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The assumption of linear time-invariance (LTI) in the human primary somatosensory cortex (SI) is assessed for fMRI signals generated by variable-duration vibrotactile stimuli. Predictions based on time-shifted summation (TSS) of responses to 2 s stimuli overestimate observed BOLD signal amplitudes in response to longer-duration stimuli, in agreement with previous findings in other primary sensory cortices. To interpret these results, we undertook an alternative approach for LTI assessment by characterizing BOLD signals using two biophysical models. The first model assumes that the input stimulus envelope is proportional to neural activity. The second assumes that neural activity exhibits both transient and steady-state components, consistent with extensive electrophysiological data, and fits the experimental data better. Although nonlinearity remains evident for short stimulus durations, the latter model shows that the TSS procedure to assess LTI overestimates the BOLD signal because the temporal characteristics of neural activity have not been considered adequately. Further research to investigate the BOLD response to time-varying neural activity is required.

Continuous wave near-infrared spectroscopy (NIRS) measurements of cardiac correlated changes in attenuation in the adult human head were computed using a Fourier analysis technique that eliminates the positive error bias associated with the magnitude of the Fourier coefficient. These attenuation changes were used to determine wavelength dependence of differential pathlength, DP(lambda), at four stages during progressive hypoxia (21, 17, 13 and 9% FIO2) in normal volunteers. The effects of incorporating DP(lambda) into NIRS algorithms to compute relative concentration changes and absolute concentration of oxyhaemoglobin and deoxyhaemoglobin are discussed. Because variations in DP(lambda) are restricted to wavelengths below 780 nm, absolute concentration calculations are influenced by hypoxia-induced changes while relative concentrations are unaffected. However, even accounting for changes in DP(lambda) did not allow computation of physiologically reasonable absolute concentrations of the haemoglobin species.

Habitual long term physical activity is known to have beneficial cognitive, structural, and neuro-protective brain effects, but to date there is limited knowledge on whether a single session of exercise can alter the brain’s functional connectivity, as assessed by resting-state functional magnetic resonance imaging (rs-fMRI). The primary objective of this study was to characterize potential session effects in resting-state networks (RSNs). We examined the acute effects of exercise on the functional connectivity of young healthy adults (N = 15) by collecting rs-fMRI before and after 20 min of moderate intensity aerobic exercise and compared this with a no-exercise control group (N = 15). Data were analyzed using independent component analysis, denoising and dual regression procedures. Regions of interest-based group session effect statistics were calculated in RSNs of interest using voxel-wise permutation testing and Cohen’s D effect size. Group analysis in the exercising group data set revealed a session effect in sub-regions of three sensorimotor related areas: the pre and/or postcentral gyri, secondary somatosensory area and thalamus, characterized by increased co-activation after exercise (corrected p < 0.05). Cohen’s D analysis also showed a significant effect of session in these three RSNs (p< 0.05), corroborating the voxel-wise findings. Analyses of the no-exercise dataset produced no significant results, thereby providing support for the exercise findings and establishing the inherent test–retest reliability of the analysis pipeline on the RSNs of interest. This study establishes the feasibility of rs-fMRI to localize brain regions that are associated with acute exercise, as well as an analysis consideration to improve sensitivity to a session effect.

The rising prevalence of type 2 diabetes (T2DM) and hypertension in older adults, and the deleterious effect of these conditions on cerebrovascular and brain health, is creating a growing discrepancy between the "typical" cognitive aging trajectory and a "healthy" cognitive aging trajectory. These changing health demographics make T2DM and hypertension important topics of study in their own right, and warrant attention from the perspective of cognitive aging neuroimaging research. Specifically, interpretation of individual or group differences in blood oxygenation level dependent magnetic resonance imaging (BOLD MRI) or positron emission tomography (PET H2O15) signals as reflective of differences in neural activation underlying a cognitive operation of interest requires assumptions of intact vascular health amongst the study participants. Without adequate screening, inclusion of individuals with T2DM or hypertension in "healthy" samples may introduce unwanted variability and bias to brain and/or cognitive measures, and increase potential for error. We conducted a systematic review of the cognitive aging neuroimaging literature to document the extent to which researchers account for these conditions. Of the 232 studies selected for review, few explicitly excluded individuals with T2DM (9%) or hypertension (13%). A large portion had exclusion criteria that made it difficult to determine whether T2DM or hypertension were excluded (44% and 37%), and many did not mention any selection criteria related to T2DM or hypertension (34% and 22%). Of all the surveyed studies, only 29% acknowledged or addressed the potential influence of intersubject vascular variability on the measured BOLD or PET signals. To reinforce the notion that individuals with T2DM and hypertension should not be overlooked as a potential source of bias, we also provide an overview of metabolic and vascular changes associated with T2DM and hypertension, as they relate to cerebrovascular and brain health.

