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-β 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-β clearance, may be impaired in CAA.

Computational peptide discovery with a genetic programming approach.

The development of peptides for therapeutic targets or biomarkers for disease diagnosis is a challenging task in protein engineering. Current approaches are tedious, often time-consuming and require complex laboratory data due to the vast search spaces that need to be considered. In silico methods can accelerate research and substantially reduce costs.

Dynamic and rapid deep synthesis of chemical exchange saturation transfer and semisolid magnetization transfer MRI signals.

Model-driven analysis of biophysical phenomena is gaining increased attention and utility for medical imaging applications. In magnetic resonance imaging (MRI), the availability of well-established models for describing the relations between the nuclear magnetization, tissue properties, and the externally applied magnetic fields has enabled the prediction of image contrast and served as a powerful tool for designing the imaging protocols that are now routinely used in the clinic. Recently, various advanced imaging techniques have relied on these models for image reconstruction, quantitative tissue parameter extraction, and automatic optimization of acquisition protocols.

Computational Peptide Discovery with a Genetic Programming Approach.

Background: The development of peptides for therapeutic targets or biomarkers for disease diagnosis is a challenging task in protein engineering. Current approaches are tedious, often time-consuming and require complex laboratory data due to the vast search space. methods can accelerate research and substantially reduce costs.

Development of a synthetic biosensor for chemical exchange MRI utilizing in silico optimized peptides.

Chemical exchange saturation transfer (CEST) MRI has been identified as a novel alternative to classical diagnostic imaging. Over the last several decades, many studies have been conducted to determine possible CEST agents, such as endogenously expressed compounds or proteins, that can be utilized to produce contrast with minimally invasive procedures and reduced or non-existent levels of toxicity. In recent years there has been an increased interest in the generation of genetically engineered CEST contrast agents, typically based on existing proteins with CEST contrast or modified to produce CEST contrast.

Psychological support for chronic conditions.

Purpose Of Review: Haematological conditions are varied, and every condition presents unique psychosocial challenges to patients and their families. There is a growing body of evidence about high levels of psychological distress, negative impact on outcomes and evidence-based treatments, yet service provision is patchy and demand far exceeds supply.

Recent Findings: This article focuses on the major subspecialty areas and associated neuropsychiatric comorbidities - haematological malignancies, issues related to stem cell transplants, haemoglobinopathies and haemophilia.

Development of a Synthetic Biosensor for Chemical Exchange MRI Utilizing Optimized Peptides.

Chemical Exchange Saturation Transfer (CEST) magnetic resonance imaging (MRI) has been identified as a novel alternative to classical diagnostic imaging. Over the last several decades, many studies have been conducted to determine possible CEST agents, such as endogenously expressed compounds or proteins, that can be utilized to produce contrast with minimally invasive procedures and reduced or non-existent levels of toxicity. In recent years there has been an increased interest in the generation of genetically engineered CEST contrast agents, typically based on existing proteins with CEST contrast or modified to produce CEST contrast.

A Genetic Programming Approach to Engineering MRI Reporter Genes.

Here we develop a mechanism of protein optimization using a computational approach known as "genetic programming". We developed an algorithm called Protein Optimization Engineering Tool (POET). Starting from a small library of literature values, the use of this tool allowed us to develop proteins that produce four times more MRI contrast than what was previously state-of-the-art.

Oncolytic HSV1 targets different growth phases of breast cancer leptomeningeal metastases.

Leptomeningeal metastasis is a fatal complication of breast cancer which results when cancer cells seed in the meninges. Currently there is no cure, limiting survival to less than four months. Treatment options are palliative.

BAP1 is a novel regulator of HIF-1α.

is a powerful tumor suppressor gene characterized by haplo insufficiency. Individuals carrying germline mutations often develop mesothelioma, an aggressive malignancy of the serosal layers covering the lungs, pericardium, and abdominal cavity. Intriguingly, mesotheliomas developing in carriers of germline mutations are less aggressive, and these patients have significantly improved survival.

Accelerated and quantitative three-dimensional molecular MRI using a generative adversarial network.

Purpose: To substantially shorten the acquisition time required for quantitative three-dimensional (3D) chemical exchange saturation transfer (CEST) and semisolid magnetization transfer (MT) imaging and allow for rapid chemical exchange parameter map reconstruction.

Methods: Three-dimensional CEST and MT magnetic resonance fingerprinting (MRF) datasets of L-arginine phantoms, whole-brains, and calf muscles from healthy volunteers, cancer patients, and cardiac patients were acquired using 3T clinical scanners at three different sites, using three different scanner models and coils. A saturation transfer-oriented generative adversarial network (GAN-ST) supervised framework was then designed and trained to learn the mapping from a reduced input data space to the quantitative exchange parameter space, while preserving perceptual and quantitative content.

CEST MR fingerprinting (CEST-MRF) for brain tumor quantification using EPI readout and deep learning reconstruction.

Purpose: To develop a clinical CEST MR fingerprinting (CEST-MRF) method for brain tumor quantification using EPI acquisition and deep learning reconstruction.

