No difference in cerebral perfusion between the wild-type and the 5XFAD mouse model of Alzheimer's disease.

Neuroimaging with [2,2-dimethyl-3-[(2R,3E)-3-oxidoiminobutan-2-yl]azanidylpropyl]-[(2R,3E)-3-hydroxyiminobutan-2-yl]azanide;oxo(Tc)technetium-99(3+) ([Tc]HMPAO) single photon emission computed tomography (SPECT) is used in Alzheimer's disease (AD) to evaluate regional cerebral blood flow (rCBF). Hypoperfusion in select temporoparietal regions has been observed in human AD. However, it is unknown whether AD hypoperfusion signatures are also present in the 5XFAD mouse model.

Prospective Evaluation of Virtual MR Elastography With Diffusion-Weighted Imaging in Subjects With Nonalcoholic Fatty Liver Disease.

Background: Non-alcoholic fatty liver disease (NAFLD) is increasingly common worldwide and can lead to the development of cirrhosis, liver failure and cancer. Virtual magnetic resonance elastography (VMRE), which is based on a shifted apparent diffusion coefficient (sADC), is a potential noninvasive method to assess liver fibrosis without the specialized hardware and expertise required to implement traditional MR elastography (MRE). Although hepatic steatosis is known to confound ADC measurements, previous studies using VMRE have not corrected for hepatic fat fraction.

The Developmental Brain Age Is Associated With Adversity, Depression, and Functional Outcomes Among Adolescents.

Background: Most psychiatric disorders emerge in the second decade of life. In the present study, we examined whether environmental adversity, developmental antecedents, major depressive disorder, and functional impairment correlate with deviation from normative brain development in adolescence.

Methods: We trained a brain age prediction model using 189 structural magnetic resonance imaging brain features in 1299 typically developing adolescents (age range 9-19 years, mean = 13.

Combined Transfer Learning and Test-Time Augmentation Improves Convolutional Neural Network-Based Semantic Segmentation of Prostate Cancer from Multi-Parametric MR Images.

Purpose: Multiparametric MRI (mp-MRI) is a widely used tool for diagnosing and staging prostate cancer. The purpose of this study was to evaluate whether transfer learning, unsupervised pre-training and test-time augmentation significantly improved the performance of a convolutional neural network (CNN) for pixel-by-pixel prediction of cancer vs. non-cancer using mp-MRI datasets.

Slow blood-to-brain transport underlies enduring barrier dysfunction in American football players.

Repetitive mild traumatic brain injury in American football players has garnered increasing public attention following reports of chronic traumatic encephalopathy, a progressive tauopathy. While the mechanisms underlying repetitive mild traumatic brain injury-induced neurodegeneration are unknown and antemortem diagnostic tests are not available, neuropathology studies suggest a pathogenic role for microvascular injury, specifically blood-brain barrier dysfunction. Thus, our main objective was to demonstrate the effectiveness of a modified dynamic contrast-enhanced MRI approach we have developed to detect impairments in brain microvascular function.

Reliability of multimodal MRI brain measures in youth at risk for mental illness.

Introduction: A new generation of large-scale studies is using neuroimaging to investigate adolescent brain development across health and disease. However, imaging artifacts such as head motion remain a challenge and may be exacerbated in pediatric clinical samples. In this study, we assessed the scan-rescan reliability of multimodal MRI in a sample of youth enriched for risk of mental illness.

Cell density quantification with TurboSPI: R* mapping with compensation for off-resonance fat modulation.

Objective: Tracking the migration of superparamagnetic iron oxide (SPIO)-labeled immune cells in vivo is valuable for understanding the immunogenic response to cancer and therapies. Quantitative cell tracking using TurboSPI-based R* mapping is a promising development to improve accuracy in longitudinal studies on immune recruitment. However, off-resonance fat signal isochromats lead to modulations in the signal time-course that can be erroneously fit as R* signal decay, overestimating the density of labeled cells, while excluding voxels with fat-typical modulations results in underestimation of cell density in voxels with mixed content.

Psychotic symptoms are associated with lower cortical folding in youth at risk for mental illness.

Background: Cortical folding is essential for healthy brain development. Previous studies have found regional reductions in cortical folding in adult patients with psychotic illness. It is unknown whether these neuroanatomical markers are present in youth with subclinical psychotic symptoms.

Unique depot formed by an oil based vaccine facilitates active antigen uptake and provides effective tumour control.

