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Background: It is generally believed that activation in functional magnetic resonance imaging (fMRI) is restricted to gray matter. Despite this, a number of studies have reported white matter activation, particularly when the corpus callosum is targeted using interhemispheric transfer tasks. These findings suggest that fMRI signals may not be neatly confined to gray matter tissue. In the current experiment, 4 T fMRI was employed to evaluate whether it is possible to detect white matter activation. We used an interhemispheric transfer task modelled after neurological studies of callosal disconnection. It was hypothesized that white matter activation could be detected using fMRI.Results: Both group and individual data were considered. At liberal statistical thresholds (p < 0.005, uncorrected), group level activation was detected in the isthmus of the corpus callosum. This region connects the superior parietal cortices, which have been implicated previously in interhemispheric transfer. At the individual level, five of the 24 subjects (21%) had activation clusters that were located primarily within the corpus callosum. Consistent with the group results, the clusters of all five subjects were located in posterior callosal regions. The signal time courses for these clusters were comparable to those observed for task related gray matter activation.Conclusion: The findings support the idea that, despite the inherent challenges, fMRI activation can be detected in the corpus callosum at the individual level. Future work is needed to determine whether the detection of this activation can be improved by utilizing higher spatial resolution, optimizing acquisition parameters, and analyzing the data with tissue specific models of the hemodynamic response. The ability to detect white matter fMRI activation expands the scope of basic and clinical brain mapping research, and provides a new approach for understanding brain connectivity. [ABSTRACT FROM AUTHOR]

Background: The Cubresa Spark is a novel benchtop silicon-photomultiplier (SiPM)-based preclinical SPECT system. SiPMs in SPECT significantly improve resolution and reduce detector size compared to preclinical cameras with photomultiplier tubes requiring highly magnifying collimators. The NEMA NU 1 Standard for Performance Measurements of Gamma Cameras provides methods that can be readily applied or extended to characterize preclinical cameras with minor modifications. The primary objective of this study is to characterize the Spark according to the NEMA NU 1-2018 standard to gain insight into its nuclear medicine imaging capabilities. The secondary objective is to validate a GATE Monte Carlo simulation model of the Spark for use in preclinical SPECT studies., Methods: NEMA NU 1-2018 guidelines were applied to characterize the Spark's intrinsic, system, and tomographic performance with single- and multi-pinhole collimators. Phantoms were fabricated according to NEMA specifications with deviations involving high-resolution modifications. GATE was utilized to model the detector head with the single-pinhole collimator, and NEMA measurements were employed to tune and validate the model. Single-pinhole and multi-pinhole SPECT data were reconstructed with the Software for Tomographic Image Reconstruction and HiSPECT, respectively., Results: The limiting intrinsic resolution was measured as 0.85 mm owing to a high-resolution SiPM array combined with a 3 mm-thick scintillation crystal. The average limiting tomographic resolution was 1.37 mm and 1.19 mm for the single- and multi-pinhole collimators, respectively, which have magnification factors near unity at the center of rotation. The maximum observed count rate was 15,400 cps, and planar sensitivities of 34 cps/MBq and 150 cps/MBq were measured at the center of rotation for the single- and multi-pinhole collimators, respectively. All simulated tests agreed well with measurement, where the most considerable deviations were below 7%., Conclusions: NEMA NU 1-2018 standards determined that a SiPM detector mitigates the need for highly magnifying pinhole collimators while preserving detailed information in projection images. Measured and simulated NEMA results were highly comparable with differences on the order of a few percent, confirming simulation accuracy and validating the GATE model. Of the collimators initially provided with the Spark, the multi-pinhole collimator offers high resolution and sensitivity for organ-specific imaging of small animals, and the single-pinhole collimator enables high-resolution whole-body imaging of small animals., (© 2023. The Author(s).)