Methods: A CEST-MRF pulse sequence originally designed for animal imaging was modified to conform to hardware limits on clinical scanners while keeping scan time under 2 min. Quantitative MRF reconstruction was performed using a deep reconstruction network (DRONE) to yield the water relaxation and chemical exchange parameters.

Magnetic resonance imaging of cardiac metabolism in heart failure: how far have we come?

As one of the highest energy consumer organs in the body, the heart requires tremendous amount of adenosine triphosphate (ATP) to maintain its continuous mechanical work. Fatty acids, glucose, and ketone bodies are the primary fuel source of the heart to generate ATP with perturbations in ATP generation possibly leading to contractile dysfunction. Cardiac metabolic imaging with magnetic resonance imaging (MRI) plays a crucial role in understanding the dynamic metabolic changes occurring in the failing heart, where the cardiac metabolism is deranged.

Total ice content and lipid saturation determine adipose tissue cryolipolysis by injection of ice-slurry.

Objectives: Cryolipolysis uses tissue cooling to solidify lipids, preferentially damaging lipid-rich cells. Topical cooling is popular for the reduction of local subcutaneous fat. Injection of biocompatible ice-slurry is a recently introduced alternative.

MR fingerprinting for semisolid magnetization transfer and chemical exchange saturation transfer quantification.

Chemical exchange saturation transfer (CEST) MRI has positioned itself as a promising contrast mechanism, capable of providing molecular information at sufficient resolution and amplified sensitivity. However, it has not yet become a routinely employed clinical technique, due to a variety of confounding factors affecting its contrast-weighted image interpretation and the inherently long scan time. CEST MR fingerprinting (MRF) is a novel approach for addressing these challenges, allowing simultaneous quantitation of several proton exchange parameters using rapid acquisition schemes.

An end-to-end AI-based framework for automated discovery of rapid CEST/MT MRI acquisition protocols and molecular parameter quantification (AutoCEST).

Purpose: To develop an automated machine-learning-based method for the discovery of rapid and quantitative chemical exchange saturation transfer (CEST) MR fingerprinting acquisition and reconstruction protocols.

Methods: An MR physics-governed AI system was trained to generate optimized acquisition schedules and the corresponding quantitative reconstruction neural network. The system (termed AutoCEST) is composed of a CEST saturation block, a spin dynamics module, and a deep reconstruction network, all differentiable and jointly connected.

Quantitative imaging of apoptosis following oncolytic virotherapy by magnetic resonance fingerprinting aided by deep learning.

Non-invasive imaging methods for detecting intratumoural viral spread and host responses to oncolytic virotherapy are either slow, lack specificity or require the use of radioactive or metal-based contrast agents. Here we show that in mice with glioblastoma multiforme, the early apoptotic responses to oncolytic virotherapy (characterized by decreased cytosolic pH and reduced protein synthesis) can be rapidly detected via chemical-exchange-saturation-transfer magnetic resonance fingerprinting (CEST-MRF) aided by deep learning. By leveraging a deep neural network trained with simulated magnetic resonance fingerprints, CEST-MRF can generate quantitative maps of intratumoural pH and of protein and lipid concentrations by selectively labelling the exchangeable amide protons of endogenous proteins and the exchangeable macromolecule protons of lipids, without requiring exogenous contrast agents.

Complement in ischaemia-reperfusion injury and transplantation.

Until recently, the only known condition in which complement could mediate transplant injury was the rare occurrence of antibody-mediated rejection, in which the original concept of antibody immunity against the transplant was supported by complementary proteins present in the serum. This has changed within the last two decades because of evidence that the processes of ischaemia-reperfusion injury followed by T cell-mediated rejection are also critically dependent on components generated by the complement system. We now have a clearer understanding of the complement triggers and effectors that mediate injury, and a detailed map of their local sites of production and activation in the kidney.

Tracking the Migration of Injectable Microdevices in the Rodent Brain Using a 9.4T Magnetic Resonance Imaging Scanner.

Wirelessly powered microdevices are being miniaturized to improve safety, longevity, and spatial resolution in a wide range of biomedical applications. Some wireless microdevices have reached a point where they can be injected whole into the central nervous system. However, the state-of-the-art floating microdevices have not yet been tested in chronic brain applications, and there is a growing concern that the implants might migrate through neural tissue over time.

Localized Darier disease: three cases of Type 1 segmental mosaicism.

Darier disease (DD) is an autosomal dominant acantholytic dermatosis with an estimated prevalence of 1 in 30 000-100 000. A localized form of DD was first described by Kreibich in 1906 and is thought to account for 10% of all cases. A number of clinical variants have been reported including: unilateral, linear, segmental or zosteriform DD.

Pulseq-CEST: Towards multi-site multi-vendor compatibility and reproducibility of CEST experiments using an open-source sequence standard.

Purpose: As the field of CEST grows, various novel preparation periods using different parameters are being introduced. At the same time, large, multisite clinical studies require clearly defined protocols, especially across different vendors. Here, we propose a CEST definition standard using the open Pulseq format for a shareable, simple, and exact definition of CEST protocols.