Language Exposure and Brain Myelination in Early Development.

The language environment to which children are exposed has an impact on later language abilities as well as on brain development; however, it is unclear how early such impacts emerge. This study investigates the effects of children's early language environment and socioeconomic status (SES) on brain structure in infancy at 6 and 30 months of age (both sexes included). We used magnetic resonance imaging to quantify concentrations of myelin in specific fiber tracts in the brain. Our central question was whether Language Environment Analysis (LENA) measures from in-home recording devices and SES measures of maternal education predicted myelin concentrations over the course of development. Results indicate that 30-month-old children exposed to larger amounts of in-home adult input showed more myelination in the white matter tracts most associated with language. Right hemisphere regions also show an association with SES, with older children from more highly educated mothers and exposed to more adult input, showing greater myelin concentrations in language-related areas. We discuss these results in relation to the current literature and implications for future research.SIGNIFICANCE STATEMENT This is the first study to look at how brain myelination is impacted by language input and socioeconomic status early in development. We find robust relationships of both factors in language-related brain areas at 30 months of age.

Naturalistic Bladder Filling Reveals Subtypes in Overactive Bladder Syndrome That Differentially Engages Urinary Urgency-Related Brain Circuits: Results From the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN).

PURPOSE: Overactive bladder (OAB) may be attributed to dysfunction in supraspinal brain circuits. Overactive bladder participants enrolled in the LURN (Symptoms of Lower Urinary Tract Dysfunction Research Network) study reported sensations of urinary urgency during a bladder-filling paradigm while undergoing brain functional MRI to map supraspinal dysfunction. MATERIALS AND METHODS: OAB participants and controls (CONs) completed 2 resting-state functional MRI scans following consumption of 350 mL water. Scans were conducted at fuller and emptier bladder states, interleaved with voiding. Urgency ratings (0-10) were assessed. Patterns of urgency during bladder filling were investigated using latent class trajectory models. Clusters of participants encompassing each pattern (ie, subtype) were derived from aggregated groups of OAB and CON independent of diagnosis. RESULTS: Two distinct patterns of urgency trajectories were revealed: first subtype with OAB and CON who were unresponsive to bladder filling (OAB-1 and CON-1) and second highly responsive subtype predominantly containing OAB (OAB-2). OAB-2 participants scored significantly higher on urinary symptoms but not pain or psychosocial measures. Neuroimaging analyses showed change in urgency due to both bladder filling and voided volume related to multiple loci of brain network connectivity in OAB-2, and in some cases, different than OAB-1 and/or CON-1. Sensorimotor to dorsomedial/dorsolateral prefrontal connectivity mediated the relationship between stimulus (voided volume) and percept (urgency) in OAB-2. CONCLUSIONS: Our results reveal different OAB subtypes with latent class trajectory models of urgency ratings during natural bladder filling. Functional MRI revealed differences in pathophysiology between subtypes, namely sensorimotor-prefrontal connectivity is a key locus in OAB patients with higher urinary symptoms.

Structural Changes in Brain White Matter Tracts Associated With Overactive Bladder Revealed by Diffusion Tensor Magnetic Resonance Imaging: Findings From a Symptoms of Lower Urinary Tract Dysfunction Research Network Cross-Sectional Case-Control Study.