To determine functional and structural neuroimaging correlates of cognitive dysfunction associated with cannabis use in multiple sclerosis (MS).In a cross-sectional study, 20 subjects with MS who smoked cannabis and 19 noncannabis users with MS, matched on demographic and neurologic variables, underwent fMRI while completing a test of working memory, the N-Back. Resting-state fMRI and structural MRI data (lesion and normal-appearing brain tissue volumes, diffusion tensor imaging metrics) were also collected. Neuropsychological data pertaining to verbal (Selective Reminding Test Revised) and visual (10/36 Spatial Recall Test) memory, information processing speed (Paced Auditory Serial Addition Test [2- and 3-second versions] and Symbol Digit Modalities Test), and attention (Word List Generation) were obtained.The cannabis group performed more poorly on the more demanding of the Paced Auditory Serial Addition Test tasks (i.e., 2-second version) (p0.02) and the 10/36 Spatial Recall Test (p0.03). Cannabis users had more diffuse cerebral activation across all N-Back trials and made more errors on the 2-Back task (p0.006), during which they displayed increased activation relative to nonusers in parietal (p0.007) and anterior cingulate (p0.001) regions implicated in working memory. No group differences in resting-state networks or structural MRI variables were found.Patients with MS who smoke cannabis are more cognitively impaired than nonusers. Cannabis further compromises cerebral compensatory mechanisms, already faulty in MS. These imaging data boost the construct validity of the neuropsychological findings and act as a cautionary note to cannabis users and prescribers.

Objective Type 2 diabetes mellitus is characterized by metabolic dysregulation in the form of hyperglycemia and insulin resistance and can have a profound impact on brain structure and vasculature. The primary aim of this study was to identify brain regions where the combined effects of type 2 diabetes and hypertension on brain health exceed those of hypertension alone. A secondary objective was to test whether vascular impairment and structural brain measures in this population are associated with cognitive function. Research design and methods We enrolled 18 diabetic participants with hypertension (HTN + T2DM, 7 women, 71.8 ± 5.6 years) and 22 participants with hypertension only (HTN, 12 women, 73.4 ± 6.2 years). Cerebrovascular reactivity (CVR) was assessed using blood oxygenation level dependent (BOLD) MRI during successive breath holds. Gray matter structure was evaluated using cortical thickness (CThk) measures estimated from T1-weighted images. Analyses of cognitive and blood data were also performed. Results Compared to HTN, HTN + T2DM had decreased CVR and CThk in a spatially overlapping region of the right occipital lobe (P 0.05), CThk in the right lingual gyrus ROI and regions resulting from a vertex-wise analysis (including posterior cingulate, precuneus, superior and middle frontal, and middle and inferior temporal regions (P, Highlights • CThk and CVR decrease in the presence of T2DM and HTN vs. HTN alone. • Combined effects of T2DM and HTN are prominent in the right occipital areas. • CVR impairment in HTN + T2DM extends to bilateral occipito-parietal areas. • Executive function correlates with CThk but not CVR in this cohort.

PURPOSE: Despite the generally accepted view that aerobic exercise can have positive effects on brain health, few studies have measured brain responses to exercise over a short time span. The purpose of this study was to examine the impact within one hour of a single bout of exercise on brain perfusion and neuronal activation. METHODS: Healthy adults (n = 16; age range: 20-35 yrs) were scanned using Magnetic Resonance Imaging (MRI) before and after 20 minutes of exercise at 70% of their age-predicted maximal heart rate. Pseudo-continuous arterial spin labeling (pcASL) was used to measure absolute cerebral blood flow (CBF) prior to exercise (pre) and at 10 min (post-10) and 40 min (post-40) post-exercise. Blood oxygenation level dependent (BOLD) functional MRI (fMRI) was performed pre and post-exercise to characterize activation differences related to a go/no-go reaction time task. RESULTS: Compared to pre-exercise levels, grey matter CBF was 11% (±9%) lower at post-10 (P

Purpose Physical activity is associated with positive effects on the brain but there is a paucity of clinical neuroimaging data in patients with coronary artery disease (CAD), a cardiovascular condition associated with grey matter loss. The purpose of this study was to determine which brain regions are impacted by cardiopulmonary fitness and with the change in fitness after 6 months of exercise-based cardiac rehabilitation. Methods CAD patients underwent magnetic resonance imaging at baseline, and peak volume of oxygen uptake during exercise testing (VO2Peak) was measured at baseline and after 6 months of training. T1-weighted structural images were used to perform grey matter (GM) voxel-based morphometry (VBM). Pseudo-continuous arterial spin labeling (pcASL) was used to produce cerebral blood flow (CBF) images. VBM and CBF data were tested voxel-wise using VO2Peak and age as explanatory variables. Results In 30 men with CAD (mean age 65±7 years), VBM and CBF identified 7 and 5 respective regions positively associated with baseline VO2Peak. These included the pre- and post-central, paracingulate, caudate, hippocampal regions and converging findings in the putamen. VO2Peak increased by 20% at follow-up in 29 patients (t = 9.6, df = 28, p

