Editorial

4 pages, 188 KiB

Open AccessEditorial

Molecular Imaging of Immunity and Inflammation and Its Impact on Precision Medicine

by Moritz Wildgruber and Michel Eisenblätter

Biomedicines 2021, 9(1), 62; https://doi.org/10.3390/biomedicines9010062 - 11 Jan 2021

Viewed by 1611

Biomedical research has, over the past decades, found components of the immune system at the functional center of almost every pathophysiological condition and disease [...] Full article

(This article belongs to the Special Issue Advanced Research in Molecular Imaging of Immunity and Inflammation)

Research

Jump to: Editorial, Review

14 pages, 2253 KiB

Open AccessArticle

Combined HP ¹³C Pyruvate and ¹³C-Glucose Fluxomic as a Potential Marker of Response to Targeted Therapies in YUMM1.7 Melanoma Xenografts

by Chantale Farah, Marie-Aline Neveu, Caner Yelek, Caroline Bouzin, Bernard Gallez, Jean-François Baurain, Lionel Mignion and Bénédicte F. Jordan

Biomedicines 2022, 10(3), 717; https://doi.org/10.3390/biomedicines10030717 - 19 Mar 2022

Cited by 4 | Viewed by 2450

Abstract

A vast majority of BRAF V600E mutated melanoma patients will develop resistance to combined BRAF/MEK inhibition after initial clinical response. Resistance to targeted therapy is described to be accompanied by specific metabolic changes in melanoma. The aim of this work was to evaluate [...] Read more.

A vast majority of BRAF V600E mutated melanoma patients will develop resistance to combined BRAF/MEK inhibition after initial clinical response. Resistance to targeted therapy is described to be accompanied by specific metabolic changes in melanoma. The aim of this work was to evaluate metabolic imaging using ¹³C-MRS (Magnetic Resonance Spectroscopy) as a marker of response to BRAF/MEK inhibition in a syngeneic melanoma model. Tumor growth was significantly delayed in mice bearing YUMM1.7 melanoma xenografts treated with the BRAF inhibitor vemurafenib, and/or with the MEK inhibitor trametinib, in comparison with the control group. ¹³C-MRS was performed in vivo after injection of hyperpolarized (HP) ¹³C-pyruvate, at baseline and 24 h after treatment, to evaluate dynamic changes in pyruvate-lactate exchange. Furthermore, ex vivo ¹³C-MRS steady state metabolic tracing experiments were performed after U-¹³C-glucose or 5-¹³C-glutamine injection, 24 h after treatment. The HP ¹³C-lactate-to-pyruvate ratio was not modified in response to BRAF/MEK inhibition, whereas the production of ¹³C-lactate from ¹³C-glucose was significantly reduced 24 h after treatment with vemurafenib, trametinib, or with the combined inhibitors. Conversely, ¹³C-glutamine metabolism was not modified in response to BRAF/MEK inhibition. In conclusion, we identified ¹³C-glucose fluxomic as a potential marker of response to BRAF/MEK inhibition in YUMM1.7 melanoma xenografts. Full article

(This article belongs to the Special Issue Advanced Research in Molecular Imaging of Immunity and Inflammation)

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14 pages, 5625 KiB

Open AccessArticle

Diffusion Weighted Imaging and T2 Mapping Detect Inflammatory Response in the Renal Tissue during Ischemia Induced Acute Kidney Injury in Different Mouse Strains and Predict Renal Outcome

by Robert Greite, Katja Derlin, Dagmar Hartung, Rongjun Chen, Martin Meier, Marcel Gutberlet, Bennet Hensen, Frank Wacker, Faikah Gueler and Susanne Hellms

Biomedicines 2021, 9(8), 1071; https://doi.org/10.3390/biomedicines9081071 - 23 Aug 2021

Cited by 5 | Viewed by 2255

Abstract

To characterize ischemia reperfusion injury (IRI)-induced acute kidney injury (AKI) in C57BL/6 (B6) and CD1-mice by longitudinal functional MRI-measurement of edema formation (T2-mapping) and inflammation (diffusion weighted imaging (DWI)). IRI was induced with unilateral right renal pedicle clamping for 35min. 7T-MRI was performed [...] Read more.

