two-photon-intravital-microscopy-of-glioblastoma-in-a-murine-model

Two-Photon Intravital Microscopy of Glioblastoma in a Murine Model

The delivery of intravenously administered cancer therapeutics to brain tumors is limited by the blood-brain barrier. A method to directly image the ...

Stanford University School of Medicine

To describe approaches for determining optimal spatial and temporal resolutions for the proton resonance frequency shift method of quantitative magnetic resonance temperature imaging (MRTI) guidance of transurethral ultrasonic prostate ablation.

Effects of spatial and temporal resolution for MR image-guided thermal ablation of prostate with transurethral ultrasound.

A restricted field of view (rFOV) approach for imaging a dynamic time series of volumes of limited spatial extent within a larger subject is described. The shorter readout with rFOV-MRI can be exploited to either limit image artifacts or increase spatial resolution. To accomplish rFOV imaging of a multislice volume for a dynamic series, an outer volume suppression (OVS) preparation that saturates signal external to a cylinder through the subject is followed by slice-selective excitation and a spiral readout. The pass- and stopband efficiencies of the OVS in an agar gel phantom were 97% (+/-1.5%) and 3% (+/-1%), respectively. Profiles of the temporal signal-to-noise ratio (SNR) were measured in a phantom and an adult brain. The rFOV sequence reduced distortions from off-resonance signal and T2*-induced blurring compared to a conventional sequence. Sequence utility is demonstrated for high-resolution rFOV functional MRI (fMRI) in the visual cortex. The rFOV sequence may prove to be useful for other multislice dynamic and high-resolution imaging applications.

Restricted field of view magnetic resonance imaging of a dynamic time series.

Listeriosis is one of the most lethal bacterial diseases for fetuses and infants. However, pregnant women who get infected with Listeria may experience only mild symptoms, making the diagnosis difficult, even when the fetus is fatally infected.

Infection of pregnant mice with Listeria monocytogenes induces fetal bradycardia.

Macrophage infiltration is a prominent feature of abdominal aortic aneurysm (AAA) progression. We used a combined imaging approach with bioluminescence (BLI) and magnetic resonance imaging (MRI) to study macrophage homing and accumulation in experimental AAA disease. Murine AAAs were created via intra-aortic infusion of porcine pancreatic elastase. Mice were imaged over 14 days after injection of prepared peritoneal macrophages. For BLI, macrophages were from transgenic mice expressing luciferase. For MRI, macrophages were labeled with iron oxide particles. Macrophage accumulation during aneurysm progression was observed by in situ BLI and by in vivo 7T MRI. Mice were sacrificed after imaging for histologic analysis. In situ BLI (n  =  32) demonstrated high signal in the AAA by days 7 and 14, which correlated significantly with macrophage number and aortic diameter. In vivo 7T MRI (n  =  13) at day 14 demonstrated T₂* signal loss in the AAA and not in sham mice. Immunohistochemistry and Prussian blue staining confirmed the presence of injected macrophages in the AAA. BLI and MRI provide complementary approaches to track macrophage homing and accumulation in experimental AAAs. Similar dual imaging strategies may aid the study of AAA biology and the evaluation of novel therapies.

Bioluminescence and magnetic resonance imaging of macrophage homing to experimental abdominal aortic aneurysms.

To develop a clinically applicable imaging technique for monitoring differential migration of macrophages into viable and apoptotic matrix-associated stem cell implants (MASIs) in arthritic knee joints.

Intravenous ferumoxytol allows noninvasive MR imaging monitoring of macrophage migration into stem cell transplants.

The purpose of this study is to evaluate the 18 kDa translocator protein (TSPO) radioligand [(18)F]N-fluoroacetyl-N-(2,5-dimethoxybenzyl)-2-phenoxyaniline ([(18)F]PBR06) as a positron emission tomography (PET) imaging biomarker of stroke-induced neuroinflammation in a rodent model.

PET imaging of stroke-induced neuroinflammation in mice using [18F]PBR06.

To evaluate whether ultrasmall superparamagnetic iron oxide nanoparticle (USPIO)-enhanced magnetic resonance imaging (MRI) can detect allograft rejection in pediatric kidney transplant patients.

Ferumoxytol Is Not Retained in Kidney Allografts in Patients Undergoing Acute Rejection.