PURPOSE: Our objective was to investigate structural changes in brain white matter tracts using diffusion tensor imaging (DTI) in patients with overactive bladder (OAB). MATERIALS AND METHODS: Treatment-seeking OAB patients and matched controls enrolled in the cross-sectional case-control LURN (Symptoms of Lower Urinary Tract Dysfunction Research Network) Neuroimaging Study received a brain DTI scan. Microstructural integrity of brain white matter was assessed using fractional anisotropy (FA) and mean diffusivity. OAB and urgency urinary incontinence (UUI) symptoms were assessed using the OAB Questionnaire Short-Form and International Consultation on Incontinence Questionnaire-Urinary Incontinence. The Lower Urinary Tract Symptoms Tool UUI questions and responses were correlated with FA values. RESULTS: Among 221 participants with evaluable DTI data, 146 had OAB (66 urinary urgency-only without UUI, 80 with UUI); 75 were controls. Compared with controls, participants with OAB showed decreased FA and increased mean diffusivity, representing greater microstructural abnormalities of brain white matter tracts among OAB participants. These abnormalities occurred in the corpus callosum, bilateral anterior thalamic radiation and superior longitudinal fasciculus tracts, and bilateral insula and parahippocampal region. Among participants with OAB, higher OAB Questionnaire Short-Form scores were associated with decreased FA in the left inferior fronto-occipital fasciculus, P < .0001. DTI differences between OAB and controls were driven by the urinary urgency-only (OAB-dry) but not the UUI (OAB-wet) subgroup. CONCLUSIONS: Abnormalities in microstructural integrity in specific brain white matter tracts were more frequent in OAB patients. More severe OAB symptoms were correlated with greater degree of microstructural abnormalities in brain white matter tracts in patients with OAB. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02485808.

Longitudinal Clinical and Biological Characteristics in Juvenile-Onset Huntington's Disease.

BACKGROUND: Juvenile-onset Huntington's disease (JOHD) is a rare form of Huntington's disease (HD) characterized by symptom onset before the age of 21 years. Observational data in this cohort is lacking. OBJECTIVES: Quantify measures of disease progression for use in clinical trials of patients with JOHD. METHODS: Participants who received a motor diagnosis of HD before the age of 21 were included in the Kids-JOHD study. The comparator group consisted of children and young adults who were at-risk for inheriting the genetic mutation that causes HD, but who were found to have a CAG repeat in the non-expanded range (gene non-expanded [GNE]). RESULTS: Data were obtained between March 17, 2006, and February 13, 2020. There were 26 JOHD participants and 78 GNE participants who were comparable on age (16.03 vs. 14.43, respectively) and sex (53.8% female vs. 57.7% female, respectively). The mean annualized decrease in striatal volume in the JOHD group was -3.99% compared to -0.06% in the GNE (mean difference [MD], -3.93%; 95% confidence intervals [CI], [-4.98 to -2.80], FDR < 0.0001). The mean increase in the Unified Huntington's Disease Rating Scale Total Motor Score per year in the JOHD group was 7.29 points compared to a mean decrease of -0.21 point in the GNE (MD, 7.5; 95% CI, [5.71-9.28], FDR < 0·0001). CONCLUSIONS: These findings demonstrate that structural brain imaging and clinical measures in JOHD may be potential biomarkers of disease progression for use in clinical trials. Collaborative efforts are required to validate these results in a larger cohort of patients with JOHD. © 2022 International Parkinson and Movement Disorder Society.

Posterior Fossa Sub-Arachnoid Cysts Observed in Patients with Bipolar Disorder: a Retrospective Cohort Study.

Posterior fossa arachnoid cysts (PFACs) are rare congenital abnormalities observed in 0.3 to 1.7% of the population and are traditionally thought to be benign. While conducting a neuroimaging study investigating cerebellar structure in bipolar disorder, we observed a higher incidence of PFACs in bipolar patients (5 of 75; 6.6%) compared to the neuronormative control group (1 of 54; 1.8%). In this report, we detail the cases of the five patients with bipolar disorder who presented with PFACs. Additionally, we compare neuropsychiatric measures and cerebellar volumes of these patients to neuronormative controls and bipolar controls (those with bipolar disorder without neuroanatomical abnormalities). Our findings suggest that patients with bipolar disorder who also present with PFACs may have a milder symptom constellation relative to patients with bipolar disorder and no neuroanatomical abnormalities. Furthermore, our observations align with prior literature suggesting an association between PFACs and psychiatric symptoms that warrants further study. While acknowledging sample size limitations, our primary aim in the present work is to highlight a connection between PFACs and BD-associated symptoms and encourage further study of cerebellar abnormalities in psychiatry.