To characterize ischemia reperfusion injury (IRI)-induced acute kidney injury (AKI) in C57BL/6 (B6) and CD1-mice by longitudinal functional MRI-measurement of edema formation (T2-mapping) and inflammation (diffusion weighted imaging (DWI)). IRI was induced with unilateral right renal pedicle clamping for 35min. 7T-MRI was performed 1 and 14 days after surgery. DWI (7 b-values) and multiecho TSE sequences (7 TE) were acquired. Parameters were quantified in relation to the contralateral kidney on day 1 (d1). Renal MCP-1 and IL-6-levels were measured by qPCR and serum-CXCL13 by ELISA. Immunohistochemistry for fibronectin and collagen-4 was performed. T2-increase on d1 was higher in the renal cortex (127 ± 5% vs. 94 ± 6%, p < 0.01) and the outer stripe of the outer medulla (141 ± 9% vs. 111 ± 9%, p < 0.05) in CD1, indicating tissue edema. Medullary diffusivity was more restricted in CD1 than B6 (d1: 73 ± 3% vs. 90 ± 2%, p < 0.01 and d14: 77 ± 5% vs. 98 ± 3%, p < 0.01). Renal MCP-1 and IL-6-expression as well as systemic CXCL13-release were pronounced in CD1 on d1 after IRI. Renal fibrosis was detected in CD1 on d14. T2-increase and ADC-reduction on d1 correlated with kidney volume loss on d14 (r = 0.7, p < 0.05; r = 0.6, p < 0.05) and could serve as predictive markers. T2-mapping and DWI evidenced higher susceptibility to ischemic AKI in CD1 compared to B6. Full article

(This article belongs to the Special Issue Advanced Research in Molecular Imaging of Immunity and Inflammation)

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14 pages, 2353 KiB

Open AccessArticle

Effective Detection and Monitoring of Glioma Using [¹⁸F]FPIA PET Imaging

by Vessela Vassileva, Marta Braga, Chris Barnes, Justyna Przystal, Ali Ashek, Louis Allott, Diana Brickute, Joel Abrahams, Keittisak Suwan, Angel M. Carcaboso, Amin Hajitou and Eric O. Aboagye

Biomedicines 2021, 9(7), 811; https://doi.org/10.3390/biomedicines9070811 - 13 Jul 2021

Cited by 6 | Viewed by 4579

Abstract

Background: Reprogrammed cellular metabolism is a cancer hallmark. In addition to increased glycolysis, the oxidation of acetate in the citric acid cycle is another common metabolic phenotype. We have recently developed a novel fluorine-18-labelled trimethylacetate-based radiotracer, [¹⁸F]fluoro-pivalic acid ([¹⁸F]FPIA), [...] Read more.

Background: Reprogrammed cellular metabolism is a cancer hallmark. In addition to increased glycolysis, the oxidation of acetate in the citric acid cycle is another common metabolic phenotype. We have recently developed a novel fluorine-18-labelled trimethylacetate-based radiotracer, [¹⁸F]fluoro-pivalic acid ([¹⁸F]FPIA), for imaging the transcellular flux of short-chain fatty acids, and investigated whether this radiotracer can be used for the detection of glioma growth. Methods: We evaluated the potential of [¹⁸F]FPIA PET to monitor tumor growth in orthotopic patient-derived (HSJD-GBM-001) and cell line-derived (U87, LN229) glioma xenografts, and also included [¹⁸F]FDG PET for comparison. We assessed proliferation (Ki-67) and the expression of lipid metabolism and transport proteins (CPT1, SLC22A2, SLC22A5, SLC25A20) by immunohistochemistry, along with etomoxir treatment to provide insights into [¹⁸F]FPIA uptake. Results: Longitudinal PET imaging showed gradual increase in [¹⁸F]FPIA uptake in orthotopic glioma models with disease progression (p < 0.0001), and high tumor-to-brain contrast compared to [¹⁸F]FDG (p < 0.0001). [¹⁸F]FPIA uptake correlated positively with Ki-67 (p < 0.01), SLC22A5 (p < 0.001) and SLC25A20 (p = 0.001), and negatively with CPT1 (p < 0.01) and SLC22A2 (p < 0.01). Etomoxir reduced [¹⁸F]FPIA uptake, which correlated with decreased Ki-67 (p < 0.05). Conclusions: Our findings support the use of [¹⁸F]FPIA PET for the detection and longitudinal monitoring of glioma, showing a positive correlation with tumor proliferation, and suggest transcellular flux-mediated radiotracer uptake. Full article