Bolus dispersion in DSC-MRI can lead to errors in cerebral blood flow (CBF) estimation by up to 70% when using singular value decomposition analysis. However, it might be possible to correct for dispersion using two alternative methods: the vascular model (VM) and control point interpolation (CPI). Additionally, these approaches potentially provide a means to quantify the microvascular residue function.VM and CPI were extended to correct for dispersion by means of a vascular transport function. Simulations were performed at multiple dispersion levels and an in vivo analysis was performed on a healthy subject and two patients with carotid atherosclerotic disease.Simulations showed that methods that could not address dispersion tended to underestimate CBF (ratio in CBF estimation, CBFratio = 0.57-0.77) in the presence of dispersion; whereas modified CPI showed the best performance at low-to-medium dispersion; CBFratio = 0.99 and 0.81, respectively. The in vivo data showed trends in CBF estimation and residue function that were consistent with the predictions from simulations.In patients with atherosclerotic disease the estimated residue function showed considerable differences in the ipsilateral hemisphere. These differences could partly be attributed to dispersive effects arising from the stenosis when dispersion corrected CPI was used. It is thus beneficial to correct for dispersion in perfusion analysis using this method.

An exponential residue function is commonly used in numerical simulations to assess the accuracy of perfusion quantification using dynamic susceptibility contrast (DSC) MRI. Although this might be a reasonable assumption for normal tissue, microvascular hemodynamics are likely to be significantly altered in pathology. Thus the exponential function may no longer be appropriate and the estimated accuracy of DSC-MRI quantification might be inappropriate. The purpose of this study was to characterize in vivo residue function variations in normal and infarcted tissue in a chronic atherosclerotic disease cohort, and to find the most appropriate model for use in DSC simulations.Residue functions were measured in vivo in patients with atherosclerotic disease using a nonparametric Control Point Interpolation method, which has been shown to provide a robust characterization of the shape of the residue function. The observed residue functions were approximated with five commonly used analytical expressions: exponential, bi-exponential, Lorentzian, and Fermi functions, and a previously proposed Vascular Model.The lowest error was found with the bi-exponential function approximations to the in vivo residue functions from both normal and infarcted tissue.A bi-exponential model should therefore be used in future numerical simulations of DSC-MRI instead of the exponential function.

Diagnostic imaging is an invaluable aspect of clinical stroke medicine, providing the location, volume, and the nature of the stroke lesion. Anatomical stroke imaging typically has been done with computed tomography (CT), but ever increasingly is supplanted by the superb soft tissue contrast provided by magnetic resonance imaging (MRI). It is more cumbersome to obtain MRI in acute stroke patients; so at many centers, CT remains the initial screening test, with or without contrast administration (CT angiography, CT perfusion). This rapidly differentiates ischemic from hemorrhagic stroke and can then guide acute management, for example, with thrombolytics. The versatility of MRI methods, however, also enables much more detailed biophysical information to be obtained about stroke physiology, above and beyond lesion structure. For example, just after stroke onset, diffusion-weighted MRI (DWI) and perfusion-weighted MRI (PWI) provide information about diffusion of water molecules and microvascular blood flow within brain tissue, respectively. The DWI and PWI methods help to evaluate the ischemic zone surrounding infarcted tissue that is potentially salvageable by recanalization therapies. Magnetic resonance angiography (MRA) approaches are also available to characterize larger-scale vasculature. In the post-acute and chronic phases, functional MRI (fMRI) offers the ability to detect alterations in brain activation patterns post-stroke, either associated with a particular behavioral task or during the resting state. Lastly, it is also possible now to image blood flow in the brain noninvasively using arterial spin labeling (ASL) MRI. In this chapter, we provide a biophysical understanding of these and other basic MRI methods and discuss their application to stroke recovery.

The global burden of stroke continues to grow. Although stroke prevention strategies (e.g., medications, diet, and exercise) can contribute to risk reduction, options for acute interventions (e.g., thrombolytic therapy for ischemic stroke) are limited to the minority of patients. The remaining patients are often left with profound neurological disabilities that substantially impact quality of life, economic productivity, and increase caregiver burden. In the last decade, however, the future outlook for such patients has been tempered by movement toward the view that the brain is capable of reorganizing after injury. Many now view brain recovery after stroke as an area of scientific research with large potential for therapeutic advances, far into the future (Broderick and William, 2004). As a probe of brain anatomy, function and physiology, magnetic resonance imaging (MRI) is a non-invasive and highly versatile modality that promises to play a particularly important role in such research. Here we provide a basic review of MRI physical principles and applications for assessing stroke, looking toward the future role MRI may play in improving stroke rehabilitation methods and stroke recovery.

