Cerebral blood flow (CBF) is a well-established correlate of brain function and therefore an essential parameter for studying the brain at both normal and diseased states. Arterial spin labeling (ASL) is a noninvasive fMRI technique that uses arterial water as an endogenous tracer to measure CBF. ASL provides reliable absolute quantification of CBF with higher spatial and temporal resolution than other techniques. And yet, the routine application of ASL has been somewhat limited. In this review, we start by highlighting theoretical complexities and technical challenges of ASL fMRI for basic and clinical research. While underscoring the main advantages of ASL versus other techniques such as BOLD, we also expound on inherent challenges and confounds in ASL perfusion imaging. In closing, we expound on several exciting developments in the field that we believe will make ASL reach its full potential in neuroscience research.
Metamorphosis in amphibians presents a unique problem for the developing immune
system. Because tadpoles are free-living, they need an immune system to protect against
potential pathogens. However, at metamorphosis, they acquire a variety of new adultspecific
molecules to which the tadpole immune system must become tolerant. We
hypothesized that Xenopus laevis tadpoles may avoid potentially destructive antiself
responses by largely discarding the larval immune system at metamorphosis and
acquiring a new one. By implanting triploid (3N) thymuses into diploid (2N) hosts, we
examined the influx and expansion of host T-cell precursors in the donor thymus of
normally metamorphosing and metamorphosis-inhibited frogs. We observed that donor
thymocytes are replaced by host-derived cells during metamorphosis, but inhibition of
metamorphosis does not prevent this exchange of cells. The implanted thymuses export
T cells to the spleen. This donor-derived pool of cells declines after metamorphosis in
normally developing frogs but is retained to a greater extent if metamorphosis is
inhibited. These studies confirm previous observations of a metamorphosis-associated
wave of expansion of T cells and demonstrate that it is not dependent on the relatively
high concentrations of thyroid hormones required for metamorphosis. Although some
larval T cells persist through metamorphosis, others may be destroyed or the larval
population is significantly diluted by the expanding adult population.
Thymus ontogeny; Xenopus laevis; thyroid hormones; metamorphosis
Current hypotheses describing the function of normal airway surface liquid (ASL) in lung defense are divergent. One theory predicts that normal airways regulate ASL volume by modulating the flow of isosmotic fluid across the epithelium, whereas an alternative theory predicts that ASL is normally hyposmotic. These hypotheses predict different values for the osmotic water permeability (Pf) of airway epithelia. We measured Pf of cultures of normal and cystic fibrosis (CF) airway epithelia that, like the native tissue, contain columnar cells facing the lumen and basal cells that face a basement membrane. Xz laser scanning confocal microscopy recorded changes in epithelial height and transepithelial volume flow in response to anisosmotic challenges. With luminal hyperosmotic challenges, transepithelial and apical membrane Pf are relatively high for both normal and CF airway epithelia, consistent with an isosmotic ASL. Simultaneous measurements of epithelial cell volume and transepithelial water flow revealed that airway columnar epithelial cells behave as osmometers whose volume is controlled by luminal osmolality. Basal cell volume did not change in these experiments. When the serosal side of the epithelium was challenged with hyperosmotic solutions, the basal cells shrank, whereas the lumen-facing columnar cells did not. We conclude that (a) normal and CF airway epithelia have relatively high water permeabilities, consistent with the isosmotic ASL theory, and the capacity to restore water on airway surfaces lost by evaporation, and (b) the columnar cell basolateral membrane and tight junctions limit transepithelial water flow in this tissue.
