Harnessing multimodality to enhance quantification and reproducibility of in vivo molecular imaging data

Background: Positron-emission-tomography (PET) using 18F labeled florbetaben allows noninvasive in vivo-assessment of amyloid-beta (Aβ), a pathological hallmark of Alzheimer’s disease (AD). In preclinical research, [18F]-florbetaben-PET has already been used to test the amyloid-lowering potential of new drugs, both in humans and in transgenic models of cerebral amyloidosis. The aim of this study was to characterize the spatial pattern of cerebral uptake of [18F]-florbetaben in the APPswe/ PS1dE9 mouse model of AD in comparison to histologically determined number and size of cerebral Aβ plaques. Methods: Both, APPswe/PS1dE9 and wild type mice at an age of 12 months were investigated by smallanimal PET/CT after intravenous injection of [18F]-florbetaben. High-resolution magnetic resonance imaging data were used for quantification of the PET data by volume of interest analysis. The standardized uptake values (SUVs) of [18F]-florbetaben in vivo as well as post mortem cerebral Aβ plaque load in cortex, hippocampus and cerebellum were analyzed. Results: Visual inspection and SUVs revealed an increased cerebral uptake of [18F]-florbetaben in APPswe/ PS1dE9 mice compared with wild type mice especially in the cortex, the hippocampus and the cerebellum. However, SUV ratios (SUVRs) relative to cerebellum revealed only significant differences in the hippocampus between the APPswe/PS1dE9 and wild type mice but not in cortex; this differential effect may reflect the lower plaque area in the cortex than in the hippocampus as found in the histological analysis. Conclusion: The findings suggest that histopathological characteristics of Aβ plaque size and spatial distribution can be depicted in vivo using [18F]-florbetaben in the APPswe/PS1dE9 mouse model.

Download Full-text

Targeting the Extracellular Matrix in Abdominal Aortic Aneurysms Using Molecular Imaging Insights

International Journal of Molecular Sciences ◽

10.3390/ijms22052685 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2685

Author(s):

Lisa Adams ◽

Julia Brangsch ◽

Bernd Hamm ◽

Marcus R. Makowski ◽

Sarah Keller

Keyword(s):

Extracellular Matrix ◽

Molecular Imaging ◽

Molecular Targets ◽

Abdominal Aortic Aneurysms ◽

Aortic Aneurysms ◽

Type I ◽

Target Tissue ◽

Pharmacologic Treatment ◽

Abdominal Aortic

This review outlines recent preclinical and clinical advances in molecular imaging of abdominal aortic aneurysms (AAA) with a focus on molecular magnetic resonance imaging (MRI) of the extracellular matrix (ECM). In addition, developments in pharmacologic treatment of AAA targeting the ECM will be discussed and results from animal studies will be contrasted with clinical trials. Abdominal aortic aneurysm (AAA) is an often fatal disease without non-invasive pharmacologic treatment options. The ECM, with collagen type I and elastin as major components, is the key structural component of the aortic wall and is recognized as a target tissue for both initiation and the progression of AAA. Molecular imaging allows in vivo measurement and characterization of biological processes at the cellular and molecular level and sets forth to visualize molecular abnormalities at an early stage of disease, facilitating novel diagnostic and therapeutic pathways. By providing surrogate criteria for the in vivo evaluation of the effects of pharmacological therapies, molecular imaging techniques targeting the ECM can facilitate pharmacological drug development. In addition, molecular targets can also be used in theranostic approaches that have the potential for timely diagnosis and concurrent medical therapy. Recent successes in preclinical studies suggest future opportunities for clinical translation. However, further clinical studies are needed to validate the most promising molecular targets for human application.

Download Full-text

Will we successfully avoid the garbage in garbage out problem in imaging data mining? An overview on current concepts and future directions in molecular imaging

Methods ◽

10.1016/j.ymeth.2021.02.011 ◽

2021 ◽

Vol 188 ◽

pp. 1-3

Author(s):

F.M. Mottaghy ◽

F. Hertel ◽

M. Beheshti

Keyword(s):

Data Mining ◽

Molecular Imaging ◽

Imaging Data ◽

Future Directions

Download Full-text

Multi-Modal Multi-Spectral Intravital Microscopic Imaging of Signaling Dynamics in Real-Time during Tumor–Immune Interactions

Cells ◽

10.3390/cells10030499 ◽

2021 ◽

Vol 10 (3) ◽

pp. 499

Author(s):

Tracy W. Liu ◽

Seth T. Gammon ◽

David Piwnica-Worms

Keyword(s):