Circadian timing, melatonin and hippocampal volume in later-life adults.

Hippocampal atrophy is a prominent neurodegenerative feature of Alzheimer's disease and related dementias. Alterations in circadian rhythms can exacerbate cognitive aging and neurodegeneration. This study aimed to examine how dim light melatonin onset and melatonin levels are associated with hippocampal volume in cognitively healthy individuals. We studied data from 52 later-life adults (mean age ± SD = 70.0 ± 6.3 years). T1-weighted anatomical images from 3.0 T magnetic resonance imaging data were collected and processed using the BRAINSTools toolbox. Dim light melatonin onset was used to assess circadian timing. The area under the curve was calculated to quantify melatonin concentration levels 6 hr before bedtime, and 14-day wrist actigraphy data were used to assess habitual bedtime. Multiple linear regression modelling with hippocampal volume as the dependent variable was used to analyse the data adjusting for age and sex. The average dim light melatonin onset was 19:45 hours (SD = 84 min), and area under the curve of melatonin levels 6 hr before habitual bedtime was 38.4 pg ml-1 × hr (SD = 29.3). We found that later dim light melatonin onset time (b = 0.16, p = 0.005) and greater area under the curve of melatonin levels 6 hr before habitual bedtime (b = 0.05, p = 0.046) were associated with greater adjusted hippocampal volume. The time between dim light melatonin onset and the midpoint of sleep timing was not associated with hippocampal volume. The findings suggest that earlier circadian timing (dim light melatonin onset) and reduced melatonin may be associated with reduced hippocampal volume in older adults. Future research will help researchers utilize circadian rhythm information to delay brain aging.

Multi-band- and in-plane-accelerated diffusion MRI enabled by model-based deep learning in q-space and its extension to learning in the spherical harmonic domain.

PURPOSE: To propose a new method for the recovery of combined in-plane- and multi-band (MB)-accelerated diffusion MRI data. METHODS: Combining MB acceleration with in-plane acceleration is crucial to improve the time efficiency of high (angular and spatial) resolution diffusion scans. However, as the MB factor and in-plane acceleration increase, the reconstruction becomes challenging due to the heavy aliasing. The new reconstruction utilizes an additional q-space prior to constrain the recovery, which is derived from the previously proposed qModeL framework. Specifically, the qModeL prior provides a pre-learned representation of the diffusion signal space to which the measured data belongs. We show that the pre-learned q-space prior along with a model-based iterative reconstruction that accommodate multi-band unaliasing, can efficiently reconstruct the in-plane- and MB-accelerated data. The power of joint reconstruction is maximally utilized by using an incoherent under-sampling pattern in the k-q domain. We tested the proposed method on single- and multi-shell data, with high/low angular resolution, high/low spatial resolution, healthy/abnormal tissues, and 3T/7T field strengths. Furthermore, the learning is extended to the spherical harmonic basis, to provide a rotational invariant learning framework. RESULTS: The qModeL joint reconstruction is shown to simultaneously unalias and jointly recover DWIs with reasonable accuracy in all the cases studied. The reconstruction error from 18-fold accelerated multi-shell datasets was <3%. The microstructural maps derived from the accelerated acquisitions also exhibit reasonable accuracy for both healthy and abnormal tissues. The deep learning (DL)-enabled reconstructions are comparable to those derived using traditional methods. CONCLUSION: qModeL enables the joint recovery of combined in-plane- and MB-accelerated dMRI utilizing DL.

Altered white matter microstructural organization in posttraumatic stress disorder across 3047 adults: results from the PGC-ENIGMA PTSD consortium.

