Combined PET/MR: Where Anatomical Imaging Meets Cellular Function.

Recent technological advances in medical imaging have allowed for both sequential and simultaneous acquisition of magnetic resonance imaging (MRI) and positron emission tomography (PET) data. Simultaneous PET/MRI offers distinct advantages by efficiently capturing functional and metabolic processes with co-localized, high-resolution anatomical images while minimizing time and movement. We will describe some of the technical and logistic requirements for optimizing sequential and simultaneous PET/MRI in the preclinical research setting.

NEMA NU 1-2018 performance characterization and Monte Carlo model validation of the Cubresa Spark SiPM-based preclinical SPECT scanner.

Background: The Cubresa Spark is a novel benchtop silicon-photomultiplier (SiPM)-based preclinical SPECT system. SiPMs in SPECT significantly improve resolution and reduce detector size compared to preclinical cameras with photomultiplier tubes requiring highly magnifying collimators. The NEMA NU 1 Standard for Performance Measurements of Gamma Cameras provides methods that can be readily applied or extended to characterize preclinical cameras with minor modifications.

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.

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.

Quantification of Butyrylcholinesterase Activity as a Sensitive and Specific Biomarker of Alzheimer's Disease.

Amyloid-β (Aβ) plaques are a neuropathological hallmark of Alzheimer's disease (AD); however, a significant number of cognitively normal older adults can also have Aβ plaques. Thus, distinguishing AD from cognitively normal individuals with Aβ plaques (NwAβ) based on Aβ plaque detection is challenging. It has been observed that butyrylcholinesterase (BChE) accumulates in plaques preferentially in AD.

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.

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).

Impact of hepatocyte growth factor on skeletal myoblast transplantation late after myocardial infarction.

In clinical studies, skeletal myoblast (SKMB) transplantation late after myocardial infarction (MI) has minimal impact on left ventricular (LV) function. This may be related to our previous observation that the extent of SKMB engraftment is minimal in chronic MI when compared to acute MI, which correlates with decreased hepatocyte growth factor (HGF) expression, an important regulator of SKMB function. Here, we investigated delivery of exogenous HGF as a strategy for augmenting SKMB engraftment late after MI.

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.

Spatial MEG laterality maps for language: clinical applications in epilepsy.

Functional imaging is increasingly being used to provide a noninvasive alternative to intracarotid sodium amobarbitol testing (i.e., the Wada test).