Molecular Imaging ◽

Single Cell ◽

Real Time ◽

Bioluminescence Imaging ◽

Emission Spectra ◽

Ccd Camera ◽

Microscopic Imaging ◽

Signaling Dynamics ◽

Window Chamber

Intravital microscopic imaging (IVM) allows for the study of interactions between immune cells and tumor cells in a dynamic, physiologically relevant system in vivo. Current IVM strategies primarily use fluorescence imaging; however, with the advances in bioluminescence imaging and the development of new bioluminescent reporters with expanded emission spectra, the applications for bioluminescence are extending to single cell imaging. Herein, we describe a molecular imaging window chamber platform that uniquely combines both bioluminescent and fluorescent genetically encoded reporters, as well as exogenous reporters, providing a powerful multi-plex strategy to study molecular and cellular processes in real-time in intact living systems at single cell resolution all in one system. We demonstrate that our molecular imaging window chamber platform is capable of imaging signaling dynamics in real-time at cellular resolution during tumor progression. Importantly, we expand the utility of IVM by modifying an off-the-shelf commercial system with the addition of bioluminescence imaging achieved by the addition of a CCD camera and demonstrate high quality imaging within the reaches of any biology laboratory.

Download Full-text

The relationship between hippocampal-dependent task performance and hippocampal grey matter myelination and iron content

Brain and Neuroscience Advances ◽

10.1177/23982128211011923 ◽

2021 ◽

Vol 5 ◽

pp. 239821282110119

Author(s):

Ian A. Clark ◽

Martina F. Callaghan ◽

Nikolaus Weiskopf ◽

Eleanor A. Maguire

Keyword(s):

Individual Differences ◽

Autobiographical Memory ◽

Task Performance ◽

Iron Content ◽

Grey Matter ◽

Cognitive Task ◽

Spatial Navigation ◽

Imaging Data ◽

Future Thinking

Individual differences in scene imagination, autobiographical memory recall, future thinking and spatial navigation have long been linked with hippocampal structure in healthy people, although evidence for such relationships is, in fact, mixed. Extant studies have predominantly concentrated on hippocampal volume. However, it is now possible to use quantitative neuroimaging techniques to model different properties of tissue microstructure in vivo such as myelination and iron. Previous work has linked such measures with cognitive task performance, particularly in older adults. Here we investigated whether performance on scene imagination, autobiographical memory, future thinking and spatial navigation tasks was associated with hippocampal grey matter myelination or iron content in young, healthy adult participants. Magnetic resonance imaging data were collected using a multi-parameter mapping protocol (0.8 mm isotropic voxels) from a large sample of 217 people with widely-varying cognitive task scores. We found little evidence that hippocampal grey matter myelination or iron content were related to task performance. This was the case using different analysis methods (voxel-based quantification, partial correlations), when whole brain, hippocampal regions of interest, and posterior:anterior hippocampal ratios were examined, and across different participant sub-groups (divided by gender and task performance). Variations in hippocampal grey matter myelin and iron levels may not, therefore, help to explain individual differences in performance on hippocampal-dependent tasks, at least in young, healthy individuals.

Download Full-text

Preclinical Evaluation of [18F]FACH in Healthy Mice and Piglets: An 18F-Labeled Ligand for Imaging of Monocarboxylate Transporters with PET

International Journal of Molecular Sciences ◽

10.3390/ijms22041645 ◽

2021 ◽

Vol 22 (4) ◽

pp. 1645

Author(s):

Daniel Gündel ◽

Masoud Sadeghzadeh ◽

Winnie Deuther-Conrad ◽

Barbara Wenzel ◽

Paul Cumming ◽

...

Keyword(s):