A growing number of studies have examined alterations in white matter organization in people with posttraumatic stress disorder (PTSD) using diffusion MRI (dMRI), but the results have been mixed which may be partially due to relatively small sample sizes among studies. Altered structural connectivity may be both a neurobiological vulnerability for, and a result of, PTSD. In an effort to find reliable effects, we present a multi-cohort analysis of dMRI metrics across 3047 individuals from 28 cohorts currently participating in the PGC-ENIGMA PTSD working group (a joint partnership between the Psychiatric Genomics Consortium and the Enhancing NeuroImaging Genetics through Meta-Analysis consortium). Comparing regional white matter metrics across the full brain in 1426 individuals with PTSD and 1621 controls (2174 males/873 females) between ages 18-83, 92% of whom were trauma-exposed, we report associations between PTSD and disrupted white matter organization measured by lower fractional anisotropy (FA) in the tapetum region of the corpus callosum (Cohen's d = -0.11, p = 0.0055). The tapetum connects the left and right hippocampus, for which structure and function have been consistently implicated in PTSD. Results were consistent even after accounting for the effects of multiple potentially confounding variables: childhood trauma exposure, comorbid depression, history of traumatic brain injury, current alcohol abuse or dependence, and current use of psychotropic medications. Our results show that PTSD may be associated with alterations in the broader hippocampal network.

Probing the Neural Systems Underlying Flexible Dimensional Attention.

Flexibly shifting attention between stimulus dimensions (e.g., shape and color) is a central component of regulating cognition for goal-based behavior. In the present report, we examine the functional roles of different cortical regions by manipulating two demands on task switching that have been confounded in previous studies-shifting attention between visual dimensions and resolving conflict between stimulus-response representations. Dimensional shifting was manipulated by having participants shift attention between dimensions (either shape or color; dimension shift) or keeping the task-relevant dimension the same (dimension same). Conflict between stimulus-response representations was manipulated by creating conflict between response-driven associations from the previous set of trials and the stimulus-response mappings on the current set of trials (e.g., making a leftward response to a red stimulus during the previous task, but being required to make a rightward response to a red stimulus in the current task; stimulus-response conflict), or eliminating conflict by altering the features of the dimension relevant to the sorting rule (stimulus-response no-conflict). These manipulations revealed activation along a network of frontal, temporal, parietal, and occipital cortices. Specifically, dimensional shifting selectively activated frontal and parietal regions. Stimulus-response conflict, on the other hand, produced decreased activation in temporal and occipital cortices. Occipital regions demonstrated a complex pattern of activation that was sensitive to both stimulus-response conflict and dimensional attention switching. These results provide novel information regarding the distinct role that frontal cortex plays in shifting dimensional attention and posterior cortices play in resolving conflict at the stimulus level.

Hippocampal acidity and volume are differentially associated with spatial navigation in older adults.

The hippocampus is negatively affected by aging and is critical for spatial navigation. While there is evidence that wayfinding navigation tasks are especially sensitive to preclinical hippocampal deterioration, these studies have primarily used volumetric hippocampal imaging without considering microstructural properties or anatomical variation within the hippocampus. T1ρ is an MRI measure sensitive to regional pH, with longer relaxation rates reflecting acidosis as a marker of metabolic dysfunction and neuropathological burden. For the first time, we investigate how measures of wayfinding including landmark location learning and delayed memory in cognitively normal older adults (N = 84) relate to both hippocampal volume and T1ρ in the anterior and posterior hippocampus. Regression analyses revealed hippocampal volume was bilaterally related to learning, while right lateralized T1ρ was related to delayed landmark location memory and bilateral T1ρ was related to the delayed use of a cognitive map. Overall, results suggest hippocampal volume and T1ρ relaxation rate tap into distinct mechanisms involved in preclinical cognitive decline as assessed by wayfinding navigation, and laterality influenced these relationships more than the anterior-posterior longitudinal axis of the hippocampus.

qModeL: A plug-and-play model-based reconstruction for highly accelerated multi-shot diffusion MRI using learned priors.

