Cerebral blood flow is lower in youth with type 2 diabetes compared to obese controls: A pilot study.

AIM: The cerebral vasculature may be susceptible to the adverse effects of type 2 diabetes. In this pilot study, we compared cerebral blood flow (CBF) in youth with type 2 diabetes to obese, euglycemic controls, and explored the association between CBF and a non-invasive measure of atherosclerosis, carotid intima-medial thickness (IMT). METHODS: Global and regional CBF were compared between youth with type 2 diabetes (mean age 16.7 ± 2.0 years, n = 20) and age, race, and sex similar obese youth without diabetes (17.4 ± 1.9 years, n = 19) using arterial spin labeling magnetic resonance imaging. Mean CBF values were compared between groups. Voxel-wise results were evaluated for statistical significance (p < 0.05) after adjustment for multiple comparisons. Carotid IMT in the type 2 diabetes group was correlated with CBF. RESULTS: Compared to obese controls, the type 2 diabetes group had significantly lower global CBF (49.7 ± 7.2 vs. 63.8 ± 11.5 ml/gm/min, p < 0.001). Significantly lower CBF was observed in multiple brain regions for the type 2 diabetes group, while no regions with higher CBF were identified. In the type 2 diabetes group, carotid IMT was inversely correlated with CBF, both globally (r = -0.70, p = 0.002) and in regional clusters. CONCLUSIONS: In this pilot study, lower CBF was seen in youth with type 2 diabetes compared to youth with obesity and IMT was inversely correlated with CBF. Cerebrovascular impairment may be present in youth with type 2 diabetes. These findings could represent a mechanistic link to explain previously reported brain volume and neurocognitive differences.

New insight into the neural mechanisms of migraine in adolescents: Relationships with sleep.

OBJECTIVE: This case-control study examines if measures of subjective and objective (actigraphic) sleep difficulties mediate alterations in amygdalar connectivity in adolescents with migraine compared to healthy adolescents. BACKGROUND: Adolescents with migraine have different functional connectivity of the amygdala compared to individuals without migraine. Sleep is often disturbed in adolescents with migraine, and could contribute to the alterations in functional connectivity. METHODS: Twenty adolescents with migraine and 20 healthy controls were recruited from Cincinnati Children's Hospital. Participants completed surveys about their headaches and overall sleep quality, sleep hygiene, and perceived sleep difficulties (Insomnia Severity Scale [ISI]); completed wrist-worn actigraphy; and underwent a magnetic resonance imaging scan. RESULTS: Adolescents with migraine differed from healthy controls only in perceived difficulty in sleep initiation and maintenance (ISI: 8.5 ± 4.7 and 4.5 ± 3.7 [mean ± standard deviation], -4.00 [95% confidence: -6.7 to -1.3], p = 0.005) and had greater functional connectivity between the amygdala and the posterior cingulate cortex, precuneus, dorsolateral prefrontal, sensorimotor, and the occipital cortexes. The differences in functional connectivity of the amygdala were not mediated by the subjective/objective sleep measures (ISI/wake minutes after sleep onset). CONCLUSIONS: Adolescents with migraine have greater connectivity between the amygdala and areas involved in sensory, affective, and cognitive aspects of pain. These alterations may not be due to higher levels of sleep difficulties in adolescents with migraine, suggesting that both amygdala and sleep alterations may play an independent role in migraine pathophysiology. This advances the understanding of the mechanisms underlying pediatric migraine and can potentially advance migraine management.

Alterations in Brain Function After Cognitive Behavioral Therapy for Migraine in Children and Adolescents.

