Evidence of cerebral hypoperfusion consecutive to ultrasound-mediated blood-brain barrier opening in rats.

PURPOSE: This work aims to explore the effect of Blood Brain Barrier (BBB) opening using ultrasound combined with microbubbles injection on cerebral blood flow in rats. METHODS: Two groups of n = 5 rats were included in this study. The first group was used to investigate the impact of BBB opening on the Arterial Spin Labeling (ASL) signal, in particular on the arterial transit time (ATT). The second group was used to analyze the spatiotemporal evolution of the change in cerebral blood flow (CBF) over time following BBB opening and validate these results using DSC-MRI. RESULTS: Using pCASL, a decrease in CBF of up to 29 . 6 ± 15 . 1 % $$ 29.6\pm 15.1\% $$ was observed in the target hemisphere, associated with an increase in arterial transit time. The latter was estimated to be 533 ± 121ms $$ 533\pm 12\mathrm{1ms} $$ in the BBB opening impacted regions against 409 ± 93ms $$ 409\pm 93\mathrm{ms} $$ in the contralateral hemisphere. The spatio-temporal analysis of CBF maps indicated a nonlocal hypoperfusion. DSC-MRI measurements were consistent with the obtained results. CONCLUSION: This study provided strong evidence that BBB opening using microbubble intravenous injection induces a transient hypoperfusion. A spatiotemporal analysis of the hypoperfusion changes allows to establish some points of similarity with the cortical spreading depression phenomenon.

SAR comparison between CASL and pCASL at high magnetic field and evaluation of the benefit of a dedicated labeling coil.

PURPOSE: To investigate the heating induced by (pseudo)-continuous arterial spin labeling ((p)CASL) sequences in vivo at 9.4T and to evaluate the benefit of a dedicated labeling coil. METHODS: Temperature was measured continuously in the brain, neck, and rectum of 9 rats with fiber-optic temperature probes while running pCASL-EPI and CASL-EPI sequences, with labeling B1 amplitudes (B1ave ) of 3, 5, and 7 µT and using a dedicated labeling RF coil or a volume coil. From the temperature time courses, the corresponding specific absorption rate (SAR) was computed. A trade-off between SAR and labeling quality was determined based on measured inversion efficiencies. RESULTS: ASL experiments with standard parameters (B1ave = 5 µT, Tacq = 4 min, labeling with volume coil) lead to a brain temperature increase due to RF of 0.72 ± 0.46 K for pCASL and 0.25 ± 0.17 K for CASL. Using a dedicated labeling coil reduced the RF-induced SAR by a factor of 10 in the brain and a factor of 2 in the neck. Besides SAR due to RF, heat from the coil decoupling circuits produced significant temperature increases. When labeling with a dedicated coil, this mechanism was the dominant source of brain heating. At equivalent RF-SAR, CASL provided slightly superior label efficiency to pCASL and is therefore the preferred sequence when an ASL coil is available. CONCLUSION: B1ave = 4-5 µT provided a good compromise between label efficiency and SAR, both for pCASL and CASL. The sensitivity of animals to heating should be taken into account when optimizing preclinical ASL protocols and may require reducing scan duration or lowering B1ave .

Interpulse phase corrections for unbalanced pseudo-continuous arterial spin labeling at high magnetic field.

PURPOSE: To evaluate a prescan-based radiofrequency phase-correction strategy for unbalanced pseudo-continuous arterial spin labeling (pCASL) at 9.4 T in vivo and to test its robustness toward suboptimal shim conditions. METHODS: Label and control interpulse phases were optimized separately by means of two prescans in rats. The mean perfusion as well as the interhemispherical symmetry were measured for several phase combinations (optimized versus theoretical phases) to evaluate the correction quality. Interpulse phases were also optimized under degraded shim conditions (i.e., up to four times the study shim values) to test the strategy's robustness. RESULTS: For all tested shim conditions, the full arterial spin labeling (ASL) signal could be restored. Without any correction, the relative ASL signal was 1.4 ± 1.7%. It increased to 3.6 ± 1.4% with an optimized label phase and to 5.3 ± 1.2% with optimized label and control phases. Moreover, asymmetry between brain hemispheres, which could be as high as 100% without phase optimization, was dramatically reduced to 1 ± 3% when applying optimized label and control phases. CONCLUSIONS: Pseudo-continuous ASL at high magnetic field is very sensitive to shim conditions. Label and control radiofrequency phase optimization based on prescans robustly maximizes the ASL signal obtained with unbalanced pCASL and minimizes the asymmetry between hemispheres. Magn Reson Med 79:1314-1324, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Transit time mapping in the mouse brain using time-encoded pCASL.