Objective: Extensive blood-brain barrier (BBB) leakage has been linked to cognitive impairment in SLE. This study aimed to examine the associations of brain functional connectivity (FC) with cognitive impairment and BBB dysfunction among patients with SLE., Methods: Cognitive function was assessed by neuropsychological testing (n = 77). Resting-state FC (rsFC) between brain regions, measured by functional MRI (n = 78), assessed coordinated neural activation in 131 regions across five canonical brain networks. BBB permeability was measured by dynamic contrast-enhanced MRI (n = 61). Differences in rsFC were compared between SLE patients with cognitive impairment (SLE-CI) and those with normal cognition (SLE-NC), between SLE patients with and without extensive BBB leakage, and with healthy controls., Results: A whole-brain rsFC comparison found significant differences in intra-network and inter-network FC in SLE-CI vs SLE-NC patients. The affected connections showed a reduced negative rsFC in SLE-CI compared with SLE-NC and healthy controls. Similarly, a reduced number of brain-wide connections was found in SLE-CI patients compared with SLE-NC (P = 0.030) and healthy controls (P = 0.006). Specific brain regions had a lower total number of brain-wide connections in association with extensive BBB leakage (P = 0.011). Causal mediation analysis revealed that 64% of the association between BBB leakage and cognitive impairment in SLE patients was mediated by alterations in FC., Conclusion: SLE patients with cognitive impairment had abnormalities in brain rsFC which accounted for most of the association between extensive BBB leakage and cognitive impairment., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: Cognitive impairment is common in patients with SLE but the cause is unknown. The current cross-sectional study examined the association between select SLE-related autoantibodies, other serological biomarkers and extensive blood-brain barrier (BBB) leakage in patients with SLE with and without cognitive impairment. In addition, we determined whether the relationship between SLE autoantibodies, other biomarkers and cognitive impairment differed depending on the presence or absence of concurrent extensive BBB leakage., Methods: Consecutive patients with SLE, recruited from a single academic medical centre, underwent formal neuropsychological testing for assessment of cognitive function. On the same day, BBB permeability was determined using dynamic contrast-enhanced MRI scanning. SLE autoantibodies and other serological biomarkers were measured. Regression modelling was used to determine the association between cognitive impairment, extensive BBB leakage and autoantibodies/biomarkers., Results: There were 102 patients with SLE; 90% were female and 88% were Caucasian, with a mean±SD age of 48.9±13.8 years. The mean±SD SLE disease duration was 14.8±11.0 years. Impairment in one or more cognitive tests was present in 47 of 101 (47%) patients and included deficits in information processing speed (9%), attention span (21%), new learning (8%), delayed recall (15%) and executive abilities (21%). Extensive BBB leakage was present in 20 of 79 (25%) patients and was associated with cognitive impairment (15 of 20 (75%) vs 24 of 59 (41%); p=0.01) and shorter disease duration (median (IQR): 7 (8-24 years) vs 15 (2-16 years); p=0.02). No serological parameters were associated with extensive BBB leakage and there was no statistically significant association between cognitive impairment and circulating autoantibodies even after adjusting for BBB leakage., Conclusions: Extensive BBB leakage alone was associated with cognitive impairment. These findings suggest that BBB leakage is an important contributor to cognitive impairment, regardless of circulating SLE-related autoantibodies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Multiparametric MRI (mp-MRI) is a widely used tool for diagnosing and staging prostate cancer. The purpose of this study was to evaluate whether transfer learning, unsupervised pre-training and test-time augmentation significantly improved the performance of a convolutional neural network (CNN) for pixel-by-pixel prediction of cancer vs. non-cancer using mp-MRI datasets., Methods: 154 subjects undergoing mp-MRI were prospectively recruited, 16 of whom subsequently underwent radical prostatectomy. Logistic regression, random forest and CNN models were trained on mp-MRI data using histopathology as the gold standard. Transfer learning, unsupervised pre-training and test-time augmentation were used to boost CNN performance. Models were evaluated using Dice score and area under the receiver operating curve (AUROC) with leave-one-subject-out cross validation. Permutation feature importance testing was performed to evaluate the relative value of each MR contrast to CNN model performance. Statistical significance (p<0.05) was determined using the paired Wilcoxon signed rank test with Benjamini-Hochberg correction for multiple comparisons., Results: Baseline CNN outperformed logistic regression and random forest models. Transfer learning and unsupervised pre-training did not significantly improve CNN performance over baseline; however, test-time augmentation resulted in significantly higher Dice scores over both baseline CNN and CNN plus either of transfer learning or unsupervised pre-training. The best performing model was CNN with transfer learning and test-time augmentation (Dice score of 0.59 and AUROC of 0.93). The most important contrast was apparent diffusion coefficient (ADC), followed by Ktrans and T2, although each contributed significantly to classifier performance., Conclusions: The addition of transfer learning and test-time augmentation resulted in significant improvement in CNN segmentation performance in a small set of prostate cancer mp-MRI data. Results suggest that these techniques may be more broadly useful for the optimization of deep learning algorithms applied to the problem of semantic segmentation in biomedical image datasets. However, further work is needed to improve the generalizability of the specific model presented herein., Competing Interests: Conflict of Interest Drs. Guida, Bowen, Beyea and Clarke acknowledge research funding and support from GE Healthcare., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Nonalcoholic fatty liver disease (NAFLD) is a growing health problem, and a major challenge in NAFLD management is identifying which patients are at risk of progression to more serious disease. Simple measurements of liver fat content are not strong predictors of clinical outcome, but biomarkers related to fatty acid composition (ie, saturated vs. unsaturated fat) may be more effective. MR spectroscopic imaging (MRSI) methods allow spatially resolved, whole-liver measurements of chemical composition but are traditionally limited by slow acquisition times. In this work we present an accelerated MRSI acquisition based on spin echo single point imaging (SE-SPI), which, using appropriate sampling and compressed sensing reconstruction, allows free-breathing acquisition in a mouse model of fatty liver disease. After validating the technique's performance in oil/water phantoms, we imaged mice that had received a normal diet or a methionine and choline deficient (MCD) diet, some of which also received supplemental injections of iron to mimic hepatic iron overload. SE-SPI was more resistant to the line-broadening effects of iron than single-voxel spectroscopy measurements, and was consistently able to measure the amplitudes of low-intensity spectral peaks that are important to characterizing fatty acid composition. In particular, in the mice receiving the MCD diet, SE-SPI showed a significant decrease in a metric associated with unsaturated fat, which is consistent with the literature. This or other related metrics may therefore offer more a specific biomarker of liver health than fat content alone. This preclinical study is an important precursor to clinical testing of the proposed method. MR-based quantification of fatty acid composition may allow for improved characterization of non-alcoholic fatty liver disease. A spectroscopic imaging method with appropriate sampling strategy allows whole-liver mapping of fat composition metrics in a free-breathing mouse model. Changes in metrics like the surrogate unsaturation index (UIs) are visible in mice receiving a diet which induces fat accumulation in the liver, as compared to a normal diet; such metrics may prove useful in future clinical studies of liver disease., (© 2020 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.)