PURPOSE: To introduce a joint reconstruction method for highly undersampled multi-shot diffusion weighted (msDW) scans. METHODS: Multi-shot EPI methods enable higher spatial resolution for diffusion MRI, but at the expense of long scan-time. Highly accelerated msDW scans are needed to enable their utilization in advanced microstructure studies, which require high q-space coverage. Previously, joint k-q undersampling methods coupled with compressed sensing were shown to enable very high acceleration factors. However, the reconstruction of this data using sparsity priors is challenging and is not suited for multi-shell data. We propose a new reconstruction that recovers images from the combined k-q data jointly. The proposed qModeL reconstruction brings together the advantages of model-based iterative reconstruction and machine learning, extending the idea of plug-and-play algorithms. Specifically, qModeL works by prelearning the signal manifold corresponding to the diffusion measurement space using deep learning. The prelearned manifold prior is incorporated into a model-based reconstruction to provide a voxel-wise regularization along the q-dimension during the joint recovery. Notably, the learning does not require in vivo training data and is derived exclusively from biophysical modeling. Additionally, a plug-and-play total variation denoising provides regularization along the spatial dimension. The proposed framework is tested on k-q undersampled single-shell and multi-shell msDW acquisition at various acceleration factors. RESULTS: The qModeL joint reconstruction is shown to recover DWIs from 8-fold accelerated msDW acquisitions with error less than 5% for both single-shell and multi-shell data. Advanced microstructural analysis performed using the undersampled reconstruction also report reasonable accuracy. CONCLUSION: qModeL enables the joint recovery of highly accelerated multi-shot dMRI utilizing learning-based priors. The bio-physically driven approach enables the use of accelerated multi-shot imaging for multi-shell sampling and advanced microstructure studies.

Preliminary evaluation of pre-speech and neurodevelopmental measures in 7-11-week-old infants with isolated oral clefts.

BACKGROUND: The purpose of this research study was to evaluate the earliest markers of vocal functioning and neurological development in infants with isolated oral cleft of the lip and/or palate (iCL/P). METHODS: Participants were recruited through advertisements and clinic visits at a local mid-western university. A total of eight participants (four unaffected and four with iCL/P), ranging in age from 7.29 to 11.57 weeks, were enrolled and completed demographic and pre-speech measures. A subset of six males (four unaffected and two with iCL/P) successfully completed a structural magnetic resonance imaging scan. RESULTS: Patterns of disrupted vocal control and reduced myelinated white matter were found in participants with iCL/P. CONCLUSIONS: The findings of this study provide a foundation from which to build further research on the neuronal development of infants with oral clefts: the need to evaluate measures of cortical development, inclusion of information on anesthesia exposure and airway obstruction, and suggestions for avoiding identified pitfalls/blocks to obtaining data are discussed. IMPACT: Research in children with isolated oral clefts has demonstrated higher rates of learning disorders connected to subtle differences in brain structure. There is no work evaluating the potential impact of exposure to anesthesia on development. This is the first known attempt to evaluate brain structure and function in infants with isolated oral clefts before exposure to anesthesia. Potential trends of early vocal issues and structural brain differences (less myelinated white matter) were identified in infants with isolated oral clefts compared to unaffected controls. Differences in brain structure and function in infants with isolated oral clefts may be present before surgery.

The functional brain networks that underlie visual working memory in the first two years of life.

Visual working memory (VWM) is a central cognitive system used to compare views of the world and detect changes in the local environment. This system undergoes dramatic development in the first two years; however, we know relatively little about the functional organization of VWM at the level of the brain. Here, we used image-based functional near-infrared spectroscopy (fNIRS) to test four hypotheses about the spatial organization of the VWM network in early development. Four-month-olds, 1-year-olds, and 2-year-olds completed a VWM task while we recorded neural activity from 19 cortical regions-of-interest identified from a meta-analysis of the adult fMRI literature on VWM. Results showed significant task-specific functional activation near 6 of 19 ROIs, revealing spatial consistency in the brain regions activated in our study and brain regions identified to be part of the VWM network in adult fMRI studies. Working memory related activation was centered on bilateral anterior intraparietal sulcus (aIPS), left temporoparietal junction (TPJ), and left ventral occipital complex (VOC), while visual exploratory measures were associated with activation in right dorsolateral prefrontal cortex, left TPJ, and bilateral IPS. Results show that a distributed brain network underlies functional changes in VWM in infancy, revealing new insights into the neural mechanisms that support infants' improved ability to remember visual information and to detect changes in an on-going visual stream.