Molecular Imaging ◽

Ex Vivo ◽

Specific Binding ◽

Monocarboxylate Transporters ◽

Binding Potential ◽

Kidney Cortex ◽

Binding Studies ◽

Imaging Tool ◽

Pre Treatment

The expression of monocarboxylate transporters (MCTs) is linked to pathophysiological changes in diseases, including cancer, such that MCTs could potentially serve as diagnostic markers or therapeutic targets. We recently developed [18F]FACH as a radiotracer for non-invasive molecular imaging of MCTs by positron emission tomography (PET). The aim of this study was to evaluate further the specificity, metabolic stability, and pharmacokinetics of [18F]FACH in healthy mice and piglets. We measured the [18F]FACH plasma protein binding fractions in mice and piglets and the specific binding in cryosections of murine kidney and lung. The biodistribution of [18F]FACH was evaluated by tissue sampling ex vivo and by dynamic PET/MRI in vivo, with and without pre-treatment by the MCT inhibitor α-CCA-Na or the reference compound, FACH-Na. Additionally, we performed compartmental modelling of the PET signal in kidney cortex and liver. Saturation binding studies in kidney cortex cryosections indicated a KD of 118 ± 12 nM and Bmax of 6.0 pmol/mg wet weight. The specificity of [18F]FACH uptake in the kidney cortex was confirmed in vivo by reductions in AUC0–60min after pre-treatment with α-CCA-Na in mice (−47%) and in piglets (−66%). [18F]FACH was metabolically stable in mouse, but polar radio-metabolites were present in plasma and tissues of piglets. The [18F]FACH binding potential (BPND) in the kidney cortex was approximately 1.3 in mice. The MCT1 specificity of [18F]FACH uptake was confirmed by displacement studies in 4T1 cells. [18F]FACH has suitable properties for the detection of the MCTs in kidney, and thus has potential as a molecular imaging tool for MCT-related pathologies, which should next be assessed in relevant disease models.

Download Full-text

Harnessing PET to track micro- and nanoplastics in vivo

Scientific Reports ◽

10.1038/s41598-021-90929-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Outi Keinänen ◽

Eric J. Dayts ◽

Cindy Rodriguez ◽

Samantha M. Sarrett ◽

James M. Brennan ◽

...

Keyword(s):

Sea Water ◽

Accurate Determination ◽

Nuclear Imaging ◽

Imaging Data ◽

Biodistribution Studies ◽

Positron Emission ◽

20 Nm ◽

Pharmacokinetic Behavior

AbstractThe proliferation of plastics in the environment continues at an alarming rate. Plastic particles have been found to be persistent and ubiquitous pollutants in a variety of environments, including sea water, fresh water, soil, and air. In light of this phenomenon, the scientific and medical communities have become increasingly wary of the dangers posed to human health by chronic exposure to microplastics (< 5 mm diameter) and nanoplastics (< 100 nm diameter). A critical component of the study of the health effects of these pollutants is the accurate determination of their pharmacokinetic behavior in vivo. Herein, we report the first use of molecular imaging to track polystyrene (PS) micro- and nanoplastic particles in mammals. To this end, we have modified PS particles of several sizes—diameters of 20 nm, 220 nm, 1 µm, and 6 µm—with the chelator desferrioxamine (DFO) and radiolabeled these DFO-bearing particles with the positron-emitting radiometal zirconium-89 (89Zr; t1/2 ~ 3.3 d). Subsequently, positron emission tomography (PET) was used to visualize the biodistribution of these radioplastics in C57BL/6J mice at 6, 12, 24, and 48 h after ingestion. The imaging data reveal that the majority of the radioplastics remain in the gastrointestinal tract and are eliminated through the feces by 48 h post-ingestion, a result reinforced by acute biodistribution studies. Ultimately, this work suggests that nuclear imaging—and PET in particular—can be a sensitive and effective tool in the urgent and rapidly growing effort to study the in vivo behavior and potential toxicity of micro- and nanoplastics.

Download Full-text

Recovery of photoacoustic images based on accurate ultrasound positioning

Visual Computing for Industry Biomedicine and Art ◽

10.1186/s42492-021-00072-2 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Yinhao Pan ◽

Ningbo Chen ◽

Liangjian Liu ◽

Chengbo Liu ◽

Zhiqiang Xu ◽

...

Keyword(s):

Biological Tissue ◽

Large Field ◽

Photoacoustic Microscopy ◽

Label Free ◽

Imaging Data ◽

Motor Speed ◽

Image Correction ◽

Microscopy Imaging ◽

Scanning Method

AbstractPhotoacoustic microscopy is an in vivo imaging technology based on the photoacoustic effect. It is widely used in various biomedical studies because it can provide high-resolution images while being label-free, safe, and harmless to biological tissue. Polygon-scanning is an effective scanning method in photoacoustic microscopy that can realize fast imaging of biological tissue with a large field of view. However, in polygon-scanning, fluctuations of the rotating motor speed and the geometric error of the rotating mirror cause image distortions, which seriously affect the photoacoustic-microscopy imaging quality. To improve the image quality of photoacoustic microscopy using polygon-scanning, an image correction method is proposed based on accurate ultrasound positioning. In this method, the photoacoustic and ultrasound imaging data of the sample are simultaneously obtained, and the angle information of each mirror used in the polygon-scanning is extracted from the ultrasonic data to correct the photoacoustic images. Experimental results show that the proposed method can significantly reduce image distortions in photoacoustic microscopy, with the image dislocation offset decreasing from 24.774 to 10.365 μm.

Download Full-text