at least similar MTR image quality to that obtained with the conventional method, a higher density of MT RF pulses was applied in the center of k-space, and sparsely applied MT RF pulses were used in the outer part of k-space. The fraction of k-space receiving 100% MT RF density and TR were optimized based on in-vivo ROI analysis, and results were confirmed with high-resolution MTR map using a vdMT approach from healthy controls and patients with multiple sclerosis (MS). The experimental results confirmed that vdMT imaging can cover a whole brain volume in an acceptable scan time for routine patient scans while providing MTR image quality at least similar to that obtained with conventional MT imaging (correlation coefficient=0.95 in an agar-gel phantom [MT offset frequency=1kH], 0.90 in a postmortem MS brain, and 0.85 in the 4 healthy volunteers). MS lesions were associated with signal reductions in the postmortem MS brains and in the patients with MS. In this study, we have described a new approach for acquiring high-resolution MTR map of the whole brain volume using 7T MR imaging. This vdMT method provides similar image quality to that obtained with the conventional method, and shortens the scan time by reducing SAR. These results suggest that vdMT approach is a method that could be used for UHF scans of patients with neurological disease.

Repeated head trauma is associated with smaller thalamic volumes and slower processing speed: the Professional Fighters' Brain Health Study.

OBJECTIVES: Cumulative head trauma may alter brain structure and function. We explored the relationship between exposure variables, cognition and MRI brain structural measures in a cohort of professional combatants. METHODS: 224 fighters (131 mixed martial arts fighters and 93 boxers) participating in the Professional Fighters Brain Health Study, a longitudinal cohort study of licensed professional combatants, were recruited, as were 22 controls. Each participant underwent computerised cognitive testing and volumetric brain MRI. Fighting history including years of fighting and fights per year was obtained from self-report and published records. Statistical analyses of the baseline evaluations were applied cross-sectionally to determine the relationship between fight exposure variables and volumes of the hippocampus, amygdala, thalamus, caudate, putamen. Moreover, the relationship between exposure and brain volumes with cognitive function was assessed. RESULTS: Increasing exposure to repetitive head trauma measured by number of professional fights, years of fighting, or a Fight Exposure Score (FES) was associated with lower brain volumes, particularly the thalamus and caudate. In addition, speed of processing decreased with decreased thalamic volumes and with increasing fight exposure. Higher scores on a FES used to reflect exposure to repetitive head trauma were associated with greater likelihood of having cognitive impairment. CONCLUSIONS: Greater exposure to repetitive head trauma is associated with lower brain volumes and lower processing speed in active professional fighters.

Fast magnetization transfer and apparent T1 imaging using a short saturation pulse with and without inversion preparation.

PURPOSE: Measurements of magnetization transfer (MT) metrics, such as the steady-state (SS) MT ratio and apparent longitudinal relaxation rate require multiple MT irradiation durations and a long experimental time. To overcome these problems, we propose a novel method using a short MT off-resonance pulse with and without on-resonance inversion preparation pulse. THEORY AND METHODS: Computer simulations were performed to examine the accuracy of the proposed method and to find the optimal off-resonance irradiation pulse duration (Tirad) and power level (ω1). Our approach, with echo planar imaging data acquisition, was applied to animals at 9.4 T and humans at 3 T with ω1/2π = 100 Hz and 177 Hz, respectively. Steady-state MT ratio and relaxation rate were obtained from a pair of MT images at a Tirad, with and without inversion. RESULTS: For Tirad ≥ 0.4 s, steady-state MT ratio, and relaxation rate measured at any single Tirad agreed well with those of the conventional fitting method that uses multiple Tirad. Our simulation indicates that a higher ω1 can use a shorter Tirad. CONCLUSION: Steady-state MT ratio and relaxation rate can be determined from MT data with only one, short Tirad by incorporation of an inversion prepulse. This MT imaging approach is simple, fast, and easily implementable.

Impulsiveness in professional fighters.

Sports involving repeated head trauma are associated with risk of neurodegenerative disorders such as chronic traumatic encephalopathy (CTE). Among the behavioral manifestations of CTE is increased impulsiveness. Here, the authors investigate the relationship between impulsiveness and exposure to head trauma in a large group of active professional fighters. Fighters tended to report less impulsiveness than did non-fighting control respondents. Overall, greater fight exposure was associated with higher levels of a specific form of impulsiveness, although there were differences between mixed martial arts fighters and boxers. Fight exposure was associated with reduction in volume of certain brain structures, and these changes were also associated with impulsiveness patterns. Longitudinal studies of professional fighters are important to understand the risk for neuropsychiatric problems.