 Tumor-associated macrophages (TAMs) in malignant tumors have been linked to tumor aggressiveness and represent a new target for cancer immunotherapy. As new TAM-targeted immunotherapies are entering clinical trials, it is important to detect and quantify TAM with noninvasive imaging techniques. The purpose of this study was to determine if ferumoxytol-enhanced MRI can detect TAM in lymphomas and bone sarcomas of pediatric patients and young adults. In a , Institutional Review Board-approved prospective clinical trial, 25 pediatric and young adult patients with lymphoma or bone sarcoma underwent ferumoxytol-enhanced MRI. To confirm ferumoxytol enhancement, five pilot patients (two lymphoma and three bone sarcoma) underwent pre- and postcontrast MRI. Subsequently, 20 patients (10 lymphoma and 10 bone sarcoma) underwent ferumoxytol-enhanced MRI 24 to 48 hours after i.v. injection, followed by tumor biopsy/resection and macrophage staining. To determine if ferumoxytol-MRI can differentiate tumors with different TAM content, we compared T2* relaxation times of lymphomas and bone sarcomas. Tumor T2* values of 20 patients were correlated with CD68 and CD163 TAM quantities on histopathology. Significant ferumoxytol tumor enhancement was noted on postcontrast scans compared with precontrast scans ( = 0.036). Bone sarcomas and lymphomas demonstrated significantly different MRI enhancement and TAM density ( < 0.05). Within each tumor group, T2* signal enhancement on MR images correlated significantly with the density of CD68 and CD163 TAM ( < 0.05). Ferumoxytol-enhanced MRI is immediately clinically applicable and could be used to stratify patients with TAM-rich tumors to immune-targeted therapies and to monitor tumor response to these therapies. .

Magnetic Resonance Imaging of Tumor-Associated Macrophages: Clinical Translation.

A novel clinically translatable iron oxide nanoparticle (IOP) is currently being tested in phase 2 clinical trials as a magnetic resonance imaging (MRI) contrast agent for hepatocellular carcinoma diagnosis. The purpose of our study is to evaluate if this IOP can detect activation of tumor-associated macrophages (TAMs) due to CD47 mAb-targeted immunotherapy in 2 mouse models of osteosarcoma.

Novel Clinically Translatable Iron Oxide Nanoparticle for Monitoring Anti-CD47 Cancer Immunotherapy.

We sought to create and characterize a mouse model of the inflammatory, cerebral demyelinating phenotype of X-linked adrenoleukodystrophy (ALD) that would facilitate the study of disease pathogenesis and therapy development. We also sought to cross-validate potential therapeutic targets such as fibrin, oxidative stress, and the NLRP3 inflammasome, in post-mortem human and murine brain tissues.

Article	Year
Effects of spatial and temporal resolution for MR image-guided thermal ablation of prostate with transurethral ultrasound. Journal of magnetic resonance imaging : JMRI\| PubMed ID: 15971190	2005
Restricted field of view magnetic resonance imaging of a dynamic time series. Magnetic resonance in medicine\| PubMed ID: 17260360	2007
Infection of pregnant mice with Listeria monocytogenes induces fetal bradycardia. Pediatric research\| PubMed ID: 22314663	2012
Bioluminescence and magnetic resonance imaging of macrophage homing to experimental abdominal aortic aneurysms. Molecular imaging\| PubMed ID: 22469240	2012
Intravenous ferumoxytol allows noninvasive MR imaging monitoring of macrophage migration into stem cell transplants. Radiology\| PubMed ID: 22820731	2012
PET imaging of stroke-induced neuroinflammation in mice using [18F]PBR06. Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging\| PubMed ID: 23836504	2014
Ferumoxytol Is Not Retained in Kidney Allografts in Patients Undergoing Acute Rejection. Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging\| PubMed ID: 28411307	2017
Magnetic Resonance Imaging of Tumor-Associated Macrophages: Clinical Translation. Clinical cancer research : an official journal of the American Association for Cancer Research\| PubMed ID: 29764855	2018
Novel Clinically Translatable Iron Oxide Nanoparticle for Monitoring Anti-CD47 Cancer Immunotherapy. Investigative radiology\| PubMed ID: 37812494	2023
A novel mouse model of cerebral adrenoleukodystrophy highlights NLRP3 activity in lesion pathogenesis. bioRxiv : the preprint server for biology\| PubMed ID: 37986739	2023

Laura Pisani

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