Cardiorespiratory fitness and hippocampal volume predict faster episodic associative learning in older adults.

Declining episodic memory is common among otherwise healthy older adults, in part due to negative effects of aging on hippocampal circuits. However, there is significant variability between individuals in severity of aging effects on the hippocampus and subsequent memory decline. Importantly, variability may be influenced by modifiable protective physiological factors such as cardiorespiratory fitness (CRF). More research is needed to better understand which aspects of cognition that decline with aging benefit most from CRF. The current study evaluated the relation of CRF with learning rate on the episodic associative learning (EAL) task, a task designed specifically to target hippocampal-dependent relational binding and to evaluate learning with repeated occurrences. Results show higher CRF was associated with faster learning rate. Larger hippocampal volume was also associated with faster learning rate, though hippocampal volume did not mediate the relationship between CRF and learning rate. Furthermore, to support the distinction between learning item relations and learning higher-order sequences, which declines with aging but is largely reliant on extra-hippocampal learning systems, we found learning rate on the EAL task was not related to motor sequence learning on the alternating serial reaction time task. Motor sequence learning was also not correlated with hippocampal volume. Thus, for the first time, we show that both higher CRF and larger hippocampal volume in healthy older adults are related to enhanced rate of relational memory acquisition.

Three-Dimensional GRE T1ρ mapping of the brain using tailored variable flip-angle scheduling.

PURPOSE: To introduce a new approach called tailored variable flip-angle (VFA) scheduling for SNR-efficient 3D T1ρ mapping of the brain using a magnetization-prepared gradient-echo sequence. METHODS: Simulations were used to assess the relative SNR efficiency, quantitative accuracy, and spatial blurring of tailored VFA scheduling for T1ρ mapping of brain tissue compared with magnetization-prepared angle-modulated partitioned k-space spoiled gradient-echo snapshots (MAPSS), a state-of-the-art technique for accurate 3D gradient-echo T1ρ mapping. Simulations were also used to calculate optimal imaging parameters for tailored VFA scheduling versus MAPSS, without and with nulling of CSF. Four participants were imaged at 3T MRI to demonstrate the feasibility of tailored VFA scheduling for T1ρ mapping of the brain. Using MAPSS as a reference standard, in vivo data were used to validate the relative SNR efficiency and quantitative accuracy of the new approach. RESULTS: Tailored VFA scheduling can provide a 2-fold to 4-fold gain in the SNR of the resulting T1ρ map as compared with MAPSS when using identical sequence parameters while limiting T1ρ quantification errors to 2% or less. In vivo whole-brain 3D T1ρ maps acquired with tailored VFA scheduling had superior SNR efficiency than is achievable with MAPSS, and the SNR efficiency improved with a greater number of views per segment. CONCLUSIONS: Tailored VFA scheduling is an SNR-efficient GRE technique for 3D T1ρ mapping of the brain that provides increased flexibility in choice of imaging parameters compared with MAPSS, which may benefit a variety of applications.

Improved MUSSELS reconstruction for high-resolution multi-shot diffusion weighted imaging.