OBJECTIVES: This basic mechanistic study examined the changes in brain activation and resting-state connectivity after 8 weeks of CBT in youth with migraine. BACKGROUND: Cognitive behavioral therapy (CBT) is a psychological intervention that is effective in reducing pain in migraine patients. However, the neural mechanisms underlying CBT in adolescents with migraine are not yet known. METHODS: Eighteen adolescents with migraine (15 females, age 15.1 ± 2.1 years [mean ± SD]) completed 8 weekly CBT sessions. Before the first and after the final CBT session, participants underwent structural and resting-state blood-oxygen-level-dependent contrast MRI scans. Arterial spin labeling was also used to examine brain activation during the resting state. For connectivity analyses, the right and left amygdala were chosen as seed regions. Relationships of the time courses within these seeds with voxels across the whole brain were evaluated. RESULTS: Headache frequency decreased from 15 ± 7.4 headaches per month before CBT to 10 ± 7.4 after CBT (P < .001). After CBT, greater brain activations in frontal regions involved in cognitive regulation of pain were found. In addition, after CBT increased connectivity between the amygdala and frontal regions was observed. Associations between brain activation and amygdalar connectivity with a reduction in headache frequency were also observed. CONCLUSIONS: Alterations in brain function and amygdalar connectivity with areas involved in nociceptive processing, cognitive function, and emotional regulation may underlie the ability of CBT to aid in the prevention of headaches in migraine patients.

Obese adolescents with type 2 diabetes perform worse than controls on cognitive and behavioral assessments.

BACKGROUND: Children with type 1 diabetes demonstrate worse cognitive performance compared with their peers. Little is known regarding the cognitive and behavioral performance in obese adolescents with type 2 diabetes. METHODS: Cross sectional evaluation of 20 obese adolescents with type 2 diabetes and 20 healthy adolescents was performed in Cincinnati, Ohio. Cognitive tests that included measures of processing speed, working memory, verbal and semantic fluency and parent reports of executive function and problem behavior were compared. Academic achievement and the relationship between cognitive/behavioral scores and diabetes duration and diabetes control (hemoglobin A1c) were assessed in the type 2 diabetes group only. RESULTS: The type 2 diabetes group had mean duration of diabetes of 2.8 ± 2.2 yr and hemoglobin A1c of 7.9 ± 2.2%. Adolescents with type 2 diabetes scored lower than controls on tests of working and verbal memory and processing speed (all p < 0.05) and worse for Internalizing, Externalizing, and Total Problems behaviors on the Child Behavior Checklist (all p < 0.05). Adolescents with type 2 diabetes scored below the population mean in academic achievement, most notably calculation. Working memory and processing speed were negatively correlated with duration of diabetes (r = -0.50 and -0.47, respectively, p < 0.05). CONCLUSIONS: Obese youth with type 2 diabetes score poorly compared with controls on multiple assessments of cognitive function and adaptive behavior. Further work is needed to determine if these effects are driven by obesity, diabetes or other demographic and socioeconomic risk factors.

Rapid volumetric T1 mapping of the abdomen using three-dimensional through-time spiral GRAPPA.

PURPOSE: To develop an ultrafast T1 mapping method for high-resolution, volumetric T1 measurements in the abdomen. METHODS: The Look-Locker method was combined with a stack-of-spirals acquisition accelerated using three-dimensional (3D) through-time spiral GRAPPA reconstruction for fast data acquisition. A segmented k-space acquisition scheme was proposed and the time delay between segments for the recovery of longitudinal magnetization was optimized using Bloch equation simulations. The accuracy of this method was validated in a phantom experiment and in vivo T1 measurements were performed with 35 asymptomatic subjects on both 1.5 Tesla (T) and 3T MRI systems. RESULTS: Phantom experiments yielded close agreement between the proposed method and gold standard measurements for a large range of T1 values (200 to 1600 ms). The in vivo results further demonstrate that high-resolution T1 maps (2 × 2 × 4 mm(3)) for 32 slices can be achieved in a single clinically feasible breath-hold of approximately 20 s. The T1 values for multiple organs and tissues in the abdomen are in agreement with the published literature. CONCLUSION: A high-resolution 3D abdominal T1 mapping technique was developed, which allows fast and accurate T1 mapping of multiple abdominal organs and tissues in a single breath-hold.

Three-dimensional through-time radial GRAPPA for renal MR angiography.