The cerebral blood flow (CBF) is a potential biomarker for neurological disease. However, the arterial transit time (ATT) of the labeled blood is known to potentially affect CBF quantification. Furthermore, ATT could be an interesting biomarker in itself, as it may reflect underlying macro- and microvascular pathologies. Currently, no optimized magnetic resonance imaging (MRI) sequence exists to measure ATT in mice. Recently, time-encoded labeling schemes have been implemented in rats and humans, enabling ATT mapping with higher signal-to-noise ratio (SNR) and shorter scan time than multi-delay arterial spin labeling (ASL). In this study, we show that time-encoded pseudo-continuous arterial spin labeling (te-pCASL) also enables transit time measurements in mice. As an optimal design that takes the fast blood flow in mice into account, time encoding with 11 sub-boli of 50 ms is proposed to accurately probe the inflow of labeled blood. For perfusion imaging, a separate, traditional pCASL scan was employed. From the six studied brain regions, the hippocampus showed the shortest ATT (169 ± 11 ms) and the auditory/visual cortex showed the longest (284 ± 16 ms). Furthermore, ATT was found to be preserved in old wild-type mice. In a mouse with an induced carotid artery occlusion, prolongation of ATT was shown. In conclusion, this study shows the successful implementation of te-pCASL in mice, making it possible, for the first time, to measure ATT in mice in a time-efficient manner.

Impact of tissue T1 on perfusion measurement with arterial spin labeling.

PURPOSE: Arterial spin labeling (ASL) may provide quantitative maps of cerebral blood flow (CBF). Because labeled water exchanges with tissue water, this study evaluates the influence of tissue T1 on CBF quantification using ASL. METHODS: To locally modify T1 , a low dose of manganese (Mn) was intracerebrally injected in one hemisphere of 19 rats (cortex or striatum). Tissue T1 and CBF were mapped using inversion recovery and continuous ASL experiments at 4.7T. RESULTS: Mn reduced the tissue T1 by more than 30% but had little impact on other tissue properties as assessed via dynamic susceptibility and diffusion MRI. Using a single-compartment model, the use of a single tissue T1 value yielded a mean relative ipsilateral (Mn-injected) to contralateral (noninjected) CBF difference of -34% in cortex and -22% in striatum tissue. With a T1 map, these values became -7% and +8%, respectively. CONCLUSION: A low dose of Mn reduces the tissue T1 without modifying CBF. Heterogeneous T1 impacts the ASL estimate of CBF in a region-dependent way. In animals, and when T1 modifications exceed the accuracy with which the tissue T1 can be determined, an estimate of tissue T1 should be obtained when quantifying CBF with an ASL technique. Magn Reson Med 77:1656-1664, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

BOLD fMRI of cerebrovascular reactivity in the middle cerebral artery territory: A 100 volunteers' study.

BACKGROUND AND PURPOSE: The assessment of cerebrovascular reactivity (CVR) has shown promising results for its use in medical diagnosis and prognosis, especially in patients suffering from severe intracranial arterial stenosis. However, its quantification remains uncertain because of a large variability inherent in brain anatomy and in methodological settings. To overcome this variability, we provide lateralization index (LI) values for CVR within the middle cerebral artery territory to detect CVR impairment. MATERIALS AND METHODS: We assessed CVR in 100 volunteers (41 females; 47.52 ± 21.58 years) without cervico-encephalic arterial stenosis using BOLD-fMRI contrast with a block-design hypercapnic challenge. Averaged end-tidal CO2 was used as a physiological regressor for statistical analyses with a general linear model. We measured %BOLD signal-change in segmented gray matter regions of interest in the middle cerebral artery territory (MCA). We calculated a laterality index according to the following formula: LI=(CVRleft-CVRright)/(CVRleft+CVRright). We tested the effects of methodological settings (i.e. hypercapnic gas, gas administration means, MR acquisition and sex) on %BOLD signal change and LI values with analysis of variance. RESULTS: No adverse effects of the hypercapnic challenge were reported. LI values were independent of experimental conditions. Mean LI calculated in MCA territories was 0.016 ± 0.031, giving the lower and upper limits of 95% (m ± 2SD) of this population distribution at]-0.05; 0.08[. CONCLUSION: LI can effectively help us to overcome measurement variabilities. Therefore, it can be used to detect abnormal asymmetries in CVR and identify patients at higher risk of ischemic stroke.