Measurements of cerebral blood flow (CBF) with arterial spin labeling (ASL) MRI are challenging primarily due to a poor signal-to-noise (SNR) ratio. Therefore, methods that improve SNR and minimize measurement errors can play a significant role for better estimations of CBF. The purpose of this work was to develop an ASL method for measurements of CBF at high magnetic field strength. In the proposed multislice ASL method, using in-plane double inversion for labeling, stationary spins are kept at equilibrium to avoid T1 relaxation effects, while blood water is labeled using a lower magnetic field gradient. Improvement for CBF measurements is demonstrated on subjects and by comparison with other multislice ASL MRI methods at 1.5 Tesla. Furthermore, echo-planar imaging (EPI) and Turbo-FLASH (TFL) at 4 T MRI are compared for mapping CBF in human brain using various postlabeling delay times. CBF maps were obtained and analyzed within region-of-interests encompassing either gray matter or white matter. Elimination of T1 dependence of stationary spins in conjunction with avoidance of magnetization transfer mismatch between labeling and control scans lead to improved CBF measurements. Although measurements of CBF in brain tissue are feasible at 4 T using either EPI or TFL, TFL reduced contaminations from an intravascular signal and susceptibility-related artifacts, providing overall more robust CBF measurements than EPI. Therefore, the proposed ASL method in combination with TFL should be used for measuring CBF of human brain at 4T.
arterial spin labeling; cerebral blood flow; high field MRI; in-plane double inversion
Dynamic susceptibility contrast (DSC) and arterial spin labeling (ASL) are both used to measure cerebral blood flow (CBF), but neither technique is ideal. Absolute DSC-CBF quantitation is challenging due to many uncertainties, including partial-volume errors and nonlinear contrast relaxivity. ASL can measure quantitative CBF in regions with rapidly arriving flow, but CBF is underestimated in regions with delayed arrival. To address both problems, we have derived a patient-specific correction factor, the ratio of ASL- and DSC-CBF, calculated only in short-arrival-time regions (as determined by the DSC-based normalized bolus arrival time [Tmax]). We have compared the combined CBF method to gold-standard xenon CT in 20 patients with cerebrovascular disease, using a range of Tmax threshold levels. Combined ASL and DSC CBF demonstrated quantitative accuracy as good as the ASL technique but with improved correlation in voxels with long Tmax. The ratio of MRI-based CBF to xenon CT CBF (coefficient of variation) was 90 ± 30% (33%) for combined ASL and DSC CBF, 43 ± 21% (47%) for DSC, and 91 ± 31% (34%) for ASL (Tmax threshold 3 sec). These findings suggest that combining ASL and DSC perfusion measurements improves quantitative CBF measurements in patients with cerebrovascular disease.
magnetic resonance imaging; perfusion; computed tomography; xenon CT; cerebral blood flow; quantitative
Arterial spin labeling (ASL) provides noninvasive measurement of tissue blood flow, but sensitivity to motion has limited its application to imaging of myocardial blood flow (MBF). While different cardiac phases can be synchronized using ECG triggering, breath holding is generally required to minimize effects of respiratory motion during ASL scanning, which may be challenging in clinical populations. Here a free-breathing myocardial ASL technique with the potential for reliable clinical application is presented, by combining ASL with a navigator-gated, ECG-triggered TrueFISP readout sequence. Dynamic myocardial perfusion signals were measured at multiple delay times that allowed simultaneous fitting of MBF and arterial transit time (ATT). With the assist of a non-rigid motion correction program, the estimated mean MBF was 1.00±0.55mL/g/min with a mean transit time of approximately 400ms. The intraclass correlation coefficient of repeated scans was 0.89 with a mean within subject coefficient of variation (wsCV) of 22%. Perfusion response during mild to moderate stress was further measured. The capability for non-invasive, free-breathing assessment of MBF using ASL may offer an alternative approach to first-pass perfusion MRI for clinical evaluation of patients with coronary artery disease.