Objectives: To examine the association between blood-brain barrier (BBB) integrity, brain volume and cognitive dysfunction in adult patients with systemic lupus erythematosus (SLE)., Methods: A total of 65 ambulatory patients with SLE and 9 healthy controls underwent dynamic contrast-enhanced MRI scanning, for quantitative assessment of BBB permeability. Volumetric data were extracted using the VolBrain pipeline. Global cognitive function was evaluated using a screening battery consisting of tasks falling into five broad cognitive domains, and was compared between patients with normal versus extensive BBB leakage., Results: Patients with SLE had significantly higher levels of BBB leakage compared with controls (p=0.04). Extensive BBB leakage (affecting over >9% of brain volume) was identified only in patients with SLE (16/65; 24.6%), who also had smaller right and left cerebral grey matter volumes compared with controls (p=0.04). Extensive BBB leakage was associated with lower global cognitive scores (p=0.02), and with the presence of impairment on one or more cognitive tasks (p=0.01)., Conclusion: Our findings provide evidence for a link between extensive BBB leakage and changes in both brain structure and cognitive function in patients with SLE. Future studies should investigate the mechanisms underlying BBB-mediated cognitive impairment, validate the diagnostic utility of BBB imaging, and determine the potential of targeting the BBB as a therapeutic strategy in patients with SLE., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Bipolar disorder affects approximately 2% of the population and is typically characterized by recurrent episodes of mania and depression. While some patients achieve remission using mood-stabilizing treatments, a significant proportion of patients show progressive changes in symptomatology over time. Bipolar progression is diverse in nature and may include a treatment-resistant increase in the frequency and severity of episodes, worse psychiatric and functional outcomes, and a greater risk of suicide. The mechanisms underlying bipolar disorder progression remain poorly understood and there are currently no biomarkers for identifying patients at risk. The objective of this study was to explore the potential of blood-brain barrier (BBB) imaging as such a biomarker, by acquiring the first imaging data of BBB leakage in bipolar patients, and evaluating the potential association between BBB dysfunction and bipolar symptoms. To this end, a cohort of 36 bipolar patients was recruited through the Mood Disorders Clinic (Nova Scotia Health Authority, Canada). All patients, along with 14 control subjects (matched for sex, age and metabolic status), underwent contrast-enhanced dynamic MRI scanning for quantitative assessment of BBB leakage as well as clinical and psychiatric evaluations. Outlier analysis has identified a group of 10 subjects with significantly higher percentages of brain volume with BBB leakage (labeled the "extensive BBB leakage" group). This group consisted exclusively of bipolar patients, while the "normal BBB leakage" group included the entire control cohort and the remaining 26 bipolar subjects. Among the bipolar cohort, patients with extensive BBB leakage were found to have more severe depression and anxiety, and a more chronic course of illness. Furthermore, all bipolar patients within this group were also found to have co-morbid insulin resistance, suggesting that insulin resistance may increase the risk of BBB dysfunction in bipolar patients. Our findings demonstrate a clear link between BBB leakage and greater psychiatric morbidity in bipolar patients and highlight the potential of BBB imaging as a mechanism-based biomarker for bipolar disorder progression., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interests to disclose., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Dynamic contrast enhanced (DCE) magnetic resonance imaging (MRI) is a method of temporal imaging that is commonly used to aid in prostate cancer (PCa) diagnosis and staging. Typically, machine learning models designed for the segmentation and detection of PCa will use an engineered scalar image called K trans to summarize the information in the DCE time-series images. This work proposes a new model that amalgamates the U-net and the convGRU neural network architectures for the purpose of interpreting DCE time-series in a temporal and spatial basis for segmenting PCa in MR images. Ultimately, experiments show that the proposed model using the DCE time-series images can outperform a baseline U-net segmentation model using K trans . However, when other types of scalar MR images are considered by the models, no significant advantage is observed for the proposed model., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The American College of Rheumatology's case definitions for 19 neuropsychiatric syndromes in systemic lupus erythematosus (SLE) constitute a comprehensive classification of nervous system events in this disease. However, additional strategies are needed to determine whether a neuropsychiatric syndrome is attributable to SLE versus a competing comorbidity. Cognitive function is a clinical surrogate of overall brain health, with applications in both diagnosis and determination of clinical outcomes. Ischemic and inflammatory mechanisms are both key components of the immunopathogenesis of neuropsychiatric SLE (NPSLE), including abnormalities of the blood-brain barrier and autoantibody-mediated production of proinflammatory cytokines. Advances in neuroimaging provide a platform to assess novel disease mechanisms in a noninvasive way. The convergence of more rigorous clinical characterization, validation of biomarkers, and brain neuroimaging provides opportunities to determine the efficacy of novel targeted therapies in the treatment of NPSLE., (© 2018, American College of Rheumatology.)

Objective: Purely phase-encoded techniques such as single point imaging (SPI) are generally unsuitable for in vivo imaging due to lengthy acquisition times. Reconstruction of highly undersampled data using compressed sensing allows SPI data to be quickly obtained from animal models, enabling applications in preclinical cellular and molecular imaging., Materials and Methods: TurboSPI is a multi-echo single point technique that acquires hundreds of images with microsecond spacing, enabling high temporal resolution relaxometry of large-R 2 * systems such as iron-loaded cells. TurboSPI acquisitions can be pseudo-randomly undersampled in all three dimensions to increase artifact incoherence, and can provide prior information to improve reconstruction. We evaluated the performance of CS-TurboSPI in phantoms, a rat ex vivo, and a mouse in vivo., Results: An algorithm for iterative reconstruction of TurboSPI relaxometry time courses does not affect image quality or R 2 * mapping in vitro at acceleration factors up to 10. Imaging ex vivo is possible at similar acceleration factors, and in vivo imaging is demonstrated at an acceleration factor of 8, such that acquisition time is under 1 h., Conclusions: Accelerated TurboSPI enables preclinical R 2 * mapping without loss of data quality, and may show increased specificity to iron oxide compared to other sequences.