Executive dysfunction is common during and between mood episodes in bipolar disorder (BD), causing social and functional impairment. This study investigated the effect of acute exercise on adolescents with BD and healthy control subjects (HC) to test for positive or negative consequences on neural response during an executive task. Fifty adolescents (mean age 16.54±1.47 years, 56% female, 30 with BD) completed an attention and response inhibition task before and after 20 min of recumbent cycling at ~70% of age-predicted maximum heart rate. 3 T functional magnetic resonance imaging data were analyzed in a whole brain voxel-wise analysis and as regions of interest (ROI), examining Go and NoGo response events. In the whole brain analysis of Go trials, exercise had larger effect in BD vs HC throughout ventral prefrontal cortex, amygdala and hippocampus; the profile of these effects was of greater disengagement after exercise. Pre-exercise ROI analysis confirmed this 'deficit in deactivation' for BDs in rostral ACC and found an activation deficit on NoGo errors in accumbens. Pre-exercise accumbens NoGo error activity correlated with depression symptoms and Go activity with mania symptoms; no correlations were present after exercise. Performance was matched to controls and results survived a series of covariate analyses. This study provides evidence that acute aerobic exercise transiently changes neural response during an executive task among adolescents with BD, and that pre-exercise relationships between symptoms and neural response are absent after exercise. Acute aerobic exercise constitutes a biological probe that may provide insights regarding pathophysiology and treatment of BD.

White matter hyperintensities (WMH) are associated with aging and are prevalent in various brain pathologies. The purpose of the current study was to characterize WMH perfusion in age-matched elderly controls (ECs) and patients with Alzheimer's disease (ADs).Fifty ECs (23 men) and 61 ADs (33 men) underwent magnetic resonance imaging (MRI), 99mTc-ECD single-photon emission computed tomography (SPECT) and cognitive testing. Brain tissue type was classified on T1 weighted images, and WMH were identified on interleaved proton density/T2 weighted images. Co-registered MR images were used to characterize SPECT perfusion patterns.WMH perfusion was lower than normal appearing white matter (NAWM) perfusion (P0.001) in both EC and AD groups. There was no WMH perfusion difference between groups when considering the mean perfusion from all WMH voxels (P0.43). However, locations that were likely to be considered WMH tended to have lower perfusion in ADs compared with ECs. Perfusion gradients along watershed white matter regions were significantly different between EC and AD groups (P0.05). A relationship was found between the volume of a WMH lesion and its mean perfusion (P0.001) in both ECs and ADs.Global WMH were hypoperfused compared with NAWM to the same degree in EC and AD participants, which suggests a common WMH etiology between groups. However, white matter locations that were likely to contain WMH tended to be hypoperfused in ADs compared with healthy aging. This finding is suggestive of AD-specific pathology that reduces the perfusion at anatomic locations susceptible to the formation of WMH through either the neurodegenerative process or AD-related vasculopathy or both.

The goal of this study was to determine whether a 3-T magnetic resonance imaging (MRI) protocol combining carotid atherosclerotic plaque and brain imaging can identify features of high-risk acutely symptomatic plaque that correlate with brain injury.It has previously been demonstrated that, in asymptomatic patients, MRI can identify features of carotid plaque that are associated with stroke, such as the presence of a large lipid core. We hypothesized that the early phase (7 days) after a cerebrovascular event, when risk of recurrence is highest, may be associated with particular plaque characteristics that associate with cerebral injury.Eighty-one patients (41 presenting acutely with transient ischemic attack [TIA] or minor stroke and 40 asymptomatic controls) underwent multicontrast carotid artery MRI on 2 separate occasions, each accompanied by diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) imaging of the brain.Complex (American Heart Association [AHA] type VI) plaques were seen in 22 of 41 patients (54%) in the symptomatic group versus 8 of 40 (20%) in the asymptomatic group (p0.05). They were caused by intraplaque hemorrhage (34% vs. 18%; p = 0.08), surface rupture (24% vs. 5%; p = 0.03), or luminal thrombus (7% vs. 0%; p = 0.24). Noticeably, 17 of 30 (57%) cases of AHA type VI plaque were in vessels with70% stenosis. At follow-up scanning (6 weeks later), only 2 cases of symptomatic AHA type VI plaque showed evidence of full healing. The presence of fibrous cap rupture was associated with higher DWI brain injury at presentation and higher total cerebral FLAIR signal at follow-up (p0.05).Early carotid wall MRI in patients experiencing minor stroke or TIA showed a higher proportion of "complex" plaques compared with asymptomatic controls; a majority were in arteries of70% stenosis. Fibrous cap rupture was associated with increases in DWI and FLAIR lesions in the brain. Combined carotid plaque and brain MRI may aid risk stratification and treatment selection in acute stroke and TIA.