Loss of spontaneous vasomotion precedes impaired cerebrovascular reactivity and microbleeds in a mouse model of cerebral amyloid angiopathy.

Background: Cerebral amyloid angiopathy (CAA) is a cerebral small vessel disease in which amyloid-ß accumulates in vessel walls. CAA is a leading cause of symptomatic lobar intracerebral hemorrhage and an important contributor to age-related cognitive decline. Recent work has suggested that vascular dysfunction may precede symptomatic stages of CAA, and that spontaneous slow oscillations in arteriolar diameter (termed vasomotion), important for amyloid-ß clearance, may be impaired in CAA. Methods: To systematically study the progression of vascular dysfunction in CAA, we used the APP23 mouse model of amyloidosis, which is known to develop spontaneous cerebral microbleeds mimicking human CAA. Using in vivo 2-photon microscopy, we longitudinally imaged unanesthetized APP23 transgenic mice and wildtype littermates from 7 to 14 months of age, tracking amyloid-ß accumulation and vasomotion in individual pial arterioles over time. MRI was used in separate groups of 12-, 18-, and 24-month-old APP23 transgenic mice and wildtype littermates to detect microbleeds and to assess cerebral blood flow and cerebrovascular reactivity with pseudo-continuous arterial spin labeling. Results: We observed a significant decline in vasomotion with age in APP23 mice, while vasomotion remained unchanged in wildtype mice with age. This decline corresponded in timing to initial vascular amyloid-ß deposition (∼8-10 months of age), although was more strongly correlated with age than with vascular amyloid-ß burden in individual arterioles. Declines in vasomotion preceded the development of MRI-visible microbleeds and the loss of smooth muscle actin in arterioles, both of which were observed in APP23 mice by 18 months of age. Additionally, evoked cerebrovascular reactivity was intact in APP23 mice at 12 months of age, but significantly lower in APP23 mice by 24 months of age. Conclusions: Our findings suggest that a decline in spontaneous vasomotion is an early, potentially pre-symptomatic, manifestation of CAA and vascular dysfunction, and a possible future treatment target.

Changes in cerebral blood flow and vasoreactivity to CO2 measured by arterial spin labeling after 6days at 4350m.

Changes in cerebral perfusion and CO2 cerebrovascular reactivity during and immediately after a sojourn at high altitude remain unclear but may be critical for acclimatization. The aim of the present study was to assess the effects of 6days at 4350m on cerebral perfusion and cerebrovascular reactivity (CVR) to CO2 by arterial spin labeling (ASL) magnetic resonance imaging at sea level and to compare it with transcranial Doppler (TCD) results at altitude. Eleven healthy male subjects, non-acclimatized to altitude, stayed for 6days at 4350m (Observatoire Vallot, massif du Mont-Blanc). Prior to the stay and within 6h after returning to sea level, subjects were investigated using pseudo-continuous ASL at 3T during a block-design inhalation paradigm to measure basal cerebral blood flow (CBF) and CO2 CVR. End-tidal CO2 (PetCO2), respiratory rate, heart rate and oxygen saturation were recorded during the exam. Subjects were also examined using TCD prior to and on day 5 of the stay at altitude to measure blood velocity in the middle cerebral artery (MCAv) and CO2 CVR. CO2 CVR was expressed as percent change in ASL CBF or TCD MCAv per mmHg change in PetCO2. PetCO2 was significantly decreased during and after altitude. Significant increases in TCD MCAv compared to before altitude measurements were observed on day 5 at altitude (+20.5±15.5%). Interestingly, ASL CBF remained increased in the MCA and anterior vascular territories (+22.0±24.1% and 20.5±20.3%, respectively) after altitude under normoxic conditions. TCD CVR tended to decrease on day 5 at 4350m (-12.3±54.5% in the MCA) while the ASL CVR was significantly decreased after altitude (-29.5±19.8% in the MCA). No correlation was observed between cerebral hemodynamic changes and symptoms of acute mountain sickness at high altitude. In conclusion, prolonged exposure to high altitude significantly increases blood flow during the altitude stay and within 6h after returning to sea level. Decreased CO2 CVR after prolonged altitude exposure was also observed using ASL. Changes in cerebral hemodynamics with altitude exposure probably involve other mechanisms than the vasodilatory effect of hypoxia only, since it persists under normoxia several hours following the descent.