Purpose: Functional MRI (fMRI) is becoming increasingly integrated into clinical practice for presurgical mapping. Current efforts are focused on validating data quality, with reliability being a major factor. In this paper, we demonstrate the utility of a recently developed approach that uses receiver operating characteristic-reliability (ROC-r) to: (1) identify reliable versus unreliable data sets; (2) automatically select processing options to enhance data quality; and (3) automatically select individualised thresholds for activation maps., Methods: Presurgical fMRI was conducted in 16 patients undergoing surgical treatment for brain tumours. Within-session test-retest fMRI was conducted, and ROC-reliability of the patient group was compared to a previous healthy control cohort. Individually optimised preprocessing pipelines were determined to improve reliability. Spatial correspondence was assessed by comparing the fMRI results to intraoperative cortical stimulation mapping, in terms of the distance to the nearest active fMRI voxel., Results: The average ROC-r reliability for the patients was 0.58±0.03, as compared to 0.72±0.02 in healthy controls. For the patient group, this increased significantly to 0.65±0.02 by adopting optimised preprocessing pipelines. Co-localisation of the fMRI maps with cortical stimulation was significantly better for more reliable versus less reliable data sets (8.3±0.9 vs 29±3 mm, respectively)., Conclusions: We demonstrated ROC-r analysis for identifying reliable fMRI data sets, choosing optimal postprocessing pipelines, and selecting patient-specific thresholds. Data sets with higher reliability also showed closer spatial correspondence to cortical stimulation. ROC-r can thus identify poor fMRI data at time of scanning, allowing for repeat scans when necessary. ROC-r analysis provides optimised and automated fMRI processing for improved presurgical mapping., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Recent evidence shows that functional magnetic resonance imaging (fMRI) can detect activation in white matter (WM). Such advances have important implications for understanding WM dysfunction. A key step in linking neuroimaging advances to the evaluation of clinical disorders is to examine whether WM activation can be detected at the individual level during clinical tests associated with WM function. We used an adapted Symbol Digit Modalities Test (SDMT) in a 4T fMRI study of healthy adults., Results: RESULTS from 17 healthy individuals revealed WM activation in 88% of participants (15/17). The activation was in either the corpus callosum (anterior and/or posterior) or internal capsule (left and/or right)., Conclusions: The findings link advances in fMRI to an established clinical test of WM function. Future work should focus on evaluating patients with WM dysfunction.

Purpose: Functional MRI (fMRI) techniques that can provide excellent blood oxygen level dependent contrast, rapid whole brain imaging, and minimal spatial distortion are in demand. This study explored whether fMRI sensitivity can be improved through the use of compressed sensing (CS) reconstruction of variable density spiral fMRI., Methods: Three different CS-reconstructed 1-shot variable density spirals were explored (corresponding to 28%, 35%, and 46% under-sampling), and compared with conventional 1-shot and 2-shot Archimedean spirals acquired using matched echo time and volume repetition time. fMRI maps were reconstructed with or without CS MRI and sensitivity was compared using identically matched voxels., Results: The results demonstrated that an l1 -norm based CS reconstruction only led to an increase in functional contrast when applied to 28% under-sampled data. A whole brain t-contrast map revealed that 2-shot uniformly sampled spiral and 28% under-sampled spiral data reconstructed with CS yield equivalent sensitivity, even with matched echo time and volume repetition time, Conclusion: VD spiral exhibits a useful operating range, in the region of 25-30% under-sampling, for which CS reconstruction can be used to increase the sensitivity of fMRI to brain activity. Using CS, VD acquisitions achieve the same sensitivity as 2-shot Archimedean acquisitions, but require only a single shot., (Copyright © 2013 Wiley Periodicals, Inc.)

Many studies have investigated test-retest reliability of active voxel classification for fMRI, which is increasingly important for emerging clinical applications. The implicit impact of voxel-wise thresholding on this type of reliability has previously been under-appreciated. This has had two detrimental effects: (1) reliability studies use different fixed thresholds, making comparison of results is challenging; (2) typical studies do not assess reliability at the individual level, which could provide information for selecting activation thresholds. To show the limitations of traditional fixed-threshold approaches, we investigated the threshold dependence of fMRI reliability measures, with the goal of developing an automated threshold selection routine. For this purpose, we demonstrated threshold dependence of both novel (ROC-reliability or ROC-r) and established (Rombouts overlap or RR) reliability measures. Both methods rely minimally on statistical assumptions, and provide a data-driven summary of the threshold-reliability relationship. We applied these methods to data from eight subjects performing a simple finger tapping task across repeated fMRI sessions. We showed that the reliability measures varied dramatically with threshold. This variation depended strongly on the individual tested. Finally, we demonstrated novel procedures using ROC-r and overlap analysis to optimize thresholds on a case-by-case basis. Ultimately, a method to determine robust individual-level activation maps represents a critical advance for fMRI as a diagnostic tool., (Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.)

