Convertible pneumatic actuator for magnetic resonance elastography of the brain

Here we present a novel pneumatic actuator design for brain magnetic resonance elastography (MRE). Magnetic resonance elastography is a phase contrast technique capable of tracing strain wave propagation and utilizing this information for the calculation of mechanical properties of materials and living tissues. In MRE experiments, the acoustic waves are generated in a synchronized way with respect to image acquisition, using various types of mechanical actuators. The unique feature of the design is its simplicity and flexibility, which allows reconfiguration of the actuator for different applications ranging from in vivo brain MRE to experiments with phantoms. Phantom and in vivo data are presented to demonstrate actuator performance.     

Bilateral filtering of magnetic resonance phase images

High-pass filtering is required for the removal of background field inhomogeneities in magnetic resonance phase images. This high-pass filtering smooths across boundaries between areas with large differences in phase. The most prominent boundary is the surface of the brain where areas with large phase values inside the brain are located close to areas outside the brain where the phase is, on average, zero. Cortical areas, which are of great interest in brain MRI, are therefore often degraded by high-pass filtering. Here, we propose the use of the bilateral filter for the high-pass filtering step. The bilateral filter is essentially a Gaussian filter that stops smoothing at boundaries. We show that the bilateral filter improves image quality at the brain's surface, without sacrificing contrast within the brain.     

Quantum cognition: The possibility of processing with nuclear spins in the brain

The possibility that quantum processing with nuclear spins might be operative in the brain is explored. Phosphorus is identified as the unique biological element with a nuclear spin that can serve as a qubit for such putative quantum processing–a neural qubit–while the phosphate ion is the only possible qubit-transporter  . We identify the “Posner molecule”, Ca₉(PO₄)₆${\text{Ca}}_9{\left({\text{PO}}_4\right)}_6$, as the unique molecule that can protect the neural qubits on very long times and thereby serve as a (working) quantum-memory. A central requirement for quantum-processing is quantum entanglement. It is argued that the enzyme catalyzed chemical reaction which breaks a pyrophosphate ion into two phosphate ions can quantum entangle pairs of qubits. Posner molecules, formed by binding such phosphate pairs with extracellular calcium ions, will inherit the nuclear spin entanglement. A mechanism for transporting Posner molecules into presynaptic neurons during vesicle endocytosis is proposed. Quantum measurements can occur when a pair of Posner molecules chemically bind and subsequently melt, releasing a shower of intra-cellular calcium ions that can trigger further neurotransmitter release and enhance the probability of post-synaptic neuron firing. Multiple entangled Posner molecules, triggering non-local quantum correlations of neuron firing rates, would provide the key mechanism for neural quantum processing. Implications, both in vitro and in vivo, are briefly mentioned.     

Efficient One-Pot Synthesis of Doxorubicin Conjugates Through Its Amino Group to Melanotransferrin P97

Abstract

The amino group of doxorubicin 1 is reacted with bis-NHS-ester linkers 6, or anhydrides 13 to offer in high yield modified doxorubicins 7–12 and 14–16, respectively. Compounds 7–12 are mono-NHS-esters, and can be directly coupled with melanotransferrin (p97), a useful vector with the ability to cross the blood-brain barrier, to yield the expected doxorubicin-p97 conjugates. Upon activating the carboxylic group with BTTU, compound 14–16 could be used in the same reaction. Structurally, the amino group of doxorubicin is covalently bonded to the amino groups of p97. The conjugates are potential candidates for treatment of brain tumors.     

ADC measurements at low and high b values: insight into normal brain structure with clinical DWI

PURPOSE: To demonstrate drop in brain ADC measurements from low to high b values; to evaluate the structural information provided based on those changes; and to discuss the anatomical reasons for ADC differences. METHODS: Four cerebral ROI (precuneus-PRC, hippocampus-HIP, and the genu-GCC and splenium-SCC of the corpus callosum-CC) were drawn for ADC measurements with low (1000) and high (3000) b-value DWI in 50 normal subjects. ANOVA and Bonferroni correction tested ADC differences between areas, between both hemispheres, between GCC and SCC, and between b-value related ADC drop within areas. Pearson test evaluated dependence of interhemispheric and intercallosum ADC measurements obtained with the same b-value, dependence between areas of intrazonal drop, and the interhemispheric and intercallosum dependence of intrazonal drop. RESULTS: ADCs differed between areas (P<.0001). Interhemispheric ADC only differed in PRC with low b-value (P<.027). No HIP asymmetries occurred regardless the b-value. ADC drop within PRC and HIP was similar but differed (P<.0001) from ADC drop within both CC ROI. ADC drop was also different between GCC and SCC (P<.0001). In PRC and HIP, ADC showed a significant interhemispheric and intrazonal dependence (P<.0001). There was no GCC to SCC ADC dependence. Intrazonal dependence in the CC was only significant in the SCC (P<.001). Interhemispheric dependence of intrazonal drop was significant (PRC P=.007; HIP P<.0001) but failed to reach significance in the CC. CONCLUSION: Low and high b-value measurements show different diffusion behaviours within different tissues, especially in a highly anisotropic structure as the corpus callosum. This fact can provide valuable information about brain structure and different diffusion compartments in clinical DWI.     