Myocardial blood flow (MBF); Navigator-echo; Free-breathing; Non-rigid motion correction; Arterial spin labeling (ASL)
Motivations of arterial spin labeling (ASL) at ultrahigh magnetic fields include prolonged blood T1 and greater signal-to-noise ratio (SNR). However, increased B0 and B1 inhomogeneities and increased specific absorption ratio (SAR) challenge practical ASL implementations. In this study, Turbo-FLASH (Fast Low Angle Shot) based pulsed and pseudo-continuous ASL sequences were performed at 7T, by taking advantage of the relatively low SAR and short TE of Turbo-FLASH that minimizes susceptibility artifacts. Consistent with theoretical predictions, the experimental data showed that Turbo-FLASH based ASL yielded approximately 4 times SNR gain at 7T compared to 3T. High quality perfusion images were obtained with an in-plane spatial resolution of 0.85×1.7 mm2. A further functional MRI study of motor cortex activation precisely located the primary motor cortex to the precentral gyrus, with the same high spatial resolution. Finally, functional connectivity between left and right motor cortices as well as supplemental motor area were demonstrated using resting state perfusion images. Turbo-FLASH based ASL is a promising approach for perfusion imaging at 7T, which could provide novel approaches to high spatiotemporal resolution fMRI and to investigate the functional connectivity of brain networks at ultrahigh field.
Cardiovascular disease leads in overall mortality and morbidity in the United States. Cardiovascular disparities remain high among minority and underserved groups. Deaf American Sign Language (ASL) users are an underserved and understudied group that receives little attention from researchers due to language and communication barriers. A recent ASL survey in Rochester, NY, indicated greater cardiovascular risk among Deaf participants.
To investigate risk perceptions of cardiovascular disease among Deaf ASL users, linking perceptions to features of Deaf culture and communication. This information will be used to inform future strategies to promote cardiovascular health among Deaf adults.
Methods and Participants
Four focus groups were conducted in Rochester, New York, with 22 Deaf participants in ASL. Videotaped sessions were translated and transcribed by a bilingual researcher. A team of investigators coded, analyzed and identified key themes from the data.
Themes centered on five major domains: knowledge, barriers, facilitators, practices, and dissemination. The majority of themes focused on barriers and knowledge. Barriers included lack of health care information access due to language and communication challenges, financial constraints, and stress. Inconsistent knowledge emerged from many key areas of cardiovascular health.
The study outlines key themes for improving cardiovascular health knowledge and perceptions among Deaf ASL users. Findings suggest the importance of providing health educational programs and information in ASL to maximize understanding and minimize misconceptions. When caring for Deaf ASL users, providers should take extra effort to ask about cardiovascular risk factors and confirm patients’ understanding of these factors.
ASL; Deaf; Deaf culture; cardiovascular health; risk perceptions
In the airways of those with cystic fibrosis (CF), the leading pathophysiological hypothesis is that an ion channel defect results in a relative decrease in airway surface liquid (ASL) volume, producing thick and sticky mucus that facilitates the establishment and progression of early fatal lung disease. This hypothesis predicts that any successful CF airway treatment for this fundamental channel defect should increase the ASL volume, but up until now there has been no method of measuring this volume that would be compatible with in vivo monitoring. In order to accurately monitor the volume of the ASL, we have developed a new x-ray phase contrast imaging method that utilizes a highly attenuating reference grid. In this study we used this imaging method to examine the effect of a current clinical CF treatment, aerosolized hypertonic saline, on ASL depth in ex vivo normal mouse tracheas, as the first step towards non-invasive in vivo ASL imaging. The ex vivo tracheas were treated with hypertonic saline, isotonic saline or no treatment using a nebuliser integrated within a small animal ventilator circuit. Those tracheas exposed to hypertonic saline showed a transient increase in the ASL depth, which continued for nine minutes post-treatment, before returning to baseline by twelve minutes. These findings are consistent with existing measurements on epithelial cell cultures, and therefore suggest promise for the future development of in vivo testing of treatments. Our grid-based imaging technique measures the ASL depth with micron resolution, and can directly observe the effect of treatments expected to increase ASL depth, prior to any changes in overall lung health. The ability to non-invasively observe micron changes in the airway surface, particularly if achieved in an in vivo setting, may have potential in pre-clinical research designed to bring new treatments for CF and other airway diseases to clinical trials.