Professional fighters brain health study: rationale and methods.

Repetitive head trauma is a risk factor for Alzheimer's disease and is the primary cause of chronic traumatic encephalopathy. However, little is known about the natural history of, and risk factors for, chronic traumatic encephalopathy or about means of early detection and intervention. The Professional Fighters Brain Health Study is a longitudinal study of active professional fighters (boxers and mixed martial artists), retired professional fighters, and controls matched for age and level of education. The main objective of the Professional Fighters Brain Health Study is to determine the relationships between measures of head trauma exposure and other potential modifiers and changes in brain imaging and neurological and behavioral function over time. The study is designed to extend over 5 years, and we anticipate enrollment of more than 400 boxers and mixed martial artists. Participants will undergo annual evaluations that include 3-tesla magnetic resonance imaging scanning, computerized cognitive assessments, speech analysis, surveys of mood and impulsivity, and blood sampling for genotyping and exploratory biomarker studies. Statistical models will be developed and validated to predict early and progressive changes in brain structure and function. A composite fight exposure index, developed as a summary measure of cumulative traumatic exposure, shows promise as a predictor of brain volumes and cognitive function.

Whole brain perfusion measurements using arterial spin labeling with multiband acquisition.

PURPOSE: The multiband (MB) excitation and reconstruction technique was both developed and evaluated for accelerated data acquisition of arterial spin labeling (ASL) to cover whole brain perfusion maps. THEORY AND METHODS: MB excitation was incorporated into a pulsed ASL (PASL) technique and compared with conventional single-band excitation PASL from healthy subjects, using a 32-channel head receiver coil at 3 T. The MB de-aliasing performance and effectiveness in perfusion measurement were measured with varying MB acceleration factors and gaps between MB excitations. RESULTS: The MB PASL perfusion maps were in good agreement with the conventional single-band PASL maps at matched slices. The imaging coverage could be effectively extended with the MB technique by a factor up to 5. A gap as small as 3 cm between MB excitations resulted in a comparable ASL signal loss and temporal-signal-to-noise ratio with single-band PASL. CONCLUSION: The MB ASL technique is an effective method to evaluate whole brain perfusion because it minimizes the temporal spread of labeled spins across slices, resulting in more accurate perfusion measurements.

Correction for arterial-tissue delay and dispersion in absolute quantitative cerebral perfusion DSC MR imaging.

The singular value decomposition deconvolution of cerebral tissue concentration-time curves with the arterial input function is commonly used in dynamic susceptibility contrast cerebral perfusion MR imaging. However, it is sensitive to the time discrepancy between the arrival of the bolus in the tissue concentration-time curve and the arterial input function signal. This normally causes inaccuracy in the quantitative perfusion maps due to delay and dispersion effects. A comprehensive correction algorithm has been achieved through slice-dependent time-shifting of the arterial input function, and a delay-dependent dispersion correction model. The correction algorithm was tested in 11 healthy subjects and three ischemic stroke patients scanned with a quantitative perfusion pulse sequence at 1.5 T. A validation study was performed on five patients with confirmed cerebrovascular occlusive disease scanned with MRI and positron emission tomography at 3.0 T. A significant effect (P < 0.05) was reported on the quantitative cerebral blood flow and mean transit time measurements (up to 50%). There was no statistically significant effect on the quantitative cerebral blood volume values. The in vivo results were in agreement with the simulation results, as well as previous literature. This minimizes the bias in patient diagnosis due to the existing errors and artifacts in dynamic susceptibility contrast imaging.

Automated brain tissue segmentation based on fractional signal mapping from inversion recovery Look-Locker acquisition.

Most current automated segmentation methods are performed on T(1)- or T(2)-weighted MR images, relying on relative image intensity that is dependent on other MR parameters and sensitive to B(1) magnetic field inhomogeneity. Here, we propose an image segmentation method based on quantitative longitudinal magnetization relaxation time (T(1)) of brain tissues. Considering the partial volume effect, fractional volume maps of brain tissues (white matter, gray matter, and cerebrospinal fluid) were obtained by fitting the observed signal in an inversion recovery procedure to a linear combination of three exponential functions, which represents the relaxations of each of the tissue types. A Look-Locker acquisition was employed to accelerate the acquisition process. The feasibility and efficacy of this proposed method were evaluated using simulations and experiments. The potential applications of this method in the study of neurological disease as well as normal brain development and aging are discussed.