Background: Oil emulsions are commonly used as vaccine delivery platforms to facilitate slow release of antigen by forming a depot at the injection site. Antigen is trapped in the aqueous phase and as the emulsion degrades in vivo the antigen is passively released. DepoVax™ is a unique oil based delivery system that directly suspends the vaccine components in the oil diluent that forces immune cells to actively take up components from the formulation in the absence of passive release.

Using MRI cell tracking to monitor immune cell recruitment in response to a peptide-based cancer vaccine.

Purpose: MRI cell tracking can be used to monitor immune cells involved in the immunotherapy response, providing insight into the mechanism of action, temporal progression of tumor growth, and individual potency of therapies. To evaluate whether MRI could be used to track immune cell populations in response to immunotherapy, CD8 cytotoxic T cells, CD4 CD25 FoxP3 regulatory T cells, and myeloid-derived suppressor cells were labeled with superparamagnetic iron oxide particles.

Methods: Superparamagnetic iron oxide-labeled cells were injected into mice (one cell type/mouse) implanted with a human papillomavirus-based cervical cancer model.

Targeting butyrylcholinesterase for preclinical single photon emission computed tomography (SPECT) imaging of Alzheimer's disease.

Introduction: Diagnosis of Alzheimer's disease (AD) , by molecular imaging of amyloid or tau, is constrained because similar changes can be found in brains of cognitively normal individuals. Butyrylcholinesterase (BChE), which becomes associated with these structures in AD, could elevate the accuracy of AD diagnosis by focusing on BChE pathology in the cerebral cortex, a region of scant BChE activity in healthy brain.

Methods: -methylpiperidin-4-yl 4-[I]iodobenzoate, a BChE radiotracer, was injected intravenously into B6SJL-Tg(APPSwFlLon, PSEN1∗M146 L∗L286 V) 6799Vas/Mmjax (5XFAD) mice and their wild-type (WT) counterparts for comparative single photon emission computed tomography (SPECT) studies.

Butyrylcholinesterase-knockout reduces fibrillar β-amyloid and conserves FDG retention in 5XFAD mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is the most common neurodegenerative disorder causing dementia. One hallmark of the AD brain is the deposition of β-amyloid (Aβ) plaques. AD is also a state of cholinergic dysfunction and butyrylcholinesterase (BChE) associates with Aβ pathology.

3D single point imaging with compressed sensing provides high temporal resolution R * mapping for in vivo preclinical applications.

Objective: Purely phase-encoded techniques such as single point imaging (SPI) are generally unsuitable for in vivo imaging due to lengthy acquisition times. Reconstruction of highly undersampled data using compressed sensing allows SPI data to be quickly obtained from animal models, enabling applications in preclinical cellular and molecular imaging.

Materials And Methods: TurboSPI is a multi-echo single point technique that acquires hundreds of images with microsecond spacing, enabling high temporal resolution relaxometry of large-R * systems such as iron-loaded cells.

Using lymph node swelling as a potential biomarker for successful vaccination.

There is currently a lack of biomarkers to help properly assess novel immunotherapies at both the preclinical and clinical stages of development. Recent work done by our group indicated significant volume changes in the vaccine draining right lymph node (RLN) volumes of mice that had been vaccinated with DepoVaxTM, a lipid-based vaccine platform that was developed to enhance the potency of peptide-based vaccines. These changes in lymph node (LN) volume were unique to vaccinated mice.

Using MRI to evaluate and predict therapeutic success from depot-based cancer vaccines.

In the preclinical development of immunotherapy candidates, understanding the mechanism of action and determining biomarkers that accurately characterize the induced host immune responses is critical to improving their clinical interpretation. Magnetic resonance imaging (MRI) was used to evaluate in vivo changes in lymph node size in response to a peptide-based cancer vaccine therapy, formulated using DepoVax (DPX). DPX is a novel adjuvant lipid-in-oil-based formulation that facilitates enhanced immune responses by retaining antigens at the injection site for extended latencies, promoting increased potentiation of immune cells.

Fat-suppressed alternating-SSFP for whole-brain fMRI using breath-hold and visual stimulus paradigms.

Purpose: To achieve artifact-suppressed whole-brain pass-band-balanced steady-state free precession functional MRI from a single functional magnetic resonance imaging (fMRI) scan.

Methods: A complete and practical data acquisition sequence for alt-SSFP fMRI was developed. First, multishot flyback-echo-planar imaging (EPI) and echo-time shifting were used to achieve data acquisition that was robust against eddy currents, gradient delays, and ghosting artifacts.

Clearance of depot vaccine SPIO-labeled antigen and substrate visualized using MRI.