Arterial spin labeling (ASL) is a magnetic resonance imaging technique that provides a non-invasive and quantitative measure of cerebral blood flow (CBF). After more than a decade of active research, ASL is now emerging as a robust and reliable CBF measurement technique with increased availability and ease of use. There is a growing number of research and clinical sites using ASL for neuroscience research and clinical care. In this paper, we present an online CBF Database and Analysis Pipeline, collectively called the Cerebral Blood Flow Biomedical Informatics Research Network (CBFBIRN) that allows researchers to upload and share ASL and clinical data. In addition to serving the role as a central data repository, the CBFBIRN provides a streamlined data processing infrastructure for CBF quantification and group analysis, which has the potential to accelerate the discovery of new scientific and clinical knowledge. All capabilities and features built into the CBFBIRN are accessed online using a web browser through a secure login. In this work, we begin with a general description of the CBFBIRN system data model and its architecture, then devote the remainder of the paper to the CBFBIRN capabilities. The latter part of our work is divided into two processing modules: (1) Data Upload and CBF Quantification Module; (2) Group Analysis Module that supports three types of analysis commonly used in neuroscience research. To date, the CBFBIRN hosts CBF maps and associated clinical data from more than 1,300 individual subjects. The data have been contributed by more than 20 different research studies, investigating the effect of various conditions on CBF including Alzheimer’s, schizophrenia, bipolar disorder, depression, traumatic brain injury, HIV, caffeine usage, and methamphetamine abuse. Several example results, generated by the CBFBIRN processing modules, are presented. We conclude with the lessons learned during implementation and deployment of the CBFBIRN and our experience in promoting data sharing.
database; data sharing; arterial spin labeling; cerebral blood flow; perfusion imaging; group analysis; magnetic resonance imaging
Metamorphosis in the bryozoan Bugula neritina (Linne) includes an initial phase of rapid morphological rearrangement followed by a gradual phase of morphogenesis. We hypothesized that the first phase may be independent of de novo synthesis of proteins and, instead, involves post-translational modifications of existing proteins, providing a simple mechanism to quickly initiate metamorphosis. To test our hypothesis, we challenged B. neritina larvae with transcription and translation inhibitors. Furthermore, we employed 2D gel electrophoresis to characterize changes in the phosphoproteome and proteome during early metamorphosis. Differentially expressed proteins were identified by liquid chromatography tandem mass spectrometry and their gene expression patterns were profiled using semi-quantitative real time PCR.
When larvae were incubated with transcription and translation inhibitors, metamorphosis initiated through the first phase but did not complete. We found a significant down-regulation of 60 protein spots and the percentage of phosphoprotein spots decreased from 15% in the larval stage to12% during early metamorphosis. Two proteins--the mitochondrial processing peptidase beta subunit and severin--were abundantly expressed and phosphorylated in the larval stage, but down-regulated during metamorphosis. MPPbeta and severin were also down-regulated on the gene expression level.
The initial morphogenetic changes that led to attachment of B. neritina did not depend on de novo protein synthesis, but the subsequent gradual morphogenesis did. This is the first time that the mitochondrial processing peptidase beta subunit or severin have been shown to be down-regulated on both gene and protein expression levels during the metamorphosis of B. neritina. Future studies employing immunohistochemistry to reveal the expression locality of these two proteins during metamorphosis should provide further evidence of the involvement of these two proteins in the morphogenetic rearrangement of B. neritina.
To use arterial spin labeling (ASL) to compare cerebral blood flow (CBF) patterns in minimally conscious state (MCS) patients with those in normal controls in an observational study design.
