Concurrent intrinsic optical imaging and fMRI at ultra-high field using magnetic field proof optical components.

Intrinsic optical imaging (IOI) is a well established technique to quantify activation-related hemodynamical changes at the surface of the brain, which can be used to investigate the underlying processes of BOLD signal formation. To directly and quantitatively relate IOI and fMRI, simultaneous measurements with the two modalities are necessary. Here, a novel technical solution for a completely in-bore setup is presented, which uses only magnetic field proof components and thus allows concurrent recordings with a quality similar to that obtained in separate experiments. Measurements of the somatosensory cortex of rats with electrical forepaw stimulation were used to verify this approach. The high spatial and temporal resolution of the fMRI data, which is possible due to the high magnetic field of 14.1 T, the use of a point-spread function-based distortion correction and optimized additional anatomical images, allowed accurate colocalization of the images of the two modalities. Accordingly, detailed investigations of the temporal and spatial relationships between the hemodynamic parameters and the fMRI signal, which demonstrate the linear dependence of the BOLD effect on changes in the concentrations of oxygenated and deoxygenated hemoglobin, are possible. Comparisons between the signals emerging from arterial, venous and parenchymal areas are possible and show clearly distinct characteristics. The presented setup allows combining MRI measurements and optical recordings without serious losses in the data quality of either modality. While the proposed combination of fMRI and IOI can help to gain valuable insight into the generation of the BOLD effect, the setup can be easily modified to include different types of optical or MRI measurements.

Mutual benefit achieved by combining ultralow-field magnetic resonance and hyperpolarizing techniques.

Ultralow-field (ULF) nuclear magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) are promising spectroscopy and imaging methods allowing for, e.g., the simultaneous detection of multiple nuclei or imaging in the vicinity of metals. To overcome the inherently low signal-to-noise ratio that usually hampers a wider application, we present an alternative approach to prepolarized ULF MRS employing hyperpolarization techniques like signal amplification by reversible exchange (SABRE) or Overhauser dynamic nuclear polarization (ODNP). Both techniques allow continuous hyperpolarization of 1H as well as other MR-active nuclei. For the implementation, a superconducting quantum interference device (SQUID)-based ULF MRS/MRI detection scheme was constructed. Due to the very low intrinsic noise level, SQUIDs are superior to conventional Faraday detection coils at ULFs. Additionally, the broadband characteristics of SQUIDs enable them to simultaneously detect the MR signal of different nuclei such as 13C, 19F, or 1H. Since SQUIDs detect the MR signal directly, they are an ideal tool for a quantitative investigation of hyperpolarization techniques such as SABRE or ODNP.

Simultaneous epidural functional near-infrared spectroscopy and cortical electrophysiology as a tool for studying local neurovascular coupling in primates.

Simultaneous measurements of intra-cortical electrophysiology and hemodynamic signals in primates are essential for relating human neuroimaging studies with intra-cortical electrophysiology in monkeys. Previously, technically challenging and resourcefully demanding techniques such as fMRI and intrinsic-signal optical imaging have been used for such studies. Functional near-infrared spectroscopy is a relatively less cumbersome neuroimaging method that uses near-infrared light to detect small changes in concentrations of oxy-hemoglobin (HbO), deoxy-hemoglobin (HbR) and total hemoglobin (HbT) in a volume of tissue with high specificity and temporal resolution. FNIRS is thus a good candidate for hemodynamic measurements in primates to acquire local hemodynamic signals during electrophysiological recordings. To test the feasibility of using epidural fNIRS with concomitant extracellular electrophysiology, we recorded neuronal and hemodynamic activity from the primary visual cortex of two anesthetized monkeys during visual stimulation. We recorded fNIRS epidurally, using one emitter and two detectors. We performed simultaneous cortical electrophysiology using tetrodes placed between the fNIRS sensors. We observed robust and reliable responses to the visual stimulation in both [HbO] and [HbR] signals, and quantified the signal-to-noise ratio of the epidurally measured signals. We also observed a positive correlation between stimulus-induced modulation of [HbO] and [HbR] signals and strength of neural modulation. Briefly, our results show that epidural fNIRS detects single-trial responses to visual stimuli on a trial-by-trial basis, and when coupled with cortical electrophysiology, is a promising tool for studying local hemodynamic signals and neurovascular coupling.

Sick sinus syndrome in HCN1-deficient mice.

BACKGROUND: Sinus node dysfunction (SND) is a major clinically relevant disease that is associated with sudden cardiac death and requires surgical implantation of electric pacemaker devices. Frequently, SND occurs in heart failure and hypertension, conditions that lead to electric instability of the heart. Although the pathologies of acquired SND have been studied extensively, little is known about the molecular and cellular mechanisms that cause congenital SND. METHODS AND RESULTS: Here, we show that the HCN1 protein is highly expressed in the sinoatrial node and is colocalized with HCN4, the main sinoatrial pacemaker channel isoform. To characterize the cardiac phenotype of HCN1-deficient mice, a detailed functional characterization of pacemaker mechanisms in single isolated sinoatrial node cells, explanted beating sinoatrial node preparation, telemetric in vivo electrocardiography, echocardiography, and in vivo electrophysiology was performed. On the basis of these experiments we demonstrate that mice lacking the pacemaker channel HCN1 display congenital SND characterized by bradycardia, sinus dysrhythmia, prolonged sinoatrial node recovery time, increased sinoatrial conduction time, and recurrent sinus pauses. As a consequence of SND, HCN1-deficient mice display a severely reduced cardiac output. CONCLUSIONS: We propose that HCN1 stabilizes the leading pacemaker region within the sinoatrial node and hence is crucial for stable heart rate and regular beat-to-beat variation. Furthermore, we suggest that HCN1-deficient mice may be a valuable genetic disease model for human SND.