Immunotherapies, including peptide-based vaccines, are a growing area of cancer research, and understanding their mechanism of action is crucial for their continued development and clinical application. Exploring the biodistribution of vaccine components may be key to understanding this action. This work used magnetic resonance imaging (MRI) to characterize the in vivo biodistribution of the antigen and oil substrate of the vaccine delivery system known as DepoVax(TM).

Pre-clinical study of drug combinations that reduce breast cancer burden due to aberrant mTOR and metabolism promoted by LKB1 loss.

Cancer therapies that simultaneously target activated mammalian target of rapamycin (mTOR) and cell metabolism are urgently needed. The goal of our study was to identify therapies that effectively inhibited both mTOR activity and cancer cell metabolism in primary tumors in vivo. Using our mouse model of spontaneous breast cancer promoted by loss of LKB1 expression in an ErbB2 activated model; referred to as LKB1-/-NIC mice, we evaluated the effect of novel therapies in vivo on primary tumors.

Quantification of superparamagnetic iron oxide using inversion recovery balanced steady-state free precession.

Cellular and molecular MRI trafficking studies using superparamagnetic iron oxide (SPIO) have greatly improved non-invasive investigations of disease progression and drug efficacy, but thus far, these studies have largely been restricted to qualitative assessment of hypo- or hyperintense areas near SPIO. In this work, SPIO quantification using inversion recovery balanced steady-state free precession (IR-bSSFP) was demonstrated at 3T by extracting R2 values from a monoexponential model (P. Schmitt et al.

In vivo detection of human TRPV6-rich tumors with anti-cancer peptides derived from soricidin.

Soricidin is a 54-amino acid peptide found in the paralytic venom of the northern short-tailed shrew (Blarina brevicauda) and has been found to inhibit the transient receptor potential of vallinoid type 6 (TRPV6) calcium channels. We report that two shorter peptides, SOR-C13 and SOR-C27, derived from the C-terminus of soricidin, are high-affinity antagonists of human TRPV6 channels that are up-regulated in a number of cancers. Herein, we report molecular imaging methods that demonstrate the in vivo diagnostic potential of SOR-C13 and SOR-C27 to target tumor sites in mice bearing ovarian or prostate tumors.

Signal displacement in spiral-in acquisitions: simulations and implications for imaging in SFG regions.

Susceptibility field gradients (SFGs) cause problems for functional magnetic resonance imaging (fMRI) in regions like the orbital frontal lobes, leading to signal loss and image artifacts (signal displacement and "pile-up"). Pulse sequences with spiral-in k-space trajectories are often used when acquiring fMRI in SFG regions such as inferior/medial temporal cortex because it is believed that they have improved signal recovery and decreased signal displacement properties. Previously postulated theories explain differing reasons why spiral-in appears to perform better than spiral-out; however it is clear that multiple mechanisms are occurring in parallel.

Quantification of superparamagnetic iron oxide with large dynamic range using TurboSPI.

This work proposes the use of TurboSPI, a multi-echo single point imaging sequence, for the quantification of labeled cells containing moderate to high concentrations of iron oxide contrast agent. At each k-space location, TurboSPI acquires several hundred time points during a spin echo, permitting reliable relaxation rate mapping of large-R(2)(∗) materials. An automatic calibration routine optimizes image quality by promoting coherent alignment of spin and stimulated echoes throughout the multi-echo train, and this calibration is sufficiently robust for in vivo applications.

Confirming white matter fMRI activation in the corpus callosum: co-localization with DTI tractography.

Recently, functional magnetic resonance imaging (fMRI) activation has been detected in white matter, despite the widely-held belief that fMRI activation is restricted to gray matter. The objective of the current study was to determine whether the regions of white matter fMRI activation were structurally connected to the functional network in gray matter. To do this, we used fMRI-guided tractography to evaluate whether tracts connecting regions of gray matter fMRI activation were co-localized with white matter fMRI activation.

Asymmetric spin-echo (ASE) spiral improves BOLD fMRI in inhomogeneous regions.

Functional MRI (fMRI) is of limited use in areas such as the orbitofrontal and inferior temporal lobes due to the presence of local susceptibility-induced field gradients (SFGs), which result in severe image artifacts. Several techniques have been developed to reduce these artifacts, the most common being the dual-echo spiral sequences (spiral-in/out and spiral-in/in). In this study, a new multiple spiral acquisition technique was developed, in which the later spiral acquisitions are acquired asymmetrically with the peak of a spin-echo causing increased R(2)-weighting but matched R(2)'-weighting.