PURPOSE: To achieve high temporal and spatial resolution for contrast-enhanced time-resolved MR angiography exams (trMRAs), fast imaging techniques such as non-Cartesian parallel imaging must be used. In this study, the three-dimensional (3D) through-time radial generalized autocalibrating partially parallel acquisition (GRAPPA) method is used to reconstruct highly accelerated stack-of-stars data for time-resolved renal MRAs. MATERIALS AND METHODS: Through-time radial GRAPPA has been recently introduced as a method for non-Cartesian GRAPPA weight calibration, and a similar concept can also be used in 3D acquisitions. By combining different sources of calibration information, acquisition time can be reduced. Here, different GRAPPA weight calibration schemes are explored in simulation, and the results are applied to reconstruct undersampled stack-of-stars data. RESULTS: Simulations demonstrate that an accurate and efficient approach to 3D calibration is to combine a small number of central partitions with as many temporal repetitions as exam time permits. These findings were used to reconstruct renal trMRA data with an in-plane acceleration factor as high as 12.6 with respect to the Nyquist sampling criterion, where the lowest root mean squared error value of 16.4% was achieved when using a calibration scheme with 8 partitions, 16 repetitions, and a 4 projection × 8 read point segment size. CONCLUSION: 3D through-time radial GRAPPA can be used to successfully reconstruct highly accelerated non-Cartesian data. By using in-plane radial undersampling, a trMRA can be acquired with a temporal footprint less than 4s/frame with a spatial resolution of approximately 1.5 mm × 1.5 mm × 3 mm.

Rapid time-resolved magnetic resonance angiography via a multiecho radial trajectory and GraDeS reconstruction.

Contrast-enhanced magnetic resonance angiography is challenging due to the need for both high spatial and temporal resolution. A multishot trajectory composed of pseudo-random rotations of a single multiecho radial readout was developed. The trajectory is designed to give incoherent aliasing artifacts and a relatively uniform distribution of projections over all time scales. A field map (computed from the same data set) is used to avoid signal dropout in regions of substantial field inhomogeneity. A compressed sensing reconstruction using the GraDeS algorithm was used. Whole brain angiograms were reconstructed at 1-mm isotropic resolution and a 1.1-s frame rate (corresponding to an acceleration factor > 100). The only parameter which must be chosen is the number of iterations of the GraDeS algorithm. A larger number of iterations improves the temporal behavior at cost of decreased image signal-to-noise ratio. The resulting images provide a good depiction of the cerebral vasculature and have excellent arterial/venous separation.

Time-efficient slab-selective water excitation for 3D MRI.

Spectral-Spatial (SPSP) radiofrequency pulses are simultaneously selective in both the spectral and spatial domains. To selectively excite water spins and exclude fat, the individual subpulses that make up a SPSP pulse must be short (<1 ms at 4 T). A short subpulse duration limits the sharpness of the spatial slabs that can be excited when using a traditional SPSP pulse design approach. In this manuscript, the authors present an algorithm for designing SPSP pulses with substantially reduced maximum B(1) amplitudes and specific absorption rates. The proposed algorithm alternates between iterative design of the radiofrequency waveform for a given gradient shape and minimum-time variable-rate selective excitation reshaping of the gradient waveform. This approach is shown to reduce peak B(1) amplitudes in iteratively designed SPSP pulses by an order of magnitude. Unlike the use of regularization to control peak B(1) or specific absorption rate, the proposed method does not comprise the quality of the excitation profile. To achieve high-quality profiles, it was necessary to design the radiofrequency pulses for a measured rather than ideal gradient waveform. Slab-selective water excitation pulses with durations of 4.1 and 9.2 ms (fractional transition widths of 0.14 and 0.073, respectively) are demonstrated at 4 T.

Amygdalar functional connectivity during resting and evoked pain in youth with functional abdominal pain disorders.