Head holder and cranial window design for sequential magnetic resonance imaging and optical imaging in awake mice.

Medical imaging techniques are widely used in preclinical research as diagnostic tools to detect physiological abnormalities and assess the progression of neurovascular disease in animal models. Despite the wealth of imaging options in magnetic resonance imaging (MRI), interpretation of imaging-derived parameters regarding underlying tissue properties is difficult due to technical limitations or lack of parameter specificity. To address the challenge of interpretation, we present an animal preparation protocol to achieve quantitative measures from both MRI and advanced optical techniques, including laser speckle contrast imaging and two-photon microscopy, in murine models. In this manner, non-translatable methods support and improve interpretation of less specific, translatable methods, i.e., MRI. Combining modalities for improved clinical interpretation involves satisfying the requirements of various methods. Furthermore, physiology unperturbed by anesthetics is a prerequisite for the strategy to succeed. Awake animal imaging with restraint provides an alternative to anesthesia and facilitates translatability of cerebral measurements. The method outlines design requirements for the setup and a corresponding reproducible surgical procedure for implanting a 3D printed head holder and cranial window to enable repeated multimodal imaging. We document the development, application, and validation of the method and provide examples confirming the usefulness of the design in acquiring high quality data from multiple modalities for quantification of a wide range of metrics of cerebral physiology in the same animal. The method contributes to preclinical small animal imaging, enabling sequential imaging of previously mutually exclusive techniques.

High-resolution relaxometry-based calibrated fMRI in murine brain: Metabolic differences between awake and anesthetized states.

Functional magnetic resonance imaging (fMRI) techniques using the blood-oxygen level-dependent (BOLD) signal have shown great potential as clinical biomarkers of disease. Thus, using these techniques in preclinical rodent models is an urgent need. Calibrated fMRI is a promising technique that can provide high-resolution mapping of cerebral oxygen metabolism (CMRO2). However, calibrated fMRI is difficult to use in rodent models for several reasons: rodents are anesthetized, stimulation-induced changes are small, and gas challenges induce noisy CMRO2 predictions. We used, in mice, a relaxometry-based calibrated fMRI method which uses cerebral blood flow (CBF) and the BOLD-sensitive magnetic relaxation component, R2', the same parameter derived in the deoxyhemoglobin-dilution model of calibrated fMRI. This method does not use any gas challenges, which we tested on mice in both awake and anesthetized states. As anesthesia induces a whole-brain change, our protocol allowed us to overcome the former limitations of rodent studies using calibrated fMRI. We revealed 1.5-2 times higher CMRO2, dependent upon brain region, in the awake state versus the anesthetized state. Our results agree with alternative measurements of whole-brain CMRO2 in the same mice and previous human anesthesia studies. The use of calibrated fMRI in rodents has much potential for preclinical fMRI.

Optimized cervical spinal cord perfusion MRI after traumatic injury in the rat.

Despite the potential to guide clinical management of spinal cord injury and disease, noninvasive methods of monitoring perfusion status of the spinal cord clinically remain an unmet need. In this study, we optimized pseudo-continuous arterial spin labeling (pCASL) for the rodent cervical spinal cord and demonstrate its utility in identifying perfusion deficits in an acute contusion injury model. High-resolution perfusion sagittal images with reduced imaging artifacts were obtained with optimized background suppression and imaging readout. Following moderate contusion injury, perfusion was clearly and reliably decreased at the site of injury. Implementation of time-encoded pCASL confirmed injury site perfusion deficits with blood flow measurements corrected for variability in arterial transit times. The noninvasive protocol of pCASL in the spinal cord can be utilized in future applications to examine perfusion changes after therapeutic interventions in the rat and translation to patients may offer critical implications for patient management.