Subjects meeting MCS criteria and normal controls were identified. A pseudocontinuous ASL sequence was performed with subjects and controls in the resting awake state. Multiple CBF values for 10 predetermined regions of interest were sampled and average CBF was calculated and compared between controls and subjects.
Ten normal controls were identified, with ages ranging from 26 to 54 years. Four subjects met the MCS criteria and received an ASL study, with one patient receiving a second study at a later date. Subjects ranged in age from 19 to 58 years and had traumatic brain injury, stroke, or hypoxic-ischemic encephalopathy. Regional CBF for controls ranged from 21.6 to 57.2 mL/100 g/min, with a pattern of relatively increased blood flow posteriorly including the posterior cingulate, parietal, and occipital cortices. CBF patterns for MCS subjects showed greater variability (from 7.7 to 33.1 mL/100 g/min), demonstrating globally decreased CBF in gray matter compared with that in normal controls, especially in the medial prefrontal and midfrontal regions. In the one subject studied longitudinally, global CBF values increased over time, which correlated with clinical improvement.
We identified globally decreased CBF and a selective reduction of CBF within the medial prefrontal and midfrontal cortical regions as well as gray matter in MCS patients. ASL may serve as an adjunctive method to assess functional reserve in patients recovering from severe brain injuries.
Deployment of new model species in the plant biology community requires the development and/or improvement of numerous genetic tools. Sequencing of the Arabidopsis thaliana genome opened up a new challenge of assigning biological function to each gene. As many genes exhibit spatiotemporal or other conditional regulation of biological processes, probing for gene function necessitates applications that can be geared toward temporal, spatial and quantitative functional analysis in vivo. The continuing quest to establish new platforms to examine plant gene function has resulted in the availability of numerous genomic and proteomic tools. Classical and more recent genome-wide experimental approaches include conventional mutagenesis, tagged DNA insertional mutagenesis, ectopic expression of transgenes, activation tagging, RNA interference and two-component transactivation systems. The utilization of these molecular tools has resulted in conclusive evidence for the existence of many genes, and expanded knowledge on gene structure and function. This review covers several molecular tools that have become increasingly useful in basic plant research. We discuss their advantages and limitations for probing cellular protein function while emphasizing the contributions made to lay the fundamental groundwork for genetic manipulation of crops using plant biotechnology.
enhancer trap; RNAi; plant transformation; transactivation; transgenic
The population increase in the over 65 age group creates a challenge and responsibility for family physicians in the continuing and comprehensive care of the aged. Family physicians have to assess the medical, psychological and social needs of the elderly and provide them with the best care available by utilizing local facilities, community resources, health care personnel, and whenever possible, the cooperation of the patient's family. Medical students, family practice trainees and other health professionals require the appropriate training. New trends in the care of the elderly and medical education geared towards this task are discussed.
Malaria continues to be an enormous global health challenge, with millions of new infections and deaths reported annually. This is partly due to the development of resistance by the malaria parasite to the majority of established anti-malarial drugs, a situation that continues to hamper attempts at controlling the disease. This has spurred intensive drug discovery endeavours geared towards identifying novel, highly active anti-malarial drugs, and the identification of quality leads from natural sources would greatly augment these efforts. The current reality is that other than compounds that have their foundation in historic natural products, there are no other compounds in drug discovery as part of lead optimization projects and preclinical development or further that have originated from a natural product start-point in recent years. This paper briefly presents both classical as well as some more modern, but underutilized, approaches that have been applied outside the field of malaria, and which could be considered in enhancing the potential of natural products to provide or inspire the development of anti-malarial lead compounds.
