Chemical Exchange Saturation Transfer MRI: What Neuro-Oncology Clinicians Need To Know.

Chemical exchange saturation transfer (CEST) is a relatively novel magnetic resonance imaging (MRI) technique with an image contrast designed for in vivo measurement of certain endogenous molecules with protons that are exchangeable with water protons, such as amide proton transfer commonly used for neuro-oncology applications. Recent technological advances have made it feasible to implement CEST on clinical grade scanners within practical acquisition times, creating new opportunities to integrate CEST in clinical workflow. In addition, the majority of CEST applications used in neuro-oncology are performed without the use gadolinium-based contrast agents which are another appealing feature of this technique.

Early alterations in brain glucose metabolism and vascular function in a transgenic rat model of Alzheimer's disease.

Alteration in brain metabolism predates clinical onset of Alzheimer's Disease (AD). Realizing its potential as an early diagnostic marker, however, requires understanding how early AD metabolic dysregulation manifests on non-invasive brain imaging. We presently utilized magnetic resonance imaging and spectroscopy to map glucose and ketone metabolic profiles and image cerebrovascular function in a rat model of early stage AD - 9-month-old TgF344-AD (TgAD) rats - and their age-matched non-transgenic (nTg) littermates.

Magnetic Targeting of Gadolinium Contrast to Enhance MRI of the Inner Ear in Endolymphatic Hydrops.

Objectives: 1. Determine the feasibility and efficiency of local magnetic targeting delivery of gadolinium (Gad) contrast to the inner ear in rodents. 2.

Saturation Transfer MRI for Detection of Metabolic and Microstructural Impairments Underlying Neurodegeneration in Alzheimer's Disease.

Alzheimer's disease (AD) is one of the most common causes of dementia and difficult to study as the pool of subjects is highly heterogeneous. Saturation transfer (ST) magnetic resonance imaging (MRI) methods are quantitative modalities with potential for non-invasive identification and tracking of various aspects of AD pathology. In this review we cover ST-MRI studies in both humans and animal models of AD over the past 20 years.

Local magnetic delivery of adeno-associated virus AAV2(quad Y-F)-mediated BDNF gene therapy restores hearing after noise injury.

Moderate noise exposure may cause acute loss of cochlear synapses without affecting the cochlear hair cells and hearing threshold; thus, it remains "hidden" to standard clinical tests. This cochlear synaptopathy is one of the main pathologies of noise-induced hearing loss (NIHL). There is no effective treatment for NIHL, mainly because of the lack of a proper drug-delivery technique.

Saturation transfer properties of tumour xenografts derived from prostate cancer cell lines 22Rv1 and DU145.

Histopathology is currently the most reliable tool in assessing the aggressiveness and prognosis of solid tumours. However, developing non-invasive modalities for tumour evaluation remains crucial due to the side effects and complications caused by biopsy procedures. In this study, saturation transfer MRI was used to investigate the microstructural and metabolic properties of tumour xenografts in mice derived from the prostate cancer cell lines 22Rv1 and DU145, which express different aggressiveness.

Dietary supplementation with Lactobacillus rhamnosus JB-1 restores brain neurochemical balance and mitigates the progression of mood disorder in a rat model of chronic unpredictable mild stress.

Major depressive disorder is a stress-related disease associated with brain metabolic dysregulation in the glutamine-glutamate/γ-aminobutyric acid (Gln-Glu/GABA) cycle. Recent studies have demonstrated that microbiome-gut-brain interactions have the potential to influence mental health. The hypothesis of this study was that Lactobacillus rhamnosus JB-1 (LR-JB1™) dietary supplementation has a positive impact on neuro-metabolism which can be quantified in vivo using magnetic resonance spectroscopy (MRS).

An Automated Segmentation Pipeline for Intratumoural Regions in Animal Xenografts Using Machine Learning and Saturation Transfer MRI.

Saturation transfer MRI can be useful in the characterization of different tumour types. It is sensitive to tumour metabolism, microstructure, and microenvironment. This study aimed to use saturation transfer to differentiate between intratumoural regions, demarcate tumour boundaries, and reduce data acquisition times by identifying the imaging scheme with the most impact on segmentation accuracy.

Prolonged inflammation leads to ongoing damage after spinal cord injury.

The pathogenesis of spinal cord injury (SCI) remains poorly understood and treatment remains limited. Emerging evidence indicates that post-SCI inflammation is severe but the role of reactive astrogliosis not well understood given its implication in ongoing inflammation as damaging or neuroprotective. We have completed an extensive systematic study with MRI, histopathology, proteomics and ELISA analyses designed to further define the severe protracted and damaging inflammation after SCI in a rat model.