Glioblastoma: a method for predicting response to antiangiogenic chemotherapy by using MR perfusion imaging--pilot study.

PURPOSE: To derive a magnetic resonance (MR)-based imaging metric that reflects local perfusion changes resulting from the administration of angiogenic-inhibiting chemotherapy in patients with recurrent glioblastoma multiforme (GBM). MATERIALS AND METHODS: In this retrospective Institutional Review Board-approved HIPAA-compliant study, 16 patients (12 men, four women; mean age, 51.8 years + or - 15.1 [standard deviation]) with recurrent GBM received bevacizumab every 3 weeks (15 mg per kilogram of body weight) as part of a clinical trial. Baseline MR images were acquired, and follow-up images were acquired every 6 weeks thereafter until tumor progression or death. Imaging included perfusion and T1-weighted contrast material-enhanced MR imaging. Perfusion images were analyzed both with and without correction for contrast material leakage. The volumes of interest were selected as enhancing voxels on T1-weighted contrast-enhanced MR images. Relative cerebral blood volume (rCBV) maps were created from analysis of MR perfusion images. The volumes of interest were used to calculate the following parameters: size, mean rCBV, mean leakage coefficient K(2), and hyperperfusion volume (HPV), which is the fraction of the tumor with an rCBV higher than a predetermined threshold. Percent change in each parameter from baseline to first follow-up was compared with time to progression (TTP) by using a Cox proportional hazards model with calculation of hazard ratios. RESULTS: The most significant hazard ratio was seen with a DeltaHPV cutoff of rCBV greater than 1.00 (hazard ratio, 1.077; 95% confidence interval: 1.026, 1.130; P = .002). The only significant ratios greater than one were those that resulted from perfusion calculated as mean rCBV and DeltaHPV. The ratios were also higher after correction for leakage. CONCLUSION: This pilot study derived an imaging metric (HPV) that reflects local perfusion changes in GBMs. This metric was found to show a significantly improved correlation to TTP as compared with more commonly used metrics.

Quantitative cerebral MR perfusion imaging: preliminary results in stroke.

PURPOSE: To evaluate quantitative cerebral blood flow (qCBF) with traditional time-based measurements or metrics of cerebral perfusion: time to peak (Tmax) and mean transit time (MTT) in stroke patients. MATERIALS AND METHODS: Nine ischemic stroke patients (four male, five female, 63 ± 16 years old) were included in the study which was Health Insurance Portability and Accountability Act compliant and institutional review board approved. Cerebral perfusion was quantified using the Bookend method. Mean values of qCBF, Tmax, and MTT were determined in regions of interest (ROIs). ROIs were drawn on diffusion weighted images in diffusion positive, critically ischemic (CI), in ipsilateral normal region immediately surrounding the critically ischemic region, the presumed penumbra (PP), and in contralateral diffusion negative control, presumed normal region (PN) of gray and white matter separately (GM and WM). RESULTS: In both GM and WM, qCBF measures distinguished the studied brain regions with the most markedly reduced values in regions corresponding to extent of likely ischemic injury. In planned comparisons, only qCBF measurements differed significantly between CI and PP tissues. ROC analysis supported the utility of qCBF for discriminating brain regions differing in the likely extent of ischemic injury (CI and PN regions - qCBF: area under the curve [AUC] = 0.96, Tmax: AUC = 0.96, MTT: AUC = 0.72). Importantly, qCBF afforded the best discrimination of CI and PP regions (qCBF: AUC = 0.82, Tmax: AUC = 0.65, MTT: AUC = 0.52). CONCLUSION: This initial evaluation indicates that quantitative MRI perfusion is feasible in ischemic stroke patients. qCBF derived with this strategy provide enhanced discrimination of CI and PP compared to time-based imaging metrics. This approach merits investigation in larger clinical studies.

Improved acceleration of phase-contrast flow imaging with magnitude difference regularization.