Background: One of the major disadvantages of mandibular distraction osteogenesis (MDO) is the prolonged time required for consolidation of the regenerate bone. The objective of the present study is to perform a contemporary review of various adjuvant therapies to enhance bone consolidation in MDO., Methods: A PubMed search for articles related to MDO, along with the references of those articles, was performed. Inclusion and exclusion criteria were applied to all experimental studies assessing adjuvant therapies to enhance bone consolidation., Results: A total of 1414 titles and abstracts were initially reviewed; 61 studies were included for full review. Many studies involved growth factors, hormones, pharmacological agents, gene therapy, and stem cells. Other adjuvant therapies included mechanical stimulation, laser therapy, and hyperbaric oxygen. Majority of the studies demonstrated positive bone healing effects and thus adjuvant therapies remain a viable strategy to enhance and hasten the consolidation period., Conclusion: Although most studies have demonstrated promising results, many questions still remain, such as optimal amount, timing, and delivery methods required to stimulate the most favorable bone regeneration. As well, further studies comparing various adjuvant therapies and documentation of long-term adverse effects are required prior to clinical application., (Copyright © 2013 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Functional magnetic resonance imaging (fMRI) activation in white matter is controversial. Given that many of the studies that report fMRI activation in white matter used high field MRI systems, we investigated the field strength dependence of sensitivity to white matter fMRI activation. In addition, we evaluated the temporal signal to noise ratio (tSNR) of the different tissue types as a function of field strength. Data were acquired during a motor task (finger tapping) at 1.5 T and 4 T. Group and individual level activation results were considered in both the sensorimotor cortex and the posterior limb of the internal capsule. We found that sensitivity increases associated with field strength were greater for white matter than gray matter. The analysis of tSNR suggested that white matter might be less susceptible to increases in physiological noise related to increased field strength. We therefore conclude that high field MRI may be particularly advantageous for fMRI studies aimed at investigating activation in both gray and white matter.

Degradable, bioceramic bone implants made of calcium polyphosphate (CPP) hold potential for controlled release of therapeutic agents in the treatment of localized bone disease. Magnetic resonance imaging techniques for non-invasively mapping fluid distribution, T(1) and T(2) relaxation times and the apparent diffusion coefficient were performed in conjunction with a drug elution protocol to resolve free and bound water components within the material microstructure in two CPP formulations (G1 and G2). The T(2) maps provided the most accurate estimates of free and bound water, and showed that G1 disks contained a detectable free water component at all times, with drug release dominated by a Fickian diffusion mechanism. Drug release from G2 disks was characterized by a combined diffusional/structural relaxation mechanism, which may be related to the gradual infiltration of a free water component associated with swelling and/or chemical degradation., (Copyright © 2012 Crown Copyright National Research Council. Published by Elsevier Ltd.. All rights reserved.)

Recent developments have shown that it is possible to detect functional magnetic resonance imaging (fMRI) activation in white matter (WM). Enhanced sensitivity to WM fMRI signals has been associated with the asymmetric spin echo (ASE) spiral sequence. The ASE spiral sequence produces three consecutive images that have equal blood-oxygen level-dependent (BOLD) contrast but increasing T(2) contrast. The current study evaluated whether ASE spiral sensitivity differed between white and gray matter in the corpus callosum, superior parietal lobes, cingulate gyrus, and inferior frontal lobes. Contrast and noise were compared across the three images for each region. Results showed increasing gains in functional contrast in both white and gray matter as a function of T(2) contrast. The third image, with the most T(2) contrast, showed the largest increase in contrast, while changes in noise were maintained. The results suggest that ASE spiral increases fMRI sensitivity globally through the addition of T(2) weighted contrast., (Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.)

Background: There is growing evidence for the idea of fMRI activation in white matter. In the current study, we compared hemodynamic response functions (HRF) in white matter and gray matter using 4 T fMRI. White matter fMRI activation was elicited in the isthmus of the corpus callosum at both the group and individual levels (using an established interhemispheric transfer task). Callosal HRFs were compared to HRFs from cingulate and parietal activation., Results: Examination of the raw HRF revealed similar overall response characteristics. Finite impulse response modeling confirmed that the WM HRF characteristics were comparable to those of the GM HRF, but had significantly decreased peak response amplitudes., Conclusions: Overall, the results matched a priori expectations of smaller HRF responses in white matter due to the relative drop in cerebral blood flow (CBF) and cerebral blood volume (CBV). Importantly, the findings demonstrate that despite lower CBF and CBV, white matter fMRI activation remained within detectable ranges at 4 T.

Susceptibility field gradients (SFGs) cause problems for functional magnetic resonance imaging (fMRI) in regions like the orbital frontal lobes, leading to signal loss and image artifacts (signal displacement and "pile-up"). Pulse sequences with spiral-in k-space trajectories are often used when acquiring fMRI in SFG regions such as inferior/medial temporal cortex because it is believed that they have improved signal recovery and decreased signal displacement properties. Previously postulated theories explain differing reasons why spiral-in appears to perform better than spiral-out; however it is clear that multiple mechanisms are occurring in parallel. This study explores differences in spiral-in and spiral-out images using human and phantom empirical data, as well as simulations consistent with the phantom model. Using image simulations, the displacement of signal was characterized using point spread functions (PSFs) and target maps, the latter of which are conceptually inverse PSFs describing which spatial locations contribute signal to a particular voxel. The magnitude of both PSFs and target maps was found to be identical for spiral-out and spiral-in acquisitions, with signal in target maps being displaced from distant regions in both cases. However, differences in the phase of the signal displacement patterns that consequently lead to changes in the intervoxel phase coherence were found to be a significant mechanism explaining differences between the spiral sequences. The results demonstrate that spiral-in trajectories do preserve more total signal in SFG regions than spiral-out; however, spiral-in does not in fact exhibit decreased signal displacement. Given that this signal can be displaced by significant distances, its recovery may not be preferable for all fMRI applications., (Copyright © 2012 Elsevier Inc. All rights reserved.)