ABSTRACT: Pediatric functional abdominal pain disorders (FAPD) are highly prevalent, difficult to diagnose, and challenging to treat. The brain systems supporting FAPD remain poorly understood. This investigation examined the neuromechanisms of FAPD during a well-tolerated visceral pain induction task, the water load symptom provocation task (WL-SPT). Youth between the ages of 11 and 17 years participated. Functional connectivity (FC) was examined through the blood oxygenation level-dependent effect using the left and right amygdala (AMY) as seed regions. Relationships of the time courses within these seeds with voxels across the whole brain were evaluated. Arterial spin labeling was used to assess regional brain activation by examining cerebral blood flow. Increased FC between the left AMY with regions associated with nociceptive processing (eg, thalamus) and right AMY FC changes with areas associated with cognitive functioning (dorsolateral prefrontal cortex) and the default mode network (DMN; parietal lobe) were observed in youth with FAPD after the WL-SPT. These changes were related to changes in pain unpleasantness. Amygdala FC changes post-WL-SPT were also related to changes in pain intensity. Amygdala FC with the DMN in youth with FAPD also differed from healthy controls. Global cerebral blood flow changes were also noted between FAPD and healthy controls, but no significant differences in grey matter were detected either between groups or during the WL-SPT in youth with FAPD. Findings confirm youth with FAPD undergo changes in brain systems that could support the development of biomarkers to enhance understanding of the mechanisms of pain and treatment response.

Identification of neural and psychophysical predictors of headache reduction after cognitive behavioral therapy in adolescents with migraine.

ABSTRACT: Cognitive behavioral therapy (CBT) is a psychological intervention that involves development of coping strategies to reduce the experience of pain. Although CBT is a promising intervention to reduce headache days in patients with migraine, it may not be effective for all patients. Thus, there is a need to identify markers that could predict which patients will respond to CBT. We aimed to determine whether baseline brain function and amygdalar connectivity, assessed by functional magnetic resonance imaging, or pain modulation capacities, assessed by the conditioned pain modulation (CPM) response, can predict a reduction in headache days after CBT in adolescents with migraine. Patients with migraine (n = 20; age range 10-17 years) completed 8 weekly CBT sessions. The CPM response was examined in the trapezius and the leg. Headache days significantly decreased after CBT (P < 0.001). Greater functional connectivity before CBT between the right amygdala and frontal gyrus, anterior cingulate cortex, and precentral gyrus was related to greater headache reduction after CBT. Greater reduction in headache days after CBT was related with less efficient CPM response before CBT at the trapezius (r = -0.492, P = 0.028) but not at the leg. This study found that headache reduction after CBT was related to right amygdala connectivity with frontal and sensorimotor regions at baseline as well as baseline pain modulation capacities. These findings suggest that individual differences in brain function and pain modulation can be associated with clinical improvements and help with determination of CBT responsiveness.

Rapid 3D radial multi-echo functional magnetic resonance imaging.

Functional magnetic resonance imaging with readouts at multiple echo times is useful for optimizing sensitivity across a range of tissue T2* values as well as for quantifying T2*. With single-shot acquisitions, both the minimum TE value and the number of TEs which it is possible to collect within a single TR are limited by the long echo-planar imaging readout duration (20-40 ms). In the present work, a multi-shot 3D radial acquisition which allows rapid whole-brain imaging at a range of echo times is proposed. The proposed 3D k-space coverage is implemented via a series of rotations of a single 2D interleaf. Data can be reconstructed at a variety of temporal resolutions from a single dataset, allowing for a flexible tradeoff between temporal resolution and BOLD contrast to noise ratio. It is demonstrated that whole-brain images at 5 echo times (TEs from 10 to 46 ms) can be acquired at a temporal rate as rapid as 400 ms/volume (3.75 mm isotropic resolution). Activation maps for a simultaneous motor/visual task consistent across multiple acceleration factors are obtained. Weighted combination of the echoes results in Z-scores that are significantly (p=0.016) higher than those resulting from any of the individual echo time images.

Single-shot turbo spin echo acquisition for in vivo cardiac diffusion MRI.