Investigating the effects of dexamethasone on blood-brain barrier permeability and inflammatory response following focused ultrasound and microbubble exposure.

: Clinical trials are currently underway to test the safety and efficacy of delivering therapeutic agents across the blood-brain barrier (BBB) using focused ultrasound and microbubbles (FUS+MBs). While acoustic feedback control strategies have largely minimized the risk of overt tissue damage, transient induction of inflammatory processes have been observed following sonication in preclinical studies. The goal of this work was to explore the potential of post-sonication dexamethasone (DEX) administration as a means to mitigate treatment risk.

Differentiation of Normal and Radioresistant Prostate Cancer Xenografts Using Magnetization Transfer-Prepared MRI.

The ability of MRI to differentiate between normal and radioresistant cancer was investigated in prostate tumour xenografts in mice. Specifically, the process of magnetization exchange between water and other molecules was studied. It was found that magnetization transfer from semisolid macromolecules (MT) and chemical exchange saturation transfer (CEST) combined were significantly different between groups (p < 0.

Hydrazo-CEST: Hydrazone-Dependent Chemical Exchange Saturation Transfer Magnetic Resonance Imaging Contrast Agents.

The rapid formation of hydrazones under physiological conditions was exploited for the detection of aldehydes through chemical exchange saturation transfer magnetic resonance imaging (CEST-MRI). A metal-free, diamagnetic contrast agent derived from N-amino anthranilic acid was introduced, which selectively "turned-on" upon hydrazone formation through an effect termed Hydrazo-CEST. While the hydrazine form of the probe produced no CEST-MRI signal enhancement, the formation of the aryl hydrazone resulted in >20 % intensity decrease in the bulk water signal through the CEST effect, as measured by 300 MHz H NMR, 3 T and 7 T MRI.

Early regional cuprizone-induced demyelination in a rat model revealed with MRI.

The cuprizone model of demyelination is well established in the mouse as a tool for the study of the mechanisms of both demyelination and remyelination. It is often desirable, however, to have a larger model, such as the rat, especially for imaging-based studies, yet initial work has failed to show demyelination in cuprizone-fed rats. Several recent studies have demonstrated demyelination in the rat, but only in the corpus callosum.

Differences in iron and manganese concentration may confound the measurement of myelin from R1 and R2 relaxation rates in studies of dysmyelination.

A model of dysmyelination, the Long Evans Shaker (les) rat, was used to study the contribution of myelin to MR tissue properties in white matter. A large region of white matter was identified in the deep cerebellum and was used for measurements of the MR relaxation rate constants, R1  = 1/T1 and R2  = 1/T2 , at 7 T. In this study, R1 of the les deep cerebellar white matter was found to be 0.

Closure of the annulus fibrosus of the intervertebral disc using a novel suture application device-in vivo porcine and ex vivo biomechanical evaluation.

Background Context: Defects in the annulus fibrosus (AF) remain a challenge in the surgical treatment of lumbar disc herniations with persistent defects, allowing potential re herniation of nucleus pulposus (NP) tissue. A cervical porcine model was chosen to simulate human lumbar intervertebral disc (IVD).

Purpose: The aim of this study was to determine the technical feasibility of closure of the AF of the IVD using a novel minimally invasive Kerrison-shaped suture application device.

An in vivo model of anti-inflammatory activity of subdural dexamethasone following the spinal cord injury.

Current therapies to limit the neural tissue destruction following the spinal cord injury are not effective. Our recent studies indicate that the injury to the white matter of the spinal cord results in a severe inflammatory response where macrophages phagocytize damaged myelin and the fluid-filled cavity of injury extends in size with concurrent and irreversible destruction of the surrounding neural tissue over several months. We previously established that a high dose of 4mg/rat of dexamethasone administered for 1 week via subdural infusion remarkably lowers the numbers of infiltrating macrophages leaving large amounts of un-phagocytized myelin debris and therefore inhibits the severity of inflammation and related tissue destruction.

Prolonged Subdural Infusion of Kynurenic Acid Is Associated with Dose-Dependent Myelin Damage in the Rat Spinal Cord.

Background: Kynurenic acid (KYNA) is the end stage metabolite of tryptophan produced mainly by astrocytes in the central nervous system (CNS). It has neuroprotective activities but can be elevated in the neuropsychiatric disorders. Toxic effects of KYNA in the CNS are unknown.

Quantitative MRI in a non-surgical model of cervical spinal cord injury.