(This article belongs to the Special Issue Advanced Research in Molecular Imaging of Immunity and Inflammation)

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27 pages, 7565 KiB

Open AccessArticle

Imaging of Inflammation in Spinal Cord Injury: Novel Insights on the Usage of PFC-Based Contrast Agents

by Francesca Garello, Marina Boido, Martina Miglietti, Valeria Bitonto, Marco Zenzola, Miriam Filippi, Francesca Arena, Lorena Consolino, Matilde Ghibaudi and Enzo Terreno

Biomedicines 2021, 9(4), 379; https://doi.org/10.3390/biomedicines9040379 - 03 Apr 2021

Cited by 7 | Viewed by 2725

Abstract

Labeling of macrophages with perfluorocarbon (PFC)-based compounds allows the visualization of inflammatory processes by ¹⁹F-magnetic resonance imaging (¹⁹F-MRI), due to the absence of endogenous background. Even if PFC-labeling of monocytes/macrophages has been largely investigated and used, information is lacking about [...] Read more.

Labeling of macrophages with perfluorocarbon (PFC)-based compounds allows the visualization of inflammatory processes by ¹⁹F-magnetic resonance imaging (¹⁹F-MRI), due to the absence of endogenous background. Even if PFC-labeling of monocytes/macrophages has been largely investigated and used, information is lacking about the impact of these agents over the polarization towards one of their cell subsets and on the best way to image them. In the present work, a PFC-based nanoemulsion was developed to monitor the course of inflammation in a model of spinal cord injury (SCI), a pathology in which the understanding of immunological events is of utmost importance to select the optimal therapeutic strategies. The effects of PFC over macrophage polarization were studied in vitro, on cultured macrophages, and in vivo, in a mouse SCI model, by testing and comparing various cell tracking protocols, including single and multiple administrations, the use of MRI or Point Resolved Spectroscopy (PRESS), and application of pre-saturation of Kupffer cells. The blood half-life of nanoemulsion was also investigated by ¹⁹F Magnetic Resonance Spectroscopy (MRS). In vitro and in vivo results indicate the occurrence of a switch towards the M2 (anti-inflammatory) phenotype, suggesting a possible theranostic function of these nanoparticles. The comparative work presented here allows the reader to select the most appropriate protocol according to the research objectives (quantitative data acquisition, visual monitoring of macrophage recruitment, theranostic purpose, rapid MRI acquisition, etc.). Finally, the method developed here to determine the blood half-life of the PFC nanoemulsion can be extended to other fluorinated compounds. Full article

(This article belongs to the Special Issue Advanced Research in Molecular Imaging of Immunity and Inflammation)

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13 pages, 1311 KiB

Open AccessArticle

Hyperpolarized ¹³C Spectroscopy with Simple Slice-and-Frequency-Selective Excitation

by Geoffrey J. Topping, Irina Heid, Marija Trajkovic-Arsic, Lukas Kritzner, Martin Grashei, Christian Hundshammer, Maximilian Aigner, Jason G. Skinner, Rickmer Braren and Franz Schilling

Biomedicines 2021, 9(2), 121; https://doi.org/10.3390/biomedicines9020121 - 27 Jan 2021

Cited by 6 | Viewed by 2028

Abstract

Hyperpolarized ¹³C nuclear magnetic resonance spectroscopy can characterize in vivo tissue metabolism, including preclinical models of cancer and inflammatory disease. Broad bandwidth radiofrequency excitation is often paired with free induction decay readout for spectral separation, but quantification of low-signal downstream metabolites using [...] Read more.