Diffusion MRI offers the ability to noninvasively characterize the microstructure of myocardium tissue and detect disease related pathology in cardiovascular examination. This study investigates the feasibility of in vivo cardiac diffusion MRI under free-breathing condition. A high-speed imaging technique, correlation imaging, is used to enable single-shot turbo spin echo for free-breathing cardiac data acquisition. The obtained in vivo cardiac diffusion-weighted images illustrate robust image quality and minor geometry distortions. The resultant diffusion scalar maps show reliable quantitative values consistent with those previously published in the literature. It is demonstrated that this technique has the potential for in vivo free-breathing cardiac diffusion MRI.

Free-breathing liver perfusion imaging using 3-dimensional through-time spiral generalized autocalibrating partially parallel acquisition acceleration.

OBJECTIVES: The goal of this study was to develop free-breathing high-spatiotemporal resolution dynamic contrast-enhanced liver magnetic resonance imaging using non-Cartesian parallel imaging acceleration, and quantitative liver perfusion mapping. MATERIALS AND METHODS: This study was approved by the local institutional review board and written informed consent was obtained from all participants. Ten healthy subjects and 5 patients were scanned on a Siemens 3-T Skyra scanner. A stack-of-spirals trajectory was undersampled in-plane with a reduction factor of 6 and reconstructed using 3-dimensional (3D) through-time non-Cartesian generalized autocalibrating partially parallel acquisition. High-resolution 3D images were acquired with a true temporal resolution of 1.6 to 1.9 seconds while the subjects were breathing freely. A dual-input single-compartment model was used to retrieve liver perfusion parameters from dynamic contrast-enhanced magnetic resonance imaging data, which were coregistered using an algorithm designed to reduce the effects of dynamic contrast changes on registration. Image quality evaluation was performed on spiral images and conventional images from 5 healthy subjects. RESULTS: Images with a spatial resolution of 1.9 × 1.9 × 3 mm3 were obtained with whole-liver coverage. With an imaging speed of better than 2 s/vol, free-breathing scans were achieved and dynamic changes in enhancement were captured. The overall image quality of free-breathing spiral images was slightly lower than that of conventional long breath-hold Cartesian images, but it provided clinically acceptable or better image quality. The free-breathing 3D images were registered with almost no residual motion in liver tissue. After the registration, quantitative whole-liver 3D perfusion maps were obtained and the perfusion parameters are all in good agreement with the literature. CONCLUSIONS: This high-spatiotemporal resolution free-breathing 3D liver imaging technique allows voxelwise quantification of liver perfusion.

Functional imaging with Turbo-CASL: transit time and multislice imaging considerations.

The optimal use of turbo continuous arterial spin labeling (Turbo-CASL) for functional imaging in the presence of activation-induced transit time (TT) changes was investigated. Functional imaging of a bilateral finger-tapping task showed improved sensitivity for Turbo-CASL as compared to traditional CASL techniques for four of six subjects when scanned at an appropriate repetition time (TR). Both experimental and simulation results suggest that for optimal functional sensitivity with Turbo-CASL, the pulse TR should be set to a value that is 100-200 ms less than the resting-state TT. Simulations were also run to demonstrate the differences in TT sensitivity of different slices within a multislice acquisition, and the signal loss that is expected as the number of slices is increased. Despite the lower baseline ASL signal provided by the Turbo-CASL acquisition, one can achieve equal or improved functional sensitivity due in part to the signal enhancement that accompanies the decrease in TT upon activation. Turbo-CASL is thus a promising technique for functional ASL at higher temporal resolution.

Estimation efficiency and statistical power in arterial spin labeling fMRI.