Quantitative T2 (qT2), diffusion tensor imaging (DTI), and histology were used to investigate a cervical model of spinal cord injury (SCI) in the rat. While quantitative MRI can significantly increase the specificity in the presence of pathology, it must be validated for each type of injury or disease. In the case of traumatic SCI most models are difficult to image, either due to the location of the injury, or as a result of damage to surrounding tissues resulting from invasive surgical procedures.

Gene delivery to the spinal cord using MRI-guided focused ultrasound.

Non-invasive gene delivery across the blood-spinal cord barrier (BSCB) remains a challenge for treatment of spinal cord injury and disease. Here, we demonstrate the use of magnetic resonance image-guided focused ultrasound (MRIgFUS) to mediate non-surgical gene delivery to the spinal cord using self-complementary adeno-associated virus serotype 9 (scAAV9). scAAV9 encoding green fluorescent protein (GFP) was injected intravenously in rats at three dosages: 4 × 10(8), 2 × 10(9) and 7 × 10(9) vector genomes per gram (VG g(-1)).

A non-surgical model of cervical spinal cord injury induced with focused ultrasound and microbubbles.

Background: The most commonly used animal models of spinal cord injury (SCI) involve surgical exposure of the dorsal spinal cord followed by transection, contusion or compression. This high level of invasiveness often requires significant post-operative care and can limit post-operative imaging, as the surgical incision site can interfere with coil placement for magnetic resonance imaging (MRI) during the acute phase of SCI. While these models are considered to be similar to human SCI, they do not occur in a closed vertebral system as do the majority of human injuries.

Effects of diffusion on high-resolution quantitative T2 MRI.

Carr-Purcell-Meiboom-Gill-based sequences are often assumed to be insensitive to diffusion. However, imaging gradients always contribute some degree of diffusion weighting which increases with resolution. This may cause an apparent decrease in T2 when using a multi-echo sequence, such as quantitative T2 (qT2) at high resolution.

Thermally-triggered 'off-on-off' response of gadolinium-hydrogel-lipid hybrid nanoparticles defines a customizable temperature window for non-invasive magnetic resonance imaging thermometry.

For effective and safe thermotherapy, real-time, accurate, three-dimensional tissue thermometry is required. Magnetic resonance imaging (MRI)-based thermometry in combination with current temperature responsive contrast agents only provides an 'off-on' signal at a certain temperature, not indicating temperature increases beyond the desired therapeutic levels. To overcome this limitation, a novel Gd-chelated hydrogel-lipid hybrid nanoparticle (HLN) formulation was developed that provides an 'off-on-off' signal defining a thermometric window for MR thermometry.

Microbubbles loaded with nanoparticles: a route to multiple imaging modalities.

We report a single-step approach to producing small and stable bubbles functionalized with nanoparticles. The strategy includes the following events occurring in sequence: (i) a microfluidic generation of bubbles from a mixture of CO(2) and a minute amount of gases with low solubility in water, in an aqueous solution of a protein, a polysaccharide, and anionic nanoparticles; (ii) rapid dissolution of CO(2) leading to the shrinkage of bubbles and an increase in acidity of the medium in the vicinity of the bubbles; and (iii) co-deposition of the biopolymers and nanoparticles at the bubble-liquid interface. The proposed approach yielded microbubbles with a narrow size distribution, long-term stability, and multiple functions originating from the attachment of metal oxide, metal, or semiconductor nanoparticles onto the bubble surface.

Dynamic contrast-enhanced MRI quantification of synovium microcirculation in experimental arthritis.

Objective: Our objective was to analyze MRI contrast-enhancement patterns in arthritic and nonarthritic knees and the relationship of those patterns with clinical, laboratory, and histologic synovium markers.

Materials And Methods: Dynamic contrast-enhanced MRI was performed in nine arthritic and three nonarthritic knees of juvenile rabbits. A two-compartment pharmacokinetic model of signal intensity-time data was implemented to generate parametric maps of signal slope, maximal percentage of signal change, capillary permeability, leakage space volume, and time-to-peak.

Intraindividual variability of striatal (1)H-MRS brain metabolite measurements at 3 T.

Purpose: To measure possible positional and diurnal physiological effects on brain metabolites in single-voxel proton magnetic resonance spectroscopy ((1)H-MRS) measurements of the right and left striatum.

Methods: (1)H-MRS measurements were performed in 10 healthy adult volunteers using a short echo PRESS sequence (TE=30 ms, TR=3000 ms). Each individual was scanned during both morning and afternoon hours.