Hyperpolarized ¹³C nuclear magnetic resonance spectroscopy can characterize in vivo tissue metabolism, including preclinical models of cancer and inflammatory disease. Broad bandwidth radiofrequency excitation is often paired with free induction decay readout for spectral separation, but quantification of low-signal downstream metabolites using this method can be impeded by spectral peak overlap or when frequency separation of the detected peaks exceeds the excitation bandwidth. In this work, alternating frequency narrow bandwidth (250 Hz) slice-selective excitation was used for ¹³C spectroscopy at 7 T in a subcutaneous xenograft rat model of human pancreatic cancer (PSN1) to improve quantification while measuring the dynamics of injected hyperpolarized [1-¹³C]lactate and its metabolite [1-¹³C]pyruvate. This method does not require sophisticated pulse sequences or specialized radiofrequency and gradient pulses, but rather uses nominally spatially offset slices to produce alternating frequency excitation with simpler slice-selective radiofrequency pulses. Additionally, point-resolved spectroscopy was used to calibrate the ¹³C frequency from the thermal proton signal in the target region. This excitation scheme isolates the small [1-¹³C]pyruvate peak from the similar-magnitude tail of the much larger injected [1-¹³C]lactate peak, facilitates quantification of the [1-¹³C]pyruvate signal, simplifies data processing, and could be employed for other substrates and preclinical models. Full article

(This article belongs to the Special Issue Advanced Research in Molecular Imaging of Immunity and Inflammation)

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11 pages, 1663 KiB

Open AccessArticle

S100A9-Imaging Enables Estimation of Early Therapy-Mediated Changes in the Inflammatory Tumor Microenvironment

by Anne Helfen, Annika Schnepel, Jan Rieß, Miriam Stölting, Mirjam Gerwing, Max Masthoff, Thomas Vogl, Johannes Roth, Carsten Höltke, Moritz Wildgruber and Michel Eisenblätter

Biomedicines 2021, 9(1), 29; https://doi.org/10.3390/biomedicines9010029 - 03 Jan 2021

Cited by 2 | Viewed by 2394

Abstract

(1) Background: The prognosis of cancer is dependent on immune cells in the tumor microenvironment (TME). The protein S100A9 is an essential regulator of the TME, associated with poor prognosis. In this study, we evaluated early therapy effects on the TME in syngeneic [...] Read more.

(1) Background: The prognosis of cancer is dependent on immune cells in the tumor microenvironment (TME). The protein S100A9 is an essential regulator of the TME, associated with poor prognosis. In this study, we evaluated early therapy effects on the TME in syngeneic murine breast cancer via S100A9-specific in vivo imaging. (2) Methods: Murine 4T1 cells were implanted orthotopically in female BALB/c mice (n = 59). Tumor size-adapted fluorescence imaging was performed before and 5 days after chemo- (Doxorubicin, n = 20), anti-angiogenic therapy (Bevacizumab, n = 20), or placebo (NaCl, n = 19). Imaging results were validated ex vivo (immunohistochemistry, flow cytometry). (3) Results: While tumor growth revealed no differences (p = 0.48), fluorescence intensities (FI) for S100A9 in Bevacizumab-treated tumors were significantly lower as compared to Doxorubicin (2.60 vs. 15.65 AU, p < 0.0001). FI for Doxorubicin were significantly higher compared to placebo (8.95 AU, p = 0.01). Flow cytometry revealed shifts in monocytic and T-cell cell infiltrates under therapy, correlating with imaging. (4) Conclusions: S100A9-specific imaging enables early detection of therapy effects visualizing immune cell activity in the TME, even before clinically detectable changes in tumor size. Therefore, it may serve as a non-invasive imaging biomarker for early therapy effects. Full article

(This article belongs to the Special Issue Advanced Research in Molecular Imaging of Immunity and Inflammation)

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15 pages, 1685 KiB

Open AccessArticle

Monitoring Endothelin-A Receptor Expression during the Progression of Atherosclerosis

by Miriam Stölting, Christiane Geyer, Anne Helfen, Anke Hahnenkamp, Marco V. Usai, Eva Wardelmann, Michael T. Kuhlmann, Moritz Wildgruber and Carsten Höltke

Biomedicines 2020, 8(12), 538; https://doi.org/10.3390/biomedicines8120538 - 26 Nov 2020

Cited by 2 | Viewed by 1874

Abstract

Cardiovascular disease remains the most frequent cause of death worldwide. Atherosclerosis, an underlying cause of cardiovascular disease, is an inflammatory disorder associated with endothelial dysfunction. The endothelin system plays a crucial role in the pathogenesis of endothelial dysfunction and is involved in the [...] Read more.