In the rapidly advancing world of biomedical imaging and engineering, magnetic resonance imaging (MRI) has become an indispensable technique to visualize normal and diseased anatomy non-invasively in the human body. The 2003 Nobel prize in Physiology and Medicine to biophysicists Lauterbur and Mansfield is a testament to the significant health care advances that have followed from the early development of MRI technology. In the past three decades, MRI technology has not only matured, but has continued to diversify to encompass new applications in science and medicine. The focus of this chapter is one such application, that involves use of optoelectronic devices to measure electrical biosignals during concurrent mapping of brain activity with a technique called functional MRI (fMRI). Since the development of early MRI systems, there has been an ongoing need to develop ancillary devices adjacent to or within the magnet bore. For example, clinical MRI systems are now equipped with sensors to measure heart rate, respiratory rate, and electrocardiograph signals that provide essential summaries of the physiological status of the patient during scanning. These and other devices (e.g. wheelchairs, incubators, power injectors to deliver drugs and contrast agents, and interventional devices such as catheters) cover a wide range of functions and electromechanical complexity. However, they are all carefully designed with common consideration of several critical factors. The MRI system uses three electromagnetic fields to produce an image. First, radio-frequency (RF) coils are used to transmit and receive RF fields to and from the patient, at a frequency of approximately 100 MHz. Second, a very strong, static, homogeneous main magnetic field is required primarily for signal-to-noise ratio (SNR) considerations. This field typically has a strength of 1.5 or 3.0 Tesla, or approximately 50 000 – 100 000 times the strength of the Earth’s magnetic field, with spatial uniformity to approximately less than 1 part per million over a 20 cm diameter spherical volume. Third, time-varying magnetic gradient fields are produced along orthogonal directions by gradient coils to encode MRI signals spatially, with amplitudes of approximately 10 mT/m and slew rates of approximately 100 T/m/s.

Background and Purpose— Carotid endarterectomy (CEA) has become a routine procedure to treat symptomatic carotid artery disease and reduce the risk of recurrent cerebral ischemic events. The purpose of this study was to use an arterial spin labeling dynamic magnetic resonance angiography technique to characterize intracranial hemodynamics before and after CEA. Methods— Thirty-seven carotid artery disease patients participated in this study, of whom 24 underwent magnetic resonance imaging before and after CEA. Seventeen control subjects spanning 5 decades underwent magnetic resonance imaging to assess age-related changes. Hemodynamic metrics (that is, relative time to peak and amplitude) were calculated with a γ-variate model. Linear regression was used to relate carotid artery disease burden to downstream hemodynamics in the circle of Willis. Results— Relative time to peak increased with age in controls ( P P P P Conclusions— This noninvasive, arterial spin labeling–based method produced time-resolved images that were used to characterize intracranial arterial flow associated with aging, extracranial carotid artery disease, and CEA. Results demonstrate that the technique has the sensitivity to detect hemodynamic changes after CEA.

Increasing age and carrying an APOE e4 allele are well established risk factors for Alzheimer's disease (AD). The earlier age of onset of AD observed in e4-carriers may reflect an accelerated aging process. We recently reported that APOE genotype modulates brain function decades before the appearance of any cognitive or clinical symptoms. Here we test the hypothesis that APOE influences brain aging by comparing healthy e4-carriers and non-carriers, using the same imaging protocol in distinct groups of younger and older healthy volunteers. A cross-sectional factorial design was used to examine the effects of age and APOE genotype, and their interaction, on fMRI activation during an encoding memory task. The younger (N=36; age range 20-35; 18 e4-carriers) and older (35 middle-age/elderly; age range 50-78 years; 15 e4-carriers) healthy volunteers taking part in the study were cognitively normal. We found a significant interaction between age and e4-status in the hippocampi, frontal pole, subcortical nuclei, middle temporal gyri and cerebellum, such that aging was associated with decreased activity in e4-carriers and increased activity in non-carriers. Reduced cerebral blood flow was found in the older e4-carriers relative to older non-carriers despite preserved grey matter volume. Overactivity of brain function in young e4-carriers is disproportionately reduced with advancing age even before the onset of measurable memory impairment. The APOE genotype determines age-related changes in brain function that may reflect the increased vulnerability of e4-carriers to late-life pathology or cognitive decline.