Neurogliovascular dysfunction in a model of repeated traumatic brain injury.

Traumatic brain injury (TBI) research has focused on moderate to severe injuries as their outcomes are significantly worse than those of a mild TBI (mTBI). However, recent epidemiological evidence has indicated that a series of even mild TBIs greatly increases the risk of neurodegenerative and psychiatric disorders. Neuropathological studies of repeated TBI have identified changes in neuronal ionic concentrations, axonal injury, and cytoskeletal damage as important determinants of later life neurological and mood compromise; yet, there is a paucity of data on the contribution of neurogliovascular dysfunction to the progression of repeated TBI and alterations of brain function in the intervening period. Methods: Here, we established a mouse model of repeated TBI induced via three electromagnetically actuated impacts delivered to the intact skull at three-day intervals and determined the long-term deficits in neurogliovascular functioning in Thy1-ChR2 mice. Two weeks post the third impact, cerebral blood flow and cerebrovascular reactivity were measured with arterial spin labelling magnetic resonance imaging. Neuronal function was investigated through bilateral intracranial electrophysiological responses to optogenetic photostimulation. Vascular density of the site of impacts was measured with in vivo two photon fluorescence microscopy. Pathological analysis of neuronal survival and astrogliosis was performed via NeuN and GFAP immunofluorescence. Results: Cerebral blood flow and cerebrovascular reactivity were decreased by 50±16% and 70±20%, respectively, in the TBI cohort relative to sham-treated animals. Concomitantly, electrophysiological recordings revealed a 97±1% attenuation in peri-contusional neuronal reactivity relative to sham. Peri-contusional vascular volume was increased by 33±2% relative to sham-treated mice. Pathological analysis of the peri-contusional cortex demonstrated astrogliosis, but no changes in neuronal survival. Conclusion: This work provides the first in-situ characterization of the long-term deficits of the neurogliovascular unit following repeated TBI. The findings will help guide the development of diagnostic markers as well as therapeutics targeting neurogliovascular dysfunction.

Multiparametric Magnetic Resonance Investigation of Brain Adaptations to 6 Days at 4350 m.

OBJECTIVE: Hypoxic exposure in healthy subjects can induce acute mountain sickness including headache, lethargy, cerebral dysfunction, and substantial cerebral structural alterations which, in worst case, can lead to potentially fatal high altitude cerebral edema. Within this context, the relationships between high altitude-induced cerebral edema, changes in cerebral perfusion, increased brain parenchyma volume, increased intracranial pressure, and symptoms remain unclear. METHODS: In 11 subjects before and after 6 days at 4350 m, we performed multiparametric magnetic resonance investigations including anatomical, apparent diffusion coefficient and arterial spin labeling sequences. RESULTS: After the altitude stay, while subjects were asymptomatic, white matter volume (+0.7 ± 0.4%, p = 0.005), diffusion (+1.7 ± 1.4%, p = 0.002), and cerebral blood flow (+28 ± 38%; p = 0.036) were significantly increased while cerebrospinal fluid volume was reduced (-1.4 ± 1.1%, p = 0.009). Optic nerve sheath diameter (used as an index of increased intracranial pressure) was unchanged from before (5.84 ± 0.53 mm) to after (5.92 ± 0.60 mm, p = 0.390) altitude exposure. Correlations were observed between increases in white matter volume and diffusion (rho = 0.81, p = 0.016) and between changes in CSF volume and changes in ONSD s (rho = -0.92, p = 0.006) and symptoms during the altitude stay (rho = -0.67, p = 0.031). CONCLUSIONS: These data demonstrate white matter alterations after several days at high altitude when subjects are asymptomatic that may represent the normal brain response to prolonged high altitude exposure.

Cerebral volumetric changes induced by prolonged hypoxic exposure and whole-body exercise.