This work proposes the use of TurboSPI, a multi-echo single point imaging sequence, for the quantification of labeled cells containing moderate to high concentrations of iron oxide contrast agent. At each k-space location, TurboSPI acquires several hundred time points during a spin echo, permitting reliable relaxation rate mapping of large-R(2)(∗) materials. An automatic calibration routine optimizes image quality by promoting coherent alignment of spin and stimulated echoes throughout the multi-echo train, and this calibration is sufficiently robust for in vivo applications. In vitro relaxation rate measurements of SPIO-loaded cervical cancer cells exhibit behavior consistent with theoretical predictions of the static dephasing regime in the spin echo case; the relaxivity measured with TurboSPI was 10.47±2.3 s(-1)/mG, comparable to the theoretical value of 10.78 s(-1)/mG. Similar measurements of micron-sized iron oxide particles (0.96 μm and 1.63 μm diameter) show a reduced relaxivity of 8.06±0.68 s(-1)/mG and 7.13±0.31 s(-1)/mG respectively, indicating that the static dephasing criterion was not met. Nonetheless, accurate quantification of such particles is demonstrated up to R(2)(∗)=900 s(-1), with a potentially higher upper limit for loaded cells having a more favorable R(2)('):R(2) ratio. Based on the cells used in this study, reliable quantification of cells loaded with 10 pg of iron per cell should be possible up to a density of 27 million cells/mL. Such quantification will be of crucial importance to the development of longitudinal monitoring for cellular therapy and other procedures using iron-labeled cells., (Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.)

Functional imaging has potential for tracking changes in cognition during the onset and evolution of epilepsy. Although the concept of imaging such changes over time is an exciting new direction, feasibility remains an open question. The current article outlines a case example in which functional magnetic resonance imaging (fMRI) and event-related potentials (ERPs) were used to monitor memory changes before and after selective temporal lobe resection. From this example, three key methodologic challenges for new-onset epilepsy are identified and discussed. The first challenge relates to the interpretation of results in regions near epileptogenic tissue. We argue that this is best addressed by collecting information from multiple modalities to test for convergent evidence. The second challenge relates to optimizing the methods for sensitivity to detecting changes. In this case, enhanced imaging methods and a region-of-interest approach provide necessary focus. The third and final challenge relates to the practical difficulties of conducting research in new-onset epilepsy cases. We suggest that greater integration of imaging research within the clinical setting is needed., (Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.)

Background: Functional magnetic resonance imaging (fMRI) in white matter has long been considered controversial. Recently, this viewpoint has been challenged by an emerging body of evidence demonstrating white matter activation in the corpus callosum. The current study aimed to determine whether white matter activation could be detected outside of the corpus callosum, in the internal capsule. Data were acquired from a 4 T MRI using a specialized asymmetric spin echo spiral sequence. A motor task was selected to elicit activation in the posterior limb of the internal capsule., Results: White matter fMRI activation was examined at the individual and group levels. Analyses revealed that activation was present in the posterior limb of the internal capsule in 80% of participants. These results provide further support for white matter fMRI activation., Conclusions: The ability to visualize functionally active tracts has strong implications for the basic scientific study of connectivity and the clinical assessment of white matter disease.

Introduction: The idea of fMRI activation in white matter (WM) is controversial. Our recent work has used two different approaches to investigate whether there is evidence for WM fMRI. The first approach used words and faces to elicit interhemispheric transfer activation in the posterior corpus callosum (Sperry task). The second approach used checkerboard stimuli to elicit similar activation in the anterior corpus callosum (Poffenberger task). Using these different tasks, it has been possible to detect WM activation in different regions. In the current study, we report the results of a critical experiment: demonstrating that callosal activation can be experimentally manipulated within the same set of individuals., Methods: All subjects completed both the Sperry and Poffenberger tasks. Functional MRI data were acquired at 4T, using an asymmetric spin echo spiral sequence. Data were analyzed with FSL using a model-based approach. Analyses focused on group and individual activations in WM., Results and Discussion: Corpus callosum activation was elicited for both tasks, with activation varying according to task type. A statistical contrast of the two tasks revealed posterior callosal activation for the Sperry task and anterior callosal activation for the Poffenberger task. The Sperry task showed activation in the isthmus and middle body of the corpus callosum at the group level and in 100% of subjects. The Poffenberger task showed activation in the genu and middle body of the corpus callosum at the group level and in 94% of subjects. The WM activation replicated prior results, with the additional strength of functional mapping within the same group of individuals., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Recently, functional magnetic resonance imaging (fMRI) activation has been detected in white matter, despite the widely-held belief that fMRI activation is restricted to gray matter. The objective of the current study was to determine whether the regions of white matter fMRI activation were structurally connected to the functional network in gray matter. To do this, we used fMRI-guided tractography to evaluate whether tracts connecting regions of gray matter fMRI activation were co-localized with white matter fMRI activation. An established interhemispheric transfer task was employed to elicit activation in the corpus callosum. Diffusion tensor imaging (DTI) tractography was used to determine the existence of tracts that connected regions of gray matter fMRI activation to regions of activation in the corpus callosum. Corpus callosum activation was detected in the majority of participants. While there was individual variability in the location of corpus callosum activation, activation was commonly observed in the callosal mid-body, isthmus/splenium, or both. Despite the variability, gray matter fMRI-guided tractography identified tracts that were co-localized with corpus callosum fMRI activation in all instances. In addition, callosal activation had tracts to bilateral gray matter fMRI activation for 7/8 participants. The results confirmed that the activated regions of the corpus callosum were structurally connected to the functional network of gray matter regions involved in the task. These findings are an important step towards establishing the functional significance of white matter fMRI, and provide the foundation for future work combining white matter fMRI and DTI tractography to study brain connectivity., (Copyright 2010 Elsevier Inc. All rights reserved.)