Functional MRI changes in the central motor system in myotonic dystrophy type 1

Myotonic dystrophy type 1 (DM1) is a multisystemic disease involving multiple organ systems including central nervous system (CNS) and muscles. Few studies have focused on the central motor system in DM1, pointing to a subclinical abnormality in the CNS. The aim of our study was to investigate patterns of cerebral activation in DM1 during a motor task using functional MRI (fMRI). Fifteen DM1 patients, aged 20 to 59 years, and 15 controls of comparable age were scanned during a self-paced sequential finger-to-thumb opposition task of their dominant right hand. Functional MRI images were analyzed using SPM99. Patients underwent clinical and genetic assessment; all subjects underwent a conventional MR study. Myotonic dystrophy type 1 patients showed greater activation than controls in bilateral sensorimotor areas and inferior parietal lobules, basal ganglia and thalami, in the ipsilateral premotor area, insula and supplementary motor area (corrected P<.05). Analysis of the interaction between disease and age showed that correlation with age was significantly greater in patients than in controls in bilateral sensorimotor areas and in contralateral parietal areas. Other clinical and MR characteristics did not correlate with fMRI. Functional changes in DM1 may represent compensatory mechanisms such as reorganization and redistribution of functional networks to compensate for ultrastructural and neurochemical changes occurring as part of the accelerated aging process.     

Retinotopic mapping with spin echo BOLD at 7T

For blood oxygenation level-dependent (BOLD) functional MRI experiments, contrast-to-noise ratio (CNR) increases with increasing field strength for both gradient echo (GE) and spin echo (SE) BOLD techniques. However, susceptibility artifacts and nonuniform coil sensitivity profiles complicate large field-of-view fMRI experiments (e.g., experiments covering multiple visual areas instead of focusing on a single cortical region). Here, we use SE BOLD to acquire retinotopic mapping data in early visual areas, testing the feasibility of SE BOLD experiments spanning multiple cortical areas at 7T. We also use a recently developed method for normalizing signal intensity in T₁-weighted anatomical images to enable automated segmentation of the cortical gray matter for scans acquired at 7T with either surface or volume coils. We find that the CNR of the 7T GE data (average single-voxel, single-scan stimulus coherence: 0.41) is almost twice that of the 3T GE BOLD data (average coherence: 0.25), with the CNR of the SE BOLD data (average coherence: 0.23) comparable to that of the 3T GE data. Repeated measurements in individual subjects find that maps acquired with 1.8-mm resolution at 3T and 7T with GE BOLD and at 7T with SE BOLD show no systematic differences in either the area or the boundary locations for V1, V2 and V3, demonstrating the feasibility of high-resolution SE BOLD experiments with good sensitivity throughout multiple visual areas.     

Quantitative SENSE-MRSI of the human brain

Purpose

To develop a method for estimating metabolite concentrations using phased-array coils and sensitivity-encoded (SENSE) magnetic resonance spectroscopic images (MRSI) of the human brain.

Materials and Methods

The method is based on the phantom replacement technique and uses receive coil sensitivity maps and body-coil loading factors to account for receive B₁ inhomogeneity and variable coil loading, respectively. Corrections for cerebrospinal fluid content from the MRSI voxel were also applied, and the total protocol scan time was less than 15 min. The method was applied to 10 normal human volunteers using a multislice 2D-MRSI sequence at 3 T, and seven different brain regions were quantified.

Results

N-Acetyl aspartate (NAA) concentrations varied from 9.7 to 14.7 mM, creatine (Cr) varied from 6.6 to 10.6 mM and choline (Cho) varied from 1.6 to 3.0 mM, in good general agreement with prior literature values.

Conclusions

Quantitative SENSE-MRSI of the human brain is routinely possible using an adapted phantom-replacement technique. The method may also be applied to other MRSI techniques, including conventional phase encoding, with phased-array receiver coils, provided that coil sensitivity profiles can be measured.     

Modeling brain tissue volumes over the lifespan: quantitative analysis of postmortem weights and in vivo MR images

Normative measurements of brain gray matter and white matter tissue volumes across the lifespan have not yet been established. The purpose of this article was to use mathematical modeling and analytical functions to demonstrate the growth trajectory of gray matter and white matter from age 0 to age 90. For each gender, brain weight functions were generated by utilizing existing autopsy data from 4400 subjects. Brain gray matter, white matter and lateral ventricular volumes were measured from 39 MR volumes of normal individuals. These were converted to weight by multiplying the tissue volumes by the specific gravity of that tissue. White matter volumes were described by a saturating exponential function, and the gray matter volume function was calculated by subtracting the white matter weight function from the brain weight function. For each gender, equations were generated for white matter and gray matter volumes as a function of age over the lifespan.     

High-Density Optophysiology Platform for Recording Intracellular and Extracellular Signals across the Brain of Free-Moving Animals

Developing a novel tool capable of real-time monitoring and simultaneously quantifying of both intra/extracellular chemical signals across the large-scale brain is the key bottleneck for understanding the interactions between the molecules inside and outside neurons. Here we built up a high-density intra/extracellular optophysiology platform, together with developing two probes for specific recognition of L-cysteine (Cys) and dopamine (DA), for simultaneously quantifying of both intracellular Cys and extracellular DA with high selectivity and accuracy across the brain of freely moving animals, as well as recording electrical signals. Using this powerful tool, it was found that intracellular Cys regulated extracellular DA through inducing the expression of tyrosine hydroxylase in the depressed mice brain. We also established the functional networks of Cys and DA across 32 brain regions in freely moving animals. More importantly, it was discovered that depression reduced the correlations between adjacent brain regions, which was recovered by the treatment of N-acetyl-l-cysteine.