PURPOSE: To develop a regularized image reconstruction algorithm for improved scan acceleration of phase-contrast (PC) flow MRI. METHODS: Based on the magnitude similarity between bipolar-encoded k-space data, magnitude-difference regularization was incorporated into the conventional compressed sensing (CS) reconstruction. The gradient of the magnitude regularization was derived so the reconstruction problem can be solved using non-linear conjugate gradient with backtracking line search. Phase contrast flow data obtained in the peripheral arteries of healthy and patient subjects were retrospectively undersampled for testing the proposed reconstruction method. Three-dimensional velocity-encoded PC flow MRI was performed with prospective 4-fold undersampling for measuring arotic flow velocity in a healthy volunteer. RESULTS: In the femoral arteries of healthy volunteers, the root-mean-square (RMS) errors of mean velocities were 0.56 ± 0.09 cm/s with CS-only reconstruction and 0.46 ± 0.08 cm/s with addition of magnitude regularization for three-fold acceleration; 1.34 ± 0.17 cm/s (CS only) and 1.08 ± 0.15 cm/s (magnitude regularized) for four-fold acceleration. In the iliac arteries of the patient, the RMS errors of mean velocities were 0.72 ± 0.12 cm/s and 0.56 ± 0.10 for three-fold acceleration, and 1.75 ± 0.21 and 1.24 ± 0.19 cm/s for four-fold acceleration (in the order of CS-only and magnitude regularized reconstructions). In the popliteal arteries, the RMS errors were 0.61 ± 0.10 cm/s and 0.42 ± 0.11 for three-fold acceleration, and 1.41 ± 0.19 and 1.12 ± 0.17 cm/s for four-fold acceleration. The maximum through-plane mean flow velocities were measured as 63.2 cm/s and 84.5 cm/s in ascending and descending aortas, respectively. CONCLUSION: The addition of magnitude-difference regularization into conventional CS reconstruction improves the accuracy of image reconstruction using highly undersampled phase-contrast flow MR data.

Stability-Based Sparse Paradigm Free Mapping Algorithm for Deconvolution of Functional MRI Data.

Neuronal-related activity can be estimated from functional magnetic resonance imaging (fMRI) data with no knowledge of the timings of blood oxygenation level-dependent (BOLD) events by means of deconvolution with regularized least-squares. This work proposes two improvements on the deconvolution algorithm of sparse paradigm free mapping (SPFM): a new formulation that enables the estimation of neuronal events with long, sustained activity; and the implementation of a subsampling approach based on stability selection that avoids the choice of any regularization parameter. The proposed method is evaluated on real fMRI data and compared with both the original SPFM algorithm and conventional analysis with a general linear model (GLM) that is aware of the temporal model of the neuronal-related activity. We demonstrate that the novel stability-based SPFM algorithm yields activation maps with higher resemblance to the maps obtained with GLM analyses and offers improved detection of neuronal-related events over SPFM, particularly in scenarios with low contrast-to-noise ratio.

Fast high-resolution T1 mapping using inversion-recovery Look-Locker echo-planar imaging at steady state: optimization for accuracy and reliability.

A fast T(1) measurement sequence using inversion recovery Look-Locker echo-planar imaging at steady state (IR LL-EPI SS) is presented. Delay time for a full magnetization recovery is not required in the sequence, saving acquisition time significantly for high-resolution T(1) mapping. Imaging parameters of the IR LL-EPI SS sequence were optimized to minimize the bias from the excitation pulses imperfection and to maximize the accuracy and reliability of T(1) measurements, which are critical for its applications. Compared with the conventional inversion recovery Look-Locker echo-planar imaging (IR LL-EPI) sequence, IR LL-EPI SS method preserves similar accuracy and reliability, while saving 20% in acquisition time. Optimized IR LL-EPI SS provided quantitative T(1) mapping with 1 x 1 x 4 mm(3) resolution and whole-brain coverage (28 slices) in approximately 4 min.

Incidental magnetization transfer contrast by fat saturation preparation pulses in multislice Look-Locker echo planar imaging.

In this study, it is demonstrated that fat saturation (FS) preparation (prep) pulses generate incidental magnetization transfer contrast (MTC) in multislice Look-Locker (LL) imaging. It is shown that frequency-selective FS prep pulses can invoke MTC through the exchange between free and motion-restricted protons. Simulation reveals that the fractional signal loss by these MTC effects is more severe for smaller flip angles (FAs), shorter repetition times (TRs), and greater number of slices (SN). These incidental MTC effects result in a signal attenuation at a steady state (up to 30%) and a T(1) measurement bias (up to 20%) when using inversion recovery (IR) LL echo-planar imaging (EPI) sequences. Furthermore, it is shown that water-selective MRI using binomial pulses has the potential to minimize the signal attenuation and provide unbiased T(1) measurement without fat artifacts in MR images.