Arterial spin labeling (ASL) data are typically differenced, sometimes after interpolation, as part of preprocessing before statistical analysis in fMRI. While this process can reduce the number of time points by half, it simplifies the subsequent signal and noise models (i.e., smoothed box-car predictors and white noise). In this paper, we argue that ASL data are best viewed in the same data analytic framework as BOLD fMRI data, in that all scans are modeled and colored noise is accommodated. The data are not differenced, but the control/label effect is implicitly built into the model. While the models using differenced data may seem easier to implement, we show that differencing models fit with ordinary least squares either produce biased estimates of the standard errors or suffer from a loss in efficiency. The main disadvantage to our approach is that non-white noise must be modeled in order to yield accurate standard errors, however, this is a standard problem that has been solved for BOLD data, and the very same software can be used to account for such autocorrelated noise.

Application of selective saturation to image the dynamics of arterial blood flow during brain activation using magnetic resonance imaging.

A saturation-based approach is proposed to image the arterial blood flow signal with temporal resolution of 1 to 2 s and in-plane spatial resolution of a few millimeters. Using a saturation approach to suppress the undesired background stationary signal allows the blood water that enters the slice to be imaged at some specified later time. Since the blood protons that are being imaged are not restricted to the intravascular space, this technique is also sensitive to tissue perfusion signal contributions. The signal uptake characteristics of the saturation method proposed were used to study the different signal contributions as a function of the acquisition parameters. A typical perfusion acquisition (FAIR) was also used for comparison. The proposed method was demonstrated in a functional motor activation experiment and the observed signal changes were smaller than those obtained using the FAIR acquisition. The dynamics of the saturation method and FAIR temporal signal changes were investigated and time constants between 2 and 44 s were estimated. The tissue signal contribution to the saturation method's signal was small over the range of acquisition parameters that sensitized it to the arterial compartment.

Vascular dynamics and BOLD fMRI: CBF level effects and analysis considerations.

Changes in the cerebral blood flow (CBF) baseline produce significant changes to the hemodynamic response. This work shows that increases in the baseline blood flow level produce blood oxygenation-level dependent (BOLD) and blood flow responses that are slower and lower in amplitude, while decreases in the baseline blood flow level produce faster and higher amplitude hemodynamic responses. This effect was characterized using a vascular model of the hemodynamic response that separated arterial blood flow response from the venous blood volume response and linked the input stimulus to the vascular response. The model predicted the baseline blood flow level effects to be dominated by changes in the arterial vasculature. Specifically, it predicted changes in the arterial blood flow time constant and venous blood volume time constant parameters of +294% and -24%, respectively, for a 27% increase in the baseline blood flow. The vascular model performance was compared to an empirical model of the hemodynamic response. The vascular and empirical hemodynamic models captured most of the baseline blood flow level effects observed and can be used to correct for these effects in fMRI data. While the empirical hemodynamic model is easy to implement, it did not incorporate any explicit physiological information.

Quantification of perfusion fMRI using a numerical model of arterial spin labeling that accounts for dynamic transit time effects.

A new approach to modeling the signal observed in arterial spin labeling (ASL) experiments during changing perfusion conditions is presented in this article. The new model uses numerical methods to extend first-order kinetic principles to include the changes in arrival time of the arterial tag that occur during neuronal activation. Estimation of the perfusion function from the ASL signal using this model is also demonstrated. The estimation algorithm uses a roughness penalty as well as prior information. The approach is demonstrated in numerical simulations and human experiments. The approach presented here is particularly suitable for fast ASL acquisition schemes, such as turbo continuous ASL (Turbo-CASL), which allows subtraction pairs to be acquired in less than 3 s but is sensitive to arrival time changes. This modeling approach can also be extended to other acquisition schemes.

Fast, pseudo-continuous arterial spin labeling for functional imaging using a two-coil system.

A fast, two-coil, pseudo-continuous labeling scheme is presented. This new scheme permits the collection of a multislice subtraction pair in <3 s, depending on the subject's arterial transit times. The method consists of acquiring both control and tag images immediately after a labeling period that matches the arterial transit time. The theoretical basis of the technique, and simulations of the signal during changes in both transit time and perfusion are presented. Experimental data from functional imaging experiments were collected to demonstrate the technique and its characteristics.