Arterial spin labeling (ASL) provides a noninvasive method to measure brain perfusion and is becoming an increasingly viable alternative to more invasive MR methods due to improvements in acquisition, such as the use of a three-dimensional GRASE readout. A potential source of error in ASL measurements is signal arising from intravascular blood that is destined for more distal tissue. This is typically suppressed using diffusion gradients in many ASL sequences. However, several problems exist with this approach, such as the choice of cutoff velocity and gradient direction and incompatibility with certain readout modules. An alternative approach is to explicitly model the intravascular signal. This study exploits this approach by using multi-inversion time ASL data with a recently developed model-fitting method. The method employed permits the intravascular contribution to be discarded in voxels where there is no support in the data for its inclusion, thereby addressing the issue of overfitting. It is shown by comparing data with and without flow suppression, and by comparing the intravascular contribution in GRASE ASL data to MR angiographic images, that the model-fitting approach can provide a viable alternative to flow suppression in ASL where suppression is either not feasible or not desirable. Magn Reson Med 63:1357–1365, 2010. © 2010 Wiley-Liss, Inc.

A functional magnetic resonance imaging (fMRI)-compatible fiber-optic bend sensor was investigated to assess whether the device could be used effectively to monitor opening and closing of the jaw during an fMRI experiment at 3 T. In contrast to surface electromyography, a bend sensor fixed to the chin of the participant is fast and easy to use and is not affected by strong electromagnetic fields. Bend sensor recordings are characterized by high validity (compared with concurrent video recordings of mouth opening) and high reliability (comparing two independent measurements). The results of this study indicate that a bend sensor is able to record the opening and closing of the jaw associated with different overt speech conditions (producing the utterances /a/, /pa/, /pataka/) and the opening of the mouth without speech production. Data post-processing such as filtering was not necessary. There are several potential applications for bend sensor recordings of speech-related jaw movements. First, bend sensor recordings are a valuable tool to assess behavioral performance, such as response latencies, accuracies, and completion times, which is particularly important in children, seniors, or patients with various neurological or psychiatric conditions. Second, the timing information provided by bend sensor data may improve the predicted hemodynamic response that is used for fMRI analysis based on the general linear model (GLM). Third, bend sensor recordings may be included in GLM analyses not for statistical contrast purposes, but as a covariate of no interest, accounting for part of the data variance to model fMRI artifacts due to motion outside the field of view.

The purpose of this study was to establish a normal range for the arterial arrival time (AAT) in whole-brain pulsed arterial spin labeling (PASL) cerebral perfusion MRI. Healthy volunteers (N = 36, range: 20 to 35 years) provided informed consent to participate in this study. AAT was assessed in multiple brain regions, using three-dimensional gradient and spin echo (GRASE) pulsed arterial spin labeling at 3.0 T, and found to be 641 +/- 95, 804 +/- 91, 802 +/- 126, and 935 +/- 108 ms in the temporal, parietal, frontal, and occipital lobes, respectively. Mean gray matter AAT was found to be 694 +/- 89 ms for females (N = 15), which was significantly shorter than for men, 814 +/- 192 ms (N = 21; P0.0003), and significant after correcting for brain volume (P0.001). Significant AAT sex differences were also found using voxelwise permutation testing. An atlas of AAT values across the healthy brain is presented here and may be useful for future experiments that aim to quantify cerebral blood flow from ASL data, as well as for clinical comparisons where disease pathology may lead to altered AAT. Pulsed arterial spin labeling signals were simulated using an identical sampling scheme as the empiric study and revealed AAT can be estimated robustly when simulated arrival times are well beyond the normal range.

Our purpose was to use multiple inflow pulsed ASL to investigate whether hemodynamic AAT information is sensitive to hemispheric asymmetry in acute ischemia. The cohorts included 15 patients with acute minor stroke or TIA and 15 age-matched controls. Patients were scanned by using a stroke MR imaging protocol at a median time of 74 hours. DWI lesion volumes were small and functional impairment was low; however, perfusion abnormalities were evident. Prolonged AAT values were more likely to reside in the affected hemisphere (significant when compared with controls, P < .048). An advantage of this ASL technique is the ability to use AAT information in addition to CBF to characterize ischemia.

References 1. Health Care in Canada 2003, Canadian Institute for Health Information 2. Bekelman JE, Li Y, Gross CP, JAMA, vol. 289 no. 4, 454-65 3. Personal Communication with Senior Scientist at Sunnybrook Hospital 4. Ferber, D. The Scientist, Feb 5 2002, 5. Williams-Jones, B. Health Law Journal, vol. 10, 121-144 (2002) 6. Hollon T, Nature June vol. 6 no. 6, 610 (2000) 7. European Patent number: EP 0705902 8. Williams-Jones, B. PHD Thesis UBC, July 2002, 104-105.