Quantification of cerebral perfusion using the "bookend technique": an evaluation in CNS tumors.

We present a method of quantifying cerebral blood volume using dynamic susceptibility contrast. Our approach combines T(2)-weighted echo planar imaging (EPI) pulse sequences and reference scans that determine the parenchymal T(1) changes resulting from an injection of a gadolinium chelate. This combined T(2)- and T(1)-weighted approach (the "bookend" technique) has been shown to be effective in the quantification of gradient-echo (GRE) (T(2)*-weighted) perfusion images but has not been applied to spin-echo EPI (SE-EPI) (T(2)-weighted) images. The physics related to blood volume measurement based on T(2)- and T(2)*-weighted EPI sequences is known to be different, and there is a question as to whether the bookend approach is effective with SE-EPI. We have compared the quantitative SE-EPI with GRE-EPI in a series of patients with central nervous system (CNS) tumors. We found that quantitative cerebral blood volume (qCBV) values for SE-EPI and GRE-EPI are in agreement with each other and with historical reference values. A subjective evaluation of image quality showed that image quality in the SE-EPI scans was high and exhibited high interreader agreement. We conclude that measuring qCBV using the bookend technique with SE-EPI images is possible and may be a viable alternative to GRE-EPI in the evaluation of CNS tumors.

CNR improvement of MP2RAGE from slice encoding directional acceleration.

PURPOSE: While MP2RAGE shows the potential to generate B1 insensitive T1 contrast, the long TR of MP2RAGE (≥6s at 7T) is essential to provide the large dynamic range of apparent T1 relaxation for dual inversion time acquisitions. We present a 2 direction (2D) accelerated MP2RAGE, which provides an increased flip angle while maintaining similar dynamic recovery as 1D accelerated MP2RAGE. METHOD: Simulations were conducted to optimize 2D accelerated MP2RAGE parameters and healthy subjects were scanned with 1D and 2D accelerated MP2RAGE at 7T. Images were compared visually and contrast to noise (CNR) between brain tissues was measured. RESULT: Simulations showed that CNR is primarly determined by the TR, followed by the number of the first partition encoding steps in MP2RAGE. Keeping TR constant, a smaller number of partition encoding steps increases the achievable maximal CNR. In-vivo 2D MP2RAGE improves CNR between white and gray matters by 9% when compared to 1D accelerated MP2RAGE with identical voxel size. CONCLUSION: We presented 2D accelated MP2RAGE at 7T with the increased flip angle. We show that this leads to CNR improvement, and consequently a reduction of scan time to be compared to 1D accelerated MP2RAGE.

The protective effect of education on cognition in professional fighters.

Education has a protective effect against cognitive deficits following various forms of brain insult. Professional fighting (boxing and mixed martial arts) provides a model for assessing the impact of cumulative brain injuries on cognition and brain health. In the current cross-sectional observational study, we explore whether education would be protective against cognitive loss in fighters. We tested 141 professional fighters using a computerized neurocognitive battery, in addition to structural MRI. We used automated segmentation software to compute the volumes of various brain structures. We found fighters with high school education or less to show more associations between fight exposure and cognitive test scores. The relationship between brain structure volume and exposure did not differ based on education. These results are interpreted as putatively showing a protective effect of education on functional integrity in fighters, although longitudinal data and a larger sample size are required to further understand this relationship.

Unbiased group-wise image registration: applications in brain fiber tract atlas construction and functional connectivity analysis.

We propose an unbiased implicit-reference group-wise (IRG) image registration method and demonstrate its applications in the construction of a brain white matter fiber tract atlas and the analysis of resting-state functional MRI (fMRI) connectivity. Most image registration techniques pair-wise align images to a selected reference image and group analyses are performed in the reference space, which may produce bias. The proposed method jointly estimates transformations, with an elastic deformation model, registering all images to an implicit reference corresponding to the group average. The unbiased registration is applied to build a fiber tract atlas by registering a group of diffusion tensor images. Compared to reference-based registration, the IRG registration improves the fiber track overlap within the group. After applying the method in the fMRI connectivity analysis, results suggest a general improvement in functional connectivity maps at a group level in terms of larger cluster size and higher average t-scores.