Intravital microscopy is an extremely powerful tool that enables imaging several biological processes in live animals. Recently, the ability to image subcellular structures in several organs combined with the development of sophisticated genetic tools has made possible extending this approach to investigate several aspects of cell biology. Here we provide a general overview of intravital microscopy with the goal of highlighting its potential and challenges. Specifically, this review is geared toward researchers that are new to intravital microscopy and focuses on practical aspects of carrying out imaging in live animals. Here we share the know-how that comes from first-hand experience, including topics such as choosing the right imaging platform and modality, surgery and stabilization techniques, anesthesia and temperature control. Moreover, we highlight some of the approaches that facilitate subcellular imaging in live animals by providing numerous examples of imaging selected organelles and the actin cytoskeleton in multiple organs.
Activists in the environmental justice movement are challenging expert-driven scientific research by taking the research process into their own hands and speaking for themselves by defining, analyzing, and prescribing solutions for the environmental health hazards confronting communities of the poor and people of color. I highlight the work of El Puente and The Watchperson Project--two community-based organizations in the Greenpoint/Williamsburg neighborhood in Brooklyn, New York, that have engaged in community-based participatory research (CBPR) to address asthma and risks from subsistence-fish diets. The CBPR process aims to engage community members as equal partners alongside scientists in problem definition, information collection, and data analysis--all geared toward locally relevant action for social change. In the first case I highlight how El Puente has organized residents to conduct a series of asthma health surveys and tapped into local knowledge of the Latino population to understand potential asthma triggers and to devise culturally relevant health interventions. In a second case I follow The Watchperson Project and their work surveying subsistence anglers and note how the community-gathered information contributed key data inputs for the U.S. Environmental Protection Agency Cumulative Exposure Project in the neighborhood. In each case I review the processes each organization used to conduct CBPR, some of their findings, and the local knowledge they gathered, all of which were crucial for understanding and addressing local environmental health issues. I conclude with some observations about the benefits and limits of CBPR for helping scientists and communities pursue environmental justice.
Arterial spin labeling (ASL) perfusion fMRI is an emerging method in clinical neuroimaging. Its non-invasiveness, absence of low frequency noise, and ability to quantify the absolute level of cerebral blood flow (CBF) make the method ideal for longitudinal designs or low frequency paradigms. Despite the usefulness in the study of cognitive dysfunctions in clinical populations, perfusion activation studies to date have been conducted for simple sensorimotor paradigms or with single-slice acquisition, mainly due to technical challenges. Using our recently developed amplitude-modulated continuous ASL (CASL) perfusion fMRI protocol, we assessed the feasibility of a higher level cognitive activation study in twelve healthy subjects. Taking advantage of the ASL noise properties, we were able to study tonic CBF changes during uninterrupted 6-min continuous performance of working memory and sustained attention tasks. For the visual sustained attention task, regional CBF increases (6-12 ml/100 g/min) were detected in the right middle frontal gyrus, the bilateral occipital gyri, and the anterior cingulate/medial frontal gyri. During the 2-back working memory task, significantly increased activations (7-11 ml/100 g/min) were found in the left inferior frontal/precentral gyri, the left inferior parietal lobule, the anterior cingulate/medial frontal gyri, and the left occipital gyrus. Locations of activated and deactivated areas largely concur with previous PET and BOLD fMRI studies utilizing similar paradigms. These results demonstrate that CASL perfusion fMRI can be successfully utilized for the investigation of the tonic CBF changes associated with high level cognitive operations. Increased applications of the method to the investigation of cognitively impaired populations are expected to follow.
Arterial spin labeling; CASL; Cerebral blood flow; 2-back task; Clinical neuroimaging
To date, functional magnetic resonance imaging (fMRI) studies of the lateral geniculate nucleus (LGN) have primarily focused on measures of the blood oxygenation level dependent (BOLD) signal. Arterial spin labeling (ASL) is an MRI method that can provide direct measures of functional cerebral blood flow (CBF) changes. Because CBF is a well-defined physiological quantity that contributes to BOLD contrast, CBF measures can be used to improve the quantitative interpretation of fMRI studies. However, due in part to the low intrinsic signal-to-noise ratio of the ASL method, measures of functional CBF changes in the LGN are challenging and have not previously been reported. In this study, we demonstrate the feasibility of using ASL fMRI to measure the CBF response of the LGN to visual stimulation on a 3 T MRI system. The use of background suppression and physiological noise reduction techniques allowed reliable detection of LGN activation in all five subjects studied. The measured percent CBF response during activation ranged from 40 to 100%, assuming no interaction between the left and right LGN.