Functional MRI (fMRI) is of limited use in areas such as the orbitofrontal and inferior temporal lobes due to the presence of local susceptibility-induced field gradients (SFGs), which result in severe image artifacts. Several techniques have been developed to reduce these artifacts, the most common being the dual-echo spiral sequences (spiral-in/out and spiral-in/in). In this study, a new multiple spiral acquisition technique was developed, in which the later spiral acquisitions are acquired asymmetrically with the peak of a spin-echo causing increased R(2)-weighting but matched R(2)'-weighting. This sequence, called asymmetric spin-echo (ASE) spiral, has demonstrated significant improvements in minimizing the signal loss and increasing the image quality as well as optimal blood-oxygen-level-dependent (BOLD)-weighting. The ASE spiral is compared to conventional spiral-out using both signal-to-noise ratio (SNR) and whole brain fMRI activation volumes from a breath-hold task acquired at 4 Tesla. The ASE dual spiral has exhibited SNR increases of up to 300% in areas where strong SFGs are present. As a result, the ASE spiral is highly efficient for recovering lost activation in areas of SFGs, as demonstrated by a 16% increase in the total number of activated voxels over the whole brain. Post spin-echo ASE spiral images have decreasing SNR due to R(2) signal losses, however the increase in R(2)-weighting leads to a higher percentage of signal changes producing ASE spiral images with equivalent contrast-to-noise ratio (CNR) for each echo. The use of this sequence allows for recovery of BOLD activation in areas of SFG without sacrificing the CNR over the whole brain., (Copyright (c) 2009 John Wiley & Sons, Ltd.)

The majority of functional magnetic resonance imaging (fMRI) studies restrict their focus to gray matter regions because this tissue is highly perfused relative to white matter. However, an increasing number of studies are reporting fMRI activation in white matter. The current study had two objectives: 1) to evaluate whether it is possible to detect white matter fMRI activation and 2) to determine whether certain MRI contrast mechanisms are more sensitive to white matter activation (i.e., BOLD contrast- versus T(2)-weighting). Data were acquired from a 4 T MRI using an asymmetric spin echo spiral sequence (ASE spiral). This technique collected three images with equal BOLD contrast weighting and increasing T(2)-weighting. An interhemispheric transfer task was used to elicit activation in the corpus callosum. White matter fMRI activation was examined for the averaged ASE spiral data and for each image separately. Callosal activation was present in all subjects as well as in the group analysis. Analyses revealed that increasing T(2) contrast improved sensitivity as measured by percent signal change. The results suggest that it is possible to detect white matter activation in fMRI and that ASE spiral showed increasing sensitivity to this activation as a function of T(2)-weighting. The findings provide further support for the investigation of white matter fMRI.

A MR microscopy experiment is developed and used to characterize fluid ingress and microstructural transformation in degradable calcium polyphosphate (CPP) bioceramics. High-resolution (49microm) maps of fluid density and spin-lattice relaxation rate were obtained as a function of time for CPP immersed in phosphate buffered saline. These results demonstrate clear differences in fluid transport rates and solid matrix microstructure in two differing CPP formulations. CPP has been proposed as a potential implantable device for the delivery of pharmaceuticals, and the magnetic resonance imaging (MRI) data are used in conjunction with previously reported bulk elution results to develop a hypothesis explaining microstructural evolution in these materials. This type of non-destructive evaluation of the structure-transport of fluids in CPP is important to improved design of these functionalized biomaterials for long-term, localized delivery of sustained levels of therapeutic agents.

This communication presents the results of T2-weighted nuclear magnetic resonance imaging (MRI) of a water saturated porous volcanic rock using a fast single point imaging technique (turboSPI). Imaging porous materials with heterogeneously distributed mineral products, and air voids, using conventional imaging methods, which introduce T2-weighting by increasing the time between the excitation and refocusing pulses, often results in high diffusive signal losses and susceptibility distortion. T2-weighted images acquired of a water saturated porous rock using turboSPI with an effective echo time of 8.1 ms (actual inter-echo time of 0.9 ms) exhibit significantly decreased diffusive attenuation, compared to analogous images obtained with an inter-echo time of 8.1 ms.

Pulsed magnetic field gradients are fundamental to spatial encoding and diffusion weighting in magnetic resonance. The ideal pulsed magnetic field gradient should have negligible rise and fall times, however, there are physical limits to how fast the magnetic field gradient may change with time. Finite gradient switching times, and transient, secondary, induced magnetic field gradients (eddy currents) alter the ideal gradient waveform and may introduce a variety of undesirable image artifacts. We have developed a new method to measure the complete magnetic field gradient waveform. The measurement employs a heavily doped test sample with short MR relaxation times (T(1), T(2), and T(2)(*)<100 micros) and a series of closely spaced broadband radiofrequency excitations, combined with single point data acquisition. This technique, a measure of evolving signal phase, directly determines the magnetic field gradient waveform experienced by the test sample. The measurement is sensitive to low level transient magnetic fields produced by eddy currents and other short and long time constant non-ideal gradient waveform behaviors. Data analysis is particularly facile permitting a very ready experimental check of gradient performance.