PURPOSE: MUSSELS is a one-step iterative reconstruction method for multishot diffusion weighted (msDW) imaging. The current work presents an efficient implementation, termed IRLS MUSSELS, that enables faster reconstruction to enhance its utility for high-resolution diffusion MRI studies. METHODS: The recently proposed MUSSELS reconstruction belongs to a new class of parallel imaging-based methods that recover artifact-free DWIs from msDW data without needing phase compensation. The reconstruction is achieved via structured low-rank matrix completion algorithms, which are computationally demanding due to the large size of the Hankel matrices and their associated computations involving singular value decompositions. Because of this, computational demands of the MUSSELS reconstruction scales as the matrix size and the number of shots increases, which hinders its practical utility for high-resolution applications. In this work, we derive a computationally efficient MUSSELS formulation by modifying the iterative reweighted least squares (IRLS) method that were proposed earlier to solve such problems. Using whole-brain in vivo data, we show the utility of the IRLS MUSSELS for routine high-resolution studies with reduced computational burden. RESULTS: IRLS MUSSELS provides about five times faster reconstruction for matrix sizes 192 × 192 and 256 × 256 compared to the earlier MUSSELS implementation. The widely employed conjugate symmetry priors can also be incorporated into IRLS MUSSELS to reduce blurring of the partial Fourier acquisitions, without incurring much computational burden. CONCLUSIONS: The proposed method is observed to be computationally efficient to enable routine high-resolution studies. The computational complexity matches the traditional msDWI reconstruction methods and provides improved reconstruction results with the additional constraints.

SMS MUSSELS: A navigator-free reconstruction for simultaneous multi-slice-accelerated multi-shot diffusion weighted imaging.

PURPOSE: To introduce a novel reconstruction method for simultaneous multi-slice (SMS)-accelerated multi-shot diffusion weighted imaging (ms-DWI). METHODS: SMS acceleration using blipped-CAIPI schemes have been proposed to speed up the acquisition of ms-DWIs. The reconstruction of the data requires (a) phase compensation to combine data from different shots and (b) slice unfolding to separate the data of different slices. The traditional approaches first estimate the phase maps corresponding to each shot and slice which are then employed to iteratively recover the slice unfolded DWIs without phase artifacts. In contrast, the proposed reconstruction directly recovers the slice-unfolded k-space data of the multiple shots for each slice in a single-step recovery scheme. The proposed method is enabled by the low-rank property inherent in the k-space samples of ms-DW acquisition. This enabled to formulate a joint recovery scheme that simultaneously (a) unfolds the k-space data of each slice using a SENSE-based scheme and (b) recover the missing k-space samples in each slice of the multi-shot acquisition employing a structured low-rank matrix completion. Additional smoothness regularization is also utilized for higher acceleration factors. The proposed joint recovery is tested on simulated and in vivo data and compared to similar un-navigated methods. RESULTS: Our experiments show effective slice unfolding and successful recovery of DWIs with minimal phase artifacts using the proposed method. The performance is comparable to existing methods at low acceleration factors and better than existing methods for higher acceleration factors. CONCLUSIONS: For the slice accelerations considered in this study, the proposed method can successfully recover DWIs from SMS-accelerated ms-DWI acquisitions.

R1ρ sensitivity to pH and other compounds at clinically accessible spin-lock fields in the presence of proteins.

Numerous human diseases involve abnormal metabolism, and proton exchange is an effective source of magnetic resonance imaging (MRI) contrast for assessing metabolism. One MRI technique that capitalizes on proton exchange is R1 relaxation in the rotating frame (R1ρ ). Here, we investigated the sensitivity of R1ρ to various proton-exchange mechanisms at spin-lock pulses within Food and Drug Administration (FDA) safety guidelines for radiofrequency-induced heating. We systematically varied pH known to change the rate of proton exchange as well as the glucose and lysine concentrations, thus changing the number of amide, hydroxyl and amine exchangeable sites in a series of egg-white albumin phantoms. The resulting effects on quantitative relaxation time measurements of R1ρ , R1 and R2 were observed at 3 T. Using spin-lock amplitudes available for human imaging (less than 23.5 µT) at near physiologic temperatures, we found R1ρ was more sensitive to physiologic changes in pH than to changes in glucose and lysine concentrations. In addition, R1ρ was more sensitive to pH changes than R1 and R2 . Models of proton exchange fitted to the relaxation measurements suggest that amide groups were the primary source of pH sensitivity. Together, these experiments suggest an optimal spin-lock amplitude for measuring pH changes while not exceeding FDA-subject heating limitations.