lateral geniculate nucleus; arterial spin labeling; functional magnetic resonance imaging; background suppression; physiological noise reduction
The purpose of this study was to assess the ability of a flow-sensitive alternating inversion recovery–arterial spin labeling (FAIR-ASL) technique to track renal perfusion changes during pharmacologic and physiologic alterations in renal blood flow using microspheres as a gold standard.
Materials and Methods
Fluorescent microsphere and FAIR-ASL perfusion were compared in the cortex of the kidney for 11 swine across 4 interventional time points: (1) under baseline conditions, (2) during an acetylcholine and fluid bolus challenge to increase perfusion, (3) initially after switching to isoflurane anesthesia, and (4) after 2 hours of isoflurane anesthesia. In 10 of the 11 swine, a bag of ice was placed on the hilum of 1 kidney at the beginning of isoflurane administration to further reduce perfusion in 1 kidney.
Both ASL and microspheres tracked the expected cortical perfusion changes (P < 0.02) across the interventions, including an increase in perfusion during the acetylcholine challenge and decrease during the administration of isoflurane. Both techniques also measured lower cortical perfusion in the iced compared with the noniced kidneys (P ≤ 0.01). The ASL values were systematically lower compared with microsphere perfusion. Very good correlation (r = 0.81, P < 0.0001) was observed between the techniques, and the relationship appeared linear for perfusion values in the expected physiologic range (microsphere perfusion <550 mL/min/100 g) although ASL values saturated for perfusion >550 mL/min/100 g.
Cortical perfusion measured with ASL correlated with microspheres and reliably detected changes in renal perfusion in response to physiologic challenge.
kidney perfusion; MRI; arterial spin labeling; renal perfusion; swine; microspheres
Pseudo-Continuous Arterial Spin Labeling (pCASL) MRI is a new ASL technique that has the potential of combining advantages of Continuous-ASL and Pulsed-ASL. However, unlike CASL, the labeling process of pCASL is not strictly an adiabatic inversion and the efficiency of labeling may be subject-specific. Here three experiments were performed to study the labeling efficiency in pCASL MRI. First, the optimal labeling position was determined empirically to be approximately 84 mm below Anterior-Commissure Posterior-Commissure line in order to achieve the highest sensitivity. Second, an experimental method was developed to utilize phase-contrast velocity MRI as a normalization factor and to estimate the labeling efficiency in vivo, which was founded to be 0.86±0.06 (n=10, mean±SD). Third, we compared the labeling efficiency of pCASL MRI under normocapnic and hypercapnic (inhalation of 5% CO2) conditions, and showed that a higher flow velocity in the feeding arteries resulted in a reduction in the labeling efficiency. In summary, our results suggest that labeling efficiency is a critical parameter in pCASL MRI not only in terms of achieving highest sensitivity but also in quantification of absolute CBF in ml/min/100g. We propose that the labeling efficiency should be estimated using phase-contrast velocity MRI on a subject-specific basis.
ASL MRI; cerebral blood flow; pCASL; Labeling Efficiency; Perfusion; Hypercapnia
To investigate arterial spin labeling (ASL) methods for improved brain perfusion mapping. Previously, Pseudo-continuous arterial spin labeling (pCASL) was developed to overcome limitations inherent with conventional continuous arterial spin labeling (CASL), but the control scan (null pulse) in the original method for pCASL perturbs the equilibrium magnetization, diminishing the ASL signal. Here, a new modification of pCASL, termed mpCASL is reported, in which the perturbation caused by the null pulse is reduced and perfusion mapping improved.