Cardiovascular disease remains the most frequent cause of death worldwide. Atherosclerosis, an underlying cause of cardiovascular disease, is an inflammatory disorder associated with endothelial dysfunction. The endothelin system plays a crucial role in the pathogenesis of endothelial dysfunction and is involved in the development of atherosclerosis. We aimed to reveal the expression levels of the endothelin-A receptor (ET_AR) in the course of atherogenesis to reveal possible time frames for targeted imaging and interventions. We used the ApoE^−/− mice model and human specimens and evaluated ET_AR expression by quantitative rtPCR (qPCR), histology and fluorescence molecular imaging. We found a significant upregulation of ET_AR after 22 weeks of high-fat diet in the aortae of ApoE^−/− mice. With regard to translation to human disease, we applied the fluorescent probe to fresh explants of human carotid and femoral artery specimens. The findings were correlated with qPCR and histology. While ET_AR is upregulated during the progression of early atherosclerosis in the ApoE^−/− mouse model, we found that ET_AR expression is substantially reduced in advanced human atherosclerotic plaques. Moreover, those expression changes were clearly depicted by fluorescence imaging using our in-house designed ET_AR-Cy 5.5 probe confirming its specificity and potential use in future studies. Full article

(This article belongs to the Special Issue Advanced Research in Molecular Imaging of Immunity and Inflammation)

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11 pages, 2947 KiB

Open AccessArticle

Native T1 Mapping Magnetic Resonance Imaging as a Quantitative Biomarker for Characterization of the Extracellular Matrix in a Rabbit Hepatic Cancer Model

by Sarah Keller, Tabea Borde, Julia Brangsch, Lisa C. Adams, Avan Kader, Carolin Reimann, Pimrapat Gebert, Bernd Hamm and Marcus Makowski

Biomedicines 2020, 8(10), 412; https://doi.org/10.3390/biomedicines8100412 - 13 Oct 2020

Cited by 7 | Viewed by 2285

Abstract

To characterize the tumor extracellular matrix (ECM) using native T1 mapping magnetic resonance imaging (MRI) in an experimental hepatic cancer model, a total of 27 female New Zealand white rabbits with hepatic VX2 tumors were examined by MRI at different time points following [...] Read more.

To characterize the tumor extracellular matrix (ECM) using native T1 mapping magnetic resonance imaging (MRI) in an experimental hepatic cancer model, a total of 27 female New Zealand white rabbits with hepatic VX2 tumors were examined by MRI at different time points following tumor implantation (day 14, 21, 28). A steady-state precession readout single-shot MOLLI sequence was acquired in a 3 T MRI scanner in prone position using a head-neck coil. The tumors were segmented into a central, marginal, and peritumoral region in anatomical images and color-coded T1 maps. In histopathological sections, stained with H&E and Picrosirius red, the regions corresponded to central tumor necrosis and accumulation of viable cells with fibrosis in the tumor periphery. Another region of interest (ROI) was placed in healthy liver tissue. T1 times were correlated with quantitative data of collagen area staining. A two-way repeated-measures ANOVA was used to compare cohorts and tumor regions. Hepatic tumors were successfully induced in all rabbits. T1 mapping demonstrated significant differences between the different tumor regions (F(1.43,34.26) = 106.93, p < 0.001) without interaction effects between time points and regions (F(2.86,34.26) = 0.74, p = 0.53). In vivo T1 times significantly correlated with ex vivo collagen stains (area %), (center: r = 0.78, p < 0.001; margin: r = 0.84, p < 0.001; peritumoral: r = 0.73, p < 0.001). Post hoc tests using Sidak’s correction revealed significant differences in T1 times between all three regions (p < 0.001). Native T1 mapping is feasible and allows the differentiation of tumor regions based on ECM composition in a longitudinal tumor study in an experimental small animal model, making it a potential quantitative biomarker of ECM remodeling and a promising technique for future treatment studies. Full article

