Non-invasive MRI measurements of age-dependent in vivo human glymphatic exchange using magnetization transfer spin labeling.

Background: The water exchange between brain parenchyma and cerebrospinal fluid (CSF) is considered to be responsible for glymphatic clearance of solutes and metabolic wastes from the brain, including amyloid-β, a biomarker in neurodegeneration. Despite the potential significance, no noninvasive technique for in vivo measurement of parenchyma-CSF water exchange has been demonstrated in humans, capable of investigating age-related changes in glymphatic clearance.

Purpose: To demonstrate a noninvasive, translatable MRI technique capable of measuring glymphatic water exchange in humans and to apply this technique to examine age-related changes in the glymphatic exchange measures in healthy subjects.

Volumetric T -weighted spin echo imaging with improved SNR using localized quadratic encoding and a spiral readout trajectory.

Purpose: To demonstrate T -weighted (single-echo) spin-echo (SE) imaging with near-optimal acquisition efficiency by applying SNR-efficient RF slice encoding and spiral readout.

Methods: A quadratic-phase (frequency swept) excitation RF pulse replaced the conventional excitation in T -weighted SE sequence to excite a thick slab that is internally spatially encoded by a variable phase along the slice direction. Highly overlapping slabs centered at every desired slice location were acquired in multiple passes, such that the entire imaging volume was excited by contiguous slabs in any given pass.

Tailoring renal-clearable zwitterionic cyclodextrin for colorectal cancer-selective drug delivery.

Although cyclodextrin-based renal-clearable nanocarriers have a high potential for clinical translation in targeted cancer therapy, their designs remain to be optimized for tumour retention. Here we report on the design of a tailored structure for renal-clearable zwitterionic cyclodextrin for colorectal cancer-selective drug delivery. Twenty cyclodextrin derivatives with different charged moieties and spacers are synthesized and screened for colloidal stability.

Accelerated 4D-flow MRI with 3-point encoding enabled by machine learning.

Purpose: To investigate the acceleration of 4D-flow MRI using a convolutional neural network (CNN) that produces three directional velocities from three flow encodings, without requiring a fourth reference scan measuring background phase.

Methods: A fully 3D CNN using a U-net architecture was trained in a block-wise fashion to take complex images from three flow encodings and to produce three real-valued images for each velocity component. Using neurovascular 4D-flow scans (n = 144), the CNN was trained to predict velocities computed from four flow encodings by standard reconstruction including correction for residual background phase offsets.

Simultaneous 3D-TOF angiography and 4D-flow MRI with enhanced flow signal using multiple overlapping thin slab acquisition and magnetization transfer.

Purpose: To investigate the fusion of 3D time-of-flight principles into 4D-flow MRI to enhance vessel contrast and signal without an exogenous contrast agent, enabling simultaneous in-flow based angiograms.

Methods: A 4D-flow MRI technique was developed consisting of multiple overlapping slabs with intermittent magnetization transfer preparation. The scan time penalty associated with multiple slab acquisitions was mitigated by using undersampled distributed spiral trajectories and compressed sensing reconstruction.

Composite MRA: statistical approach to generate an MR angiogram from multiple contrasts.

Purpose: To develop a method to use information from multiple MRI contrasts to produce a composite angiogram with reduced sequence-specific artifacts and improved vessel depiction.

Methods: Bayesian posterior vessel probability was determined as a function of black blood (BB), contrast enhanced angiography (CE-MRA), and phase-contrast MRA (PC-MRA) intensities from training subjects (N = 4). To generate composite angiogram in evaluation subjects (N = 12), the voxel-wise vessel probabilities were weighted with a confidence measure and combined as a weighted product to yield angiogram intensity.

Simultaneous multicolor imaging of biological structures with fluorescence photoactivation localization microscopy.

Localization-based super resolution microscopy can be applied to obtain a spatial map (image) of the distribution of individual fluorescently labeled single molecules within a sample with a spatial resolution of tens of nanometers. Using either photoactivatable (PAFP) or photoswitchable (PSFP) fluorescent proteins fused to proteins of interest, or organic dyes conjugated to antibodies or other molecules of interest, fluorescence photoactivation localization microscopy (FPALM) can simultaneously image multiple species of molecules within single cells. By using the following approach, populations of large numbers (thousands to hundreds of thousands) of individual molecules are imaged in single cells and localized with a precision of ~10-30 nm.

Bleed-through correction for rendering and correlation analysis in multi-colour localization microscopy.

Multi-colour localization microscopy has enabled sub-diffraction studies of colocalization between multiple biological species and quantification of their correlation at length scales previously inaccessible with conventional fluorescence microscopy. However, bleed-through, or misidentification of probe species, creates false colocalization and artificially increases certain types of correlation between two imaged species, affecting the reliability of information provided by colocalization and quantified correlation. Despite the potential risk of these artefacts of bleed-through, neither the effect of bleed-through on correlation nor methods of its correction in correlation analyses has been systematically studied at typical rates of bleed-through reported to affect multi-colour imaging.

Actin mediates the nanoscale membrane organization of the clustered membrane protein influenza hemagglutinin.

The influenza viral membrane protein hemagglutinin (HA) is required at high concentrations on virion and host-cell membranes for infectivity. Because the role of actin in membrane organization is not completely understood, we quantified the relationship between HA and host-cell actin at the nanoscale. Results obtained using superresolution fluorescence photoactivation localization microscopy (FPALM) in nonpolarized cells show that HA clusters colocalize with actin-rich membrane regions (ARMRs).