Background. Functional magnetic resonance imaging (fMRI) appears to be useful for investigating motor recovery after stroke. Some of the potential confounders of brain activation studies, however, could be mitigated through complementary physiological monitoring. Objective. To investigate a sensorimotor fMRI battery that included simultaneous measurement of electrodermal activity in subjects with hemiparetic stroke to provide a measure related to the sense of effort during motor performance. Methods. Bilateral hand and ankle tasks were performed by 6 patients with stroke (2 subacute, 4 chronic) during imaging with blood oxygen level-dependent (BOLD) fMRI using an event-related design. BOLD percent changes, peak activation, and laterality index values were calculated in the sensorimotor cortex. Electrodermal recordings were made concurrently and used as a regressor. Results. Sensorimotor BOLD time series and percent change values provided evidence of an intact motor network in each of these well-recovered patients. During tasks involving the hemiparetic limb, electrodermal activity changes were variable in amplitude, and electrodermal activity time-series data showed significant correlations with fMRI in 3 of 6 patients. No such correlations were observed for control tasks involving the unaffected lower limb. Conclusions. Electrodermal activity activation maps implicated the contralesional over the ipsilesional hemisphere, supporting the notion that stroke patients may require higher order motor processing to perform simple tasks. Electrodermal activity recordings may be useful as a physiological marker of differences in effort required during movements of a subject's hemiparetic compared with the unaffected limb during fMRI studies.

Although multiple regions of the cerebral cortex have been implicated in swallowing, the functional contributions of each brain area remain unclear. The present study sought to clarify the roles of these cortical foci in swallowing by comparing brain activation associated with voluntary saliva swallowing and voluntary tongue elevation. Fourteen healthy right-handed subjects were examined with single-event–related functional magnetic resonance imaging (fMRI) while laryngeal movements associated with swallowing and tongue movement were simultaneously recorded. Both swallowing and tongue elevation activated 1) the left lateral pericentral and anterior parietal cortex, and 2) the anterior cingulate cortex (ACC) and adjacent supplementary motor area (SMA), suggesting that these brain regions mediate processes shared by swallowing and tongue movement. Tongue elevation activated a larger total volume of cortex than swallowing, with significantly greater activation within the ACC, SMA, right precentral and postcentral gyri, premotor cortex, right putamen, and thalamus. Although a contrast analysis failed to identify activation foci specific to swallowing, superimposed activation maps suggested that the most lateral extent of the left pericentral and anterior parietal cortex, rostral ACC, precuneus, and right parietal operculum/insula were preferentially activated by swallowing. This finding suggests that these brain areas may mediate processes specific to swallowing. Approximately 60% of the subjects showed a strong functional lateralization of the postcentral gyrus toward the left hemisphere for swallowing, whereas 40% showed a similar activation bias for the tongue elevation task. This finding supports the view that the oral sensorimotor cortices within the left and right hemispheres are functionally nonequivalent.

Compared to motor studies of the upper limb, few experiments have sought a relationship between blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) sensorimotor signals and the resulting lower limb output. In Experiment 1, using an fMRI simulator system, we determined the optimized experimental protocol based on two design types and four behavioral movement types during ankle dorsiflexion. Experiment 2 involved testing the BOLD sensitivity at 1.5 T during ankle movements. Subjects performed large- and small-amplitude dorsiflexion movement types using an event-related design, with the intent of contrasting spatial and temporal features of the BOLD signal. In both experiments, the subject's behavior was guided by visual biofeedback of their ankle flexion angle, using an MR-compatible fiberoptic tape. From Experiment 1, we found electromyography (EMG) difference voltage ratio of approximately 2:1 for large (40 degrees ) and small (15 degrees ) dorsiflexion, 0.13 mV and 0.07 mV, respectively. In Experimental 2, we found the peak BOLD % signal changes of 1.04% and 0.89%, for large (40 degrees ) and small (15 degrees ) dorsiflexion, respectively. In addition, graded dorsiflexion produced graded BOLD signals in the primary sensorimotor and supplementary motor areas in 10 of 12 healthy young subjects, attesting to the feasibility of lower-limb fMRI at 1.5 T. This study provides insight into the cortical network involved in dorsiflexion using an experimental paradigm that is likely to translate effectively to hemiparetic stroke subjects.

During a breath hold (BH) challenge, functional MR imaging using flow-sensitive alternating inversion recovery (FAIR) and blood oxygenation level dependent (BOLD) contrast was performed with simultaneous near-infrared spectroscopy (NIRS). Time courses for the BOLD signal, cerebral blood flow (CBF), absolute deoxyhemoglobin (Hb) concentration, and relative concentration changes for total hemoglobin (HbT) were generated to (1) characterize the relationship between transient BOLD responses and the transient hemodynamic response, and (2) compare results from previous empirical animal experiments. During this mild hypercapnia task, the increase in the BOLD signal during the task indicated that an increase in CBF outweighed the competing effect of a volume-induced increase in Hb. After the task, the increase in the concentration of Hb mirrored the posttask undershoot in the BOLD and CBF data. Finally, we found a strong linear relationship between R(2)(*) and absolute Hb, except for outlier points in the Hb time series corresponding to the task cessation, which suggests there are differences in measurement sensitivity between BOLD and NIRS.