Materials and Methods
Improvements with mpCASL are demonstrated using numerical simulations and experiments. ASL signal intensity as well as contrast and reproducibility of in-vivo brain perfusion images were measured in four volunteers who had MRI scans at 4 Tesla and the data compared across the labeling methods.
Perfusion maps with mpCASL showed, on average, higher ASL signal intensity and higher image contrast than those from CASL or pCASL. Furthermore, mpCASL yielded better reproducibility in repeat scans than the other methods.
The experimental results are consistent with the hypothesis that the new null pulse of mpCASL leads to improved brain perfusion images.
MR Perfusion imaging; Arterial spin labeling; Alzheimer’s disease
Numerous publications demonstrate the importance of community-based participatory research (CBPR) in community health research, but few target the Deaf community. The Deaf community is understudied and underrepresented in health research despite suspected health disparities and communication barriers.
The goal of this paper is to share the lessons learned from the implementation of CBPR in an understudied community of Deaf American Sign Language (ASL) users in the greater Rochester, New York, area.
We review the process of CBPR in a Deaf ASL community and identify the lessons learned.
Key CBPR lessons include the importance of engaging and educating the community about research, ensuring that research benefits the community, using peer-based recruitment strategies, and sustaining community partnerships. These lessons informed subsequent research activities.
This report focuses on the use of CBPR principles in a Deaf ASL population; lessons learned can be applied to research with other challenging-to-reach populations.
Community-based participatory research; health disparities; vulnerable populations; academic medical centers; health care facilities manpower and services; Deaf American Sign Language users
Multimodal imaging improves the accuracy of the localization and the quantification of brain activation when measuring different manifestations of the hemodynamic response associated with cerebral activity. In this study, we incorporated cerebral blood flow (CBF) changes measured with arterial spin labeling (ASL), Diffuse Optical Tomography (DOT) and blood oxygen level-dependent (BOLD) recordings to reconstruct changes in oxy- (ΔHbO2) and deoxyhemoglobin (ΔHbR). Using the Grubb relation between relative changes in CBF and cerebral blood volume (CBV), we incorporated the ASL measurement as a prior to the total hemoglobin concentration change (ΔHbT). We applied this ASL fusion model to both synthetic data and experimental multimodal recordings during a 2-sec finger-tapping task. Our results show that the new approach is very powerful in estimating ΔHbO2 and ΔHbR with high spatial and quantitative accuracy. Moreover, our approach allows the computation of baseline total hemoglobin concentration (HbT0) as well as of the BOLD calibration factor M on a single subject basis. We obtained an average HbT0 of 71 μM, an average M value of 0.18 and an average increase of 13 % in cerebral metabolic rate of oxygen (CMRO2), all of which are in agreement with values previously reported in the literature. Our method yields an independent measurement of M, which provides an alternative measurement to validate the hypercapnic calibration of the BOLD signal.
fNIRS; fMRI; ASL; CMRO2; BOLD calibration; multimodal imaging
The ability to assess brain tumor perfusion and abnormalities in the vascular structure in vivo could provide significant benefits in terms of lesion diagnosis and assessment of treatment response. Arterial spin labeling (ASL) has emerged as an increasingly viable methodology for non-invasive assessment of perfusion. Although kinetic models have been developed to describe perfusion in healthy tissue, the dynamic behaviour of the ASL signal in the brain tumor environment has not been extensively studied. We show here that dynamic ASL data acquired in brain tumors displays an increased level of ‘biphasic’ behaviour, compared to that seen in healthy tissue. A new two-stage model is presented which more accurately describes this behaviour, and provides measurements of perfusion, pre-capillary blood volume fraction and transit time, and capillary bolus arrival time. These biomarkers offer a novel contrast in the tumor and surrounding tissue, and provide a means for measuring tumor perfusion and vascular structural abnormalities in a fully non-invasive manner.