Comparison of T1Rho MRI, Glucose Metabolism, and Amyloid Burden Across the Cognitive Spectrum: A Pilot Study.

OBJECTIVE: The pathological cascades associated with the development of Alzheimer's disease (AD) have a common element: acidosis. T1rho MRI is a pH-sensitive measure, with higher values associated with greater neuropathological burden. The authors investigated the relationship between T1rho imaging and AD-associated pathologies as determined by available diagnostic imaging techniques. METHODS: Twenty-seven participants (men, N=13, women, N=14; ages 55-90) across the cognitive spectrum (healthy control subjects [HCs] with normal cognition, N=17; participants with mild cognitive impairment [MCI], N=7; participants with mild AD, N=3) underwent neuropsychological testing, MRI (T1-weighted and T1rho [spin-lattice relaxation time in the rotating frame]), and positron emission tomography imaging ([11C]Pittsburg compound B for amyloid burden [N=26] and [18F]fluorodeoxyglucose for cerebral glucose metabolism [N=12]). The relationships between global T1rho values and neuropsychological, demographic, and imaging measures were explored. RESULTS: Global mean and median T1rho were positively associated with age. After controlling for age, higher global T1rho was associated with poorer cognitive function, poorer memory function (immediate and delayed memory scores), higher amyloid burden, and more abnormal cerebral glucose metabolism. Regional T1rho values, when controlling for age, significantly differed between HCs and participants with MCI or AD in select frontal, cingulate, and parietal regions. CONCLUSIONS: Higher T1rho values were associated with greater cognitive impairment and pathological burden. T1rho, a biomarker that varies according to a feature common to each cascade rather than one that is unique to a particular pathology, has the potential to serve as a metric of neuropathology, theoretically providing a measure for assessing pathological status and for monitoring the neurodegeneration trajectory.

Cystitis-induced bladder pain is Toll-like receptor 4 dependent in a transgenic autoimmune cystitis murine model: a MAPP Research Network animal study.

Altered Toll-like receptor (TLR)4 activation has been identified in several chronic pain conditions but has not been well studied in interstitial cystitis/bladder pain syndrome (IC/BPS). Our previously published human studies indicated that patients with IC/BPS present altered systemic TLR4-mediated inflammatory responses, which were significantly correlated with reported pain severity. In the present study, we sought to determine whether altered TLR4 activation plays a role in pelvic/bladder pain seen in patients with IC/BPS using our validated IC/BPS-like transgenic autoimmune cystitis model (URO-OVA). URO-OVA mice developed responses consistent with pelvic and bladder pain after cystitis induction, which was associated with increased splenocyte production of TLR4-mediated proinflammatory cytokines IL-1ß, IL-6, and TNF-α. Increased spinal expression of mRNAs for proinflammatory cytokines IL-6 and TNF-α, glial activation markers CD11b and glial fibrillary acidic protein, and endogenous TLR4 ligand high mobility group box 1 was also observed after cystitis induction. Compared with URO-OVA mice, TLR4-deficient URO-OVA mice developed significantly reduced nociceptive responses, although similar bladder inflammation and voiding dysfunction, after cystitis induction. Intravenous administration of TAK-242 (a TLR4-selective antagonist) significantly attenuated nociceptive responses in cystitis-induced URO-OVA mice, which was associated with reduced splenocyte production of TLR4-mediated IL-1ß, IL-6, and TNF-α as well as reduced spinal expression of mRNAs for IL-6, TNF-α, CD11b, glial fibrillary acidic protein, and high mobility group box 1. Our results indicate that altered TLR4 activation plays a critical role in bladder nociception independent of inflammation and voiding dysfunction in the URO-OVA model, providing a potential mechanistic insight and therapeutic target for IC/BPS pain.