The present study assessed the isolated and synergetic effects of hypoxic exposure and prolonged exercise on cerebral volume and subedema and symptoms of acute mountain sickness (AMS). Twelve healthy males performed three semirandomized blinded 11-hour sessions with (1) an inspiratory oxygen fraction (FiO2) of 12% and 4-hour cycling, (2) FiO2=21% and 4-hour cycling, and (3) FiO2=8.5% to 12% at rest (matching arterial oxygen saturation measured during the first hypoxic session). Volumetric, apparent diffusion coefficient (ADC), and arterial spin labelling 3T magnetic resonance imaging sequences were performed after 30 minutes and 10 hours in each session. Thirty minutes of hypoxia at rest induced a significant increase in white-matter volume (+0.8±1.0% compared with normoxia) that was exacerbated after 10 hours of hypoxia at rest (+1.5±1.1%) or with cycling (+1.6±1.1%). Total brain parenchyma volume increased significantly after 10 hours of hypoxia with cycling only (+1.3±1.1%). Apparent diffusion coefficient was significantly reduced after 10 hours of hypoxia at rest or with cycling. No significant change in cerebral blood flow was observed. These results demonstrate changes in white-matter volume as early as after 30 minutes of hypoxia that worsen after 10 hours, probably due to cytotoxic edema. Exercise accentuates the effect of hypoxia by increasing total brain volume. These changes do not however correlate with AMS symptoms.

Reducing contamination while closing the gap: BASSI RF pulses in PASL.

Bandwidth-modulated selective saturation and inversion (BASSI) pulses are a class of frequency- and gradient-modulated radiofrequency (RF) pulses, derived from the hyperbolic secant pulse by temporal variation of the bandwidth parameter. These pulses afford optimal amplitude modulation, achieving uniform and highly selective profiles at any effective flip angle. In this paper, BASSI pulses are parameterized to obtain low RF energy pulsed arterial spin labeling (PASL) label pulses with minimal contamination of static spins outside the label region and highly selective PICORE/QUIPSS II saturation pulses allowing for small label gaps. They are compared to frequency offset corrected inversion (FOCI) label pulses and sinc saturation pulses in simulations and a phantom experiment. Drawing on the outstanding selectivity of bandwidth-modulated saturation pulses, a new noninvasive method to measure in vivo the contamination effects due to direct and indirect saturation of static spins by the label pulse is presented. In an in vivo study on four subjects, contamination effects in a QUIPSS II PASL implementation based on BASSI pulses are compared to those present in a state-of-the-art Q2TIPS sequence employing a FOCI label pulse. Residual contamination in the QUIPSS II/BASSI sequence is shown to be reduced by a factor of 3, compared to the Q2TIPS/FOCI sequence. In vivo human perfusion images obtained with a label gap of only 2 mm are presented.

The effect of global cerebral vasodilation on focal activation hemodynamics.

In view of the potential of global resting blood flow level to confound the interpretation of blood oxygenation level-dependent (BOLD) fMRI studies, we investigated the effect of pronounced elevation in baseline cerebral blood flow (CBF) on BOLD and CBF responses to functional activation. Twelve healthy volunteers performed bilateral finger apposition while attending to a radial yellow/blue checkerboard. Three levels of global CBF increase were achieved by inhaling 5, 7.5 or 10% CO2. CBF and BOLD signals were simultaneously quantified using interleaved multi-slice pulsed arterial spin labeling (PASL) and T2*-weighted gradient echo sequences. Increasing basal CBF produced a significant decrease in the activation-induced BOLD response, with the slope of the optimal linear fit of activation versus basal BOLD signal changes of -0.32 +/- 0.01%/% for motor and visual cortex regions of interest (ROIs). While the modulation in basal flow level also produced a statistically significant effect on the activation-induced CBF change, the degree of relative attenuation of the flow response was slight, with a slope of -0.18 +/- 0.02%/% in the motor and -0.13 +/- 0.01%/% in the visual cortex ROI. The current findings describe a strong attenuation of the BOLD response at significantly elevated basal flow levels and call for independent quantification of resting CBF in BOLD fMRI studies that involve subjects and/or conditions with markedly elevated global perfusion.

Hemodynamic and metabolic responses to activation, deactivation and epileptic discharges.