A novel magnetic resonance imaging (MRI) technique which resolves the separate components of the evolving vertical concentration profiles of 3-component non-colloidal suspensions is described. This method exploits the sensitivity of MRI to chemical differences between the three phases to directly image the fluid phase and one of the solid phases, with the third phase obtained by subtraction. 19F spin-echo imaging of a polytetrafluoroethylene (PTFE) oil was interlaced with 1H SPRITE imaging of low-density polyethylene (LDPE) particles. The third phase was comprised of borosilicate glass spheres, which were not visible while imaging the PTFE or LDPE phases. The method is demonstrated by performing measurements on 2-phase materials containing only the floating (LDPE) particles, with the results contrasted to the experimental behaviour of the individual phases in the full 3-phase system. All experiments were performed using nearly monodisperse particles, with initial suspension volume fractions, phi(i), of 0.1.

Three examples of thermally polarized gas NMR performed at New Mexico Resonance are presented to demonstrate its unique advantages in porous media studies. 1) In-vivo animal lung imaging by Kuethe et al., in which useful quality 3D images of rat lungs were obtained in 30 min. It is conjectured that comparable human lung images would take much less time to make, possibly by the ratio of body weights, a factor of several hundred. 2) The success of the lung imaging suggested other porous media as candidates for thermally polarized gas NMR. Caprihan and coworkers obtained excellent images from partially sintered ceramics and Vycor glass. Since then, Beyea has developed the technique of spatially resolved BET curves for ceramics and other nanoporous solids. In this way, surface area, pore size, and porosity, averaged over an image voxel, can be spatially resolved. This greatly aids in the characterization of such materials, especially with regards to spatial heterogeneities. 3) Finally, we describe Codd's propagator experiments on propane gas flowing through a packed bed of 300 microm beads. In order to increase signal-to-noise ratio, the flowing gas was pressurized to 170 kPa. Excellent quality propagators showing the discrete nature of the bead pack were obtained. This type of information is not available in comparable liquid studies because most spins will not diffuse far enough to sample the walls in the time available.

A magnetic resonance imaging method is presented for imaging of heterogeneous broad linewidth materials. This method allows for distortionless relaxation weighted imaging by obtaining multiple phase encoded k-space data points with each RF excitation pulse train. The use of this method, turbo spin echo single-point imaging-(turboSPI), leads to decreased imaging times compared to traditional constant-time imaging techniques, as well as the ability to introduce spin-spin relaxation contrast through the use of longer effective echo times. Imaging times in turboSPI are further decreased through the use of low flip angle steady-state excitation. Two-dimensional images of paramagnetic doped agarose phantoms were obtained, demonstrating the contrast and resolution characteristics of the sequence, and a method for both amplitude and phase deconvolution was demonstrated for use in high-resolution turboSPI imaging. Three-dimensional images of a partially water-saturated porous volcanic aggregate (T(2L) approximately 200 ms, Deltanu(1/2) approximately 2500 Hz) contained in a hardened white Portland cement matrix (T(2L) approximately 0.5 ms, Deltanu(1/2) approximately 2500 Hz) and a water-saturated quartz sand (T(2) approximately 300 ms, T(2)(*) approximately 800 microseconds) are shown., (Copyright 2000 Academic Press.)

The removal of water from pores in hardened cement paste smaller than 50 nm results in cracking of the cement matrix due to the tensile stresses induced by drying shrinkage. Cracks in the matrix fundamentally alter the permeability of the material, and therefore directly affect the drying behaviour. Using Single-Point Imaging (SPI), we obtain one-dimensional moisture profiles of hydrated White Portland cement cylinders as a function of drying time. The drying behaviour of White Portland cement, is distinctly different from the drying behaviour of related concrete materials containing aggregates.

New techniques for quantitative mapping of T1, T2, and T*2 are proposed, based on the single-point imaging (SPI) method, for materials with short nuclear magnetic resonance relaxation times which cannot be imaged with traditional methods. Relaxation times extracted from two-dimensional images of uniform doped agarose phantoms (T*2 approximately 60-210 microseconds) as well as hardened mortar (T*2 approximately 220 microseconds) and polymers (T*2 approximately 20-100 microseconds), using these techniques, agreed with bulk measurements. The method was then applied to a partially dried cylindrical concrete sample (T*2 approximately 115 microseconds)., (Copyright 1998 Academic Press.)

A series of magnetic resonance imaging (MRI) water density and T2* profiles in hardened concrete and mortar samples has been obtained during freezing conditions (-50 degrees C < T < 11 degrees C). The single-point ramped imaging with T1 enhancement (SPRITE) sequence is optimal for this study given the characteristic short relaxation times of water in this porous media (T2* < 200 microseconds and T1 < 3.6 ms). The frozen and evaporable water distribution was quantified through a position based study of the profile magnitude. Submillimetric resolution of proton-density and T2*-relaxation parameters as a function of temperature has been achieved.

A series of two-dimensional images of proton distribution in a hardened concrete sample has been obtained during the thawing process (from -50 degrees C up to 11 degrees C). The SPRITE sequence is optimal for this study given the characteristic short relaxation times of water in this porous media (T2* < 200 micros and T1 < 3.6 ms). The relaxation parameters of the sample were determined in order to optimize the time efficiency of the sequence, permitting a 4-scan 64 x 64 acquisition in under 3 min. The image acquisition is fast on the time scale of the temperature evolution of the specimen. The frozen water distribution is quantified through a position based study of the image contrast. A multiple point acquisition method is presented and the signal sensitivity improvement is discussed.