Purpose Determine whether white matter signal fluctuation on T2* weighted BOLD contrast images are associated with aging and cerebral small vessel disease (SVD). Methodology Resting state BOLD data were collected with a 250 ms repetition time (TR) to achieve unaliased, ungated cardiac sampled BOLD (cs-BOLD) images on 11 young adult controls, 10 healthy older adult controls and 7 adults with extensive white matter hyperintensities (WMH) from SVD. Tissue classes (WM and GM) were segmented on T1 images. WMH were identified on FLAIR images in the SVD group. Raw physiological noise (σphysio) and cardiac pulsatility (i.e. fluctuations at the cardiac frequency) were calculated voxel wise and group differences were tested by ANOVA. It was also possible to calculate σphysio in 2s TR cardiac aliased whole-brain BOLD (wb-BOLD) data (N = 84) obtained from the International Consortium for Brain Mapping. Results CS-BOLD metrics showed an aging and SVD effects (p

BACKGROUND: Opioids have been linked to limbic system activation and, in animals, to neurotoxicity. Limbic system nonpharmacologic activation patterns have been linked to the Apolipoprotein E (ApoE) allelic distribution. We tested the hypothesis that, in the absence of surgery, small doses of remifentanil produce limbic system activation in humans which varies with dose and ApoE genotype. METHODS: Twenty-seven ASA I-II volunteers received a remifentanil (Ultiva) infusion at four sequentially increasing doses: 0, 0.05, 0.1, and 0.2 microg x kg(-1) x min(-1) while receiving 100% oxygen. Cerebral blood flow (CBF) was measured at each dose globally and in the amygdala, cingulate, hippocampus, insula, and thalamus regions by pulsed arterial spin labeling magnetic resonance imaging. ApoE single nucleotide polymorphisms were determined in each subject. RESULTS: Significant dose-related CBF increases, without correction for Paco(2), were detected in all areas. After normalizing for global CBF to correct for Paco(2) effects, the remifentanil-mediated increased CBF in the cingulate persisted, with decreased flow occurring in the hippocampus and amygdala. All these Paco(2)-corrected effects were reversed in the presence of the ApoE4 polymorphism. CONCLUSION: Remifentanil at sedative doses produces both activating and depressing effects in various limbic system structures. The cingulate cortex seems to have the most susceptibility to remifentanil activation, and ApoE4 seems to produce relative activation of the hippocampus and amygdala.

Background Voxel-based analyses are pervasive across the range of neuroimaging techniques. In the case of perfusion imaging using arterial spin labelling (ASL), a low signal-to-noise technique, there is a tradeoff between the contrast-to-noise required to detect a perfusion abnormality and its spatial localisation. In exploratory studies, the use of an a priori region of interest (ROI), which has the benefit of averaging multiple voxels, may not be justified. Thus the question considered in this study pertains to the sample size that is required to detect a voxel-level perfusion difference between groups and two algorithms are considered. New method Empirical 3T ASL data were acquired from 25 older adults and simulations were performed based on the group template cerebral blood flow (CBF) images. General linear model (GLM) and permutation-based algorithms were tested for their ability to detect a predefined hypoperfused ROI. Simulation parameters included: inter and intra-subject variability, degree of hypoperfusion and sample size. The true positive rate was used as a measure of sensitivity. Results For a modest group perfusion difference, i.e., 10%, 37 participants per group were required when using the permutation-based algorithm, whereas 20 participants were required for the GLM-based algorithm. Comparison with existing methods This study advances the perfusion power calculation literature by considering a voxel-wise analysis with correction for multiple comparison. Conclusions The sample size requirement to detect group differences decreased exponentially in proportion to increased degree of hypoperfusion. In addition, sensitivity to detect a perfusion abnormality was influenced by the choice of algorithm.

Introduction Dementia with Lewy bodies (DLB) and Corticobasal Syndrome (CBS) are atypical parkinsonian disorders with fronto-subcortical and posterior cognitive dysfunction as common features. While visual hallucinations are a good predictor of Lewy body pathology and are rare in CBS, they are not exhibited in all cases of DLB. Given the clinical overlap between these disorders, neuropsychological and imaging markers may aid in distinguishing these entities. Methods Prospectively recruited case–control cohorts of CBS (n =31) and visual hallucination-free DLB (n =30), completed neuropsychological and neuropsychiatric measures as well as brain perfusion single-photon emission computed tomography and structural magnetic resonance imaging (MRI). Perfusion data were available for forty-two controls. Behavioural, perfusion, and cortical volume and thickness measures were compared between the groups to identify features that serve to differentiate them. Results The Lewy body with no hallucinations group performed more poorly on measures of episodic memory compared to the corticobasal group, including the delayed and cued recall portions of the California Verbal Learning Test (F (1, 42) =23.1, P