To investigate the coupling between the hemodynamic and metabolic changes following functional brain activation as well as interictal epileptiform discharges (IEDs), blood oxygenation level dependent (BOLD), perfusion and oxygen consumption responses to a unilateral distal motor task and interictal epileptiform discharges (IEDs) were examined via continuous EEG-fMRI. Seven epilepsy patients performed a periodic (1 Hz) right-hand pinch grip using approximately 8% of their maximum voluntary contraction, a paradigm previously shown to produce contralateral MI neuronal excitation and ipsilateral MI neuronal inhibition. A multi-slice interleaved pulsed arterial spin labeling and T(2)*-weighted gradient echo sequence was employed to quantify cerebral blood flow (CBF) and BOLD changes. EEG was recorded throughout the imaging session and reviewed to identify the IEDs. During the motor task, BOLD, CBF and cerebral metabolic rate of oxygen consumption (CMR(O(2))) signals increased in the contra- and decreased in the ipsilateral primary motor cortex. The relative changes in CMR(O(2)) and CBF were linearly related, with a slope of 0.46 +/- 0.05. The ratio of contra- to ipsilateral CBF changes was smaller in the present group of epilepsy patients than in the healthy subjects examined previously. IEDs produced both increases and decreases in BOLD and CBF signals. In the two case studies for which the estimation criteria were met, the coupling ratio between IED-induced CMR(O(2)) and CBF changes was estimated at 0.48 +/- 0.17. These findings provide evidence for a preserved coupling between hemodynamic and metabolic changes in response to both functional activation and, for the two case studies available, in response to interictal epileptiform activity.

Bandwidth-modulated adiabatic RF pulses for uniform selective saturation and inversion.

Radiofrequency (RF) inversion and saturation pulses with extremely high spatial selectivity and uniform profiles are a requirement for numerous MR techniques, such as pulsed arterial spin labeling and outer volume suppression. Adiabatic pulses used for inversion of longitudinal magnetization are ubiquitous, but the superior selectivity of adiabatic full passages has not been widely exploited for saturation because a simple way of calibrating the amplitude of these subadiabatic pulses is lacking. An analytically derived calibration equation is presented, applicable to a large class of pulses including the hyperbolic secant (HS) pulse and allowing the determination of the precise amplitude required to achieve any effective flip angle. The properties of this calibration are examined, and a highly selective and homogeneous HS saturation pulse is demonstrated. Based on this calibration a new class of RF pulses is developed. These bandwidth-modulated adiabatic selective saturation and inversion (BASSI) RF pulses afford optimal amplitude modulation, achieving uniform profiles at any effective flip angle. BASSI pulses are compared to existing gradient modulated adiabatic pulses in simulations and phantom experiments and shown to be superior in terms of selectivity and homogeneity, while requiring less RF energy. An application of BASSI pulses to pulsed arterial spin labeling is shown.

Hemodynamic and metabolic responses to neuronal inhibition.

Functional magnetic resonance imaging (fMRI) was used to investigate the changes in blood oxygenation level dependent (BOLD) signal, cerebral blood flow (CBF) and cerebral metabolic rate of oxygen consumption (CMR(O(2))) accompanying neuronal inhibition. Eight healthy volunteers performed a periodic right-hand pinch grip every second using 5% of their maximum voluntary contraction (MVC), a paradigm previously shown to produce robust ipsilateral neuronal inhibition. To simultaneously quantify CBF and BOLD signals, an interleaved multislice pulsed arterial spin labeling (PASL) and T(2)*-weighted gradient echo sequence was employed. The CMR(O(2)) was calculated using the deoxyhemoglobin dilution model, calibrated by data measured during graded hypercapnia. In all subjects, BOLD, CBF and CMR(O(2)) signals increased in the contralateral and decreased in the ipsilateral primary motor (M1) cortex. The relative changes in CMR(O(2)) and CBF were linearly related, with a slope of approximately 0.4. The coupling ratio thus established for both positive and negative CMR(O(2)) and CBF changes is in close agreement with the ones observed by earlier studies investigating M1 perfusion and oxygen consumption increases. These findings characterize the hemodynamic and metabolic downregulation accompanying neuronal inhibition and thereby establish the sustained negative BOLD response as a marker of neuronal deactivation.