(This article belongs to the Special Issue Advanced Research in Molecular Imaging of Immunity and Inflammation)

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Review

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26 pages, 3268 KiB

Open AccessReview

The Development of Nanoparticles for the Detection and Imaging of Ovarian Cancers

by Edward Henderson, Gabriel Huynh, Kirsty Wilson, Magdalena Plebanski and Simon Corrie

Biomedicines 2021, 9(11), 1554; https://doi.org/10.3390/biomedicines9111554 - 28 Oct 2021

Cited by 2 | Viewed by 2875

Abstract

Ovarian cancer remains as one of the most lethal gynecological cancers to date, with major challenges associated with screening, diagnosis and treatment of the disease and an urgent need for new technologies that can meet these challenges. Nanomaterials provide new opportunities in diagnosis [...] Read more.

Ovarian cancer remains as one of the most lethal gynecological cancers to date, with major challenges associated with screening, diagnosis and treatment of the disease and an urgent need for new technologies that can meet these challenges. Nanomaterials provide new opportunities in diagnosis and therapeutic management of many different types of cancers. In this review, we highlight recent promising developments of nanoparticles designed specifically for the detection or imaging of ovarian cancer that have reached the preclinical stage of development. This includes contrast agents, molecular imaging agents and intraoperative aids that have been designed for integration into standard imaging procedures. While numerous nanoparticle systems have been developed for ovarian cancer detection and imaging, specific design criteria governing nanomaterial targeting, biodistribution and clearance from the peritoneal cavity remain key challenges that need to be overcome before these promising tools can accomplish significant breakthroughs into the clinical setting. Full article

(This article belongs to the Special Issue Advanced Research in Molecular Imaging of Immunity and Inflammation)

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18 pages, 3938 KiB

Open AccessReview

Optoacoustic Imaging in Inflammation

by Adrian P. Regensburger, Emma Brown, Gerhard Krönke, Maximilian J. Waldner and Ferdinand Knieling

Biomedicines 2021, 9(5), 483; https://doi.org/10.3390/biomedicines9050483 - 28 Apr 2021

Cited by 22 | Viewed by 4166

Abstract

Optoacoustic or photoacoustic imaging (OAI/PAI) is a technology which enables non-invasive visualization of laser-illuminated tissue by the detection of acoustic signals. The combination of “light in” and “sound out” offers unprecedented scalability with a high penetration depth and resolution. The wide range of [...] Read more.

Optoacoustic or photoacoustic imaging (OAI/PAI) is a technology which enables non-invasive visualization of laser-illuminated tissue by the detection of acoustic signals. The combination of “light in” and “sound out” offers unprecedented scalability with a high penetration depth and resolution. The wide range of biomedical applications makes this technology a versatile tool for preclinical and clinical research. Particularly when imaging inflammation, the technology offers advantages over current clinical methods to diagnose, stage, and monitor physiological and pathophysiological processes. This review discusses the clinical perspective of using OAI in the context of imaging inflammation as well as in current and emerging translational applications. Full article

(This article belongs to the Special Issue Advanced Research in Molecular Imaging of Immunity and Inflammation)

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20 pages, 4850 KiB

Open AccessReview

Tumor-Associated Macrophages—Implications for Molecular Oncology and Imaging

by Melanie A. Kimm, Christopher Klenk, Marianna Alunni-Fabbroni, Sophia Kästle, Matthias Stechele, Jens Ricke, Michel Eisenblätter and Moritz Wildgruber

Biomedicines 2021, 9(4), 374; https://doi.org/10.3390/biomedicines9040374 - 02 Apr 2021

Cited by 10 | Viewed by 2879

Abstract

Tumor-associated macrophages (TAMs) represent the largest group of leukocytes within the tumor microenvironment (TME) of solid tumors and orchestrate the composition of anti- as well as pro-tumorigenic factors. This makes TAMs an excellent target for novel cancer therapies. The plasticity of TAMs resulting [...] Read more.

Tumor-associated macrophages (TAMs) represent the largest group of leukocytes within the tumor microenvironment (TME) of solid tumors and orchestrate the composition of anti- as well as pro-tumorigenic factors. This makes TAMs an excellent target for novel cancer therapies. The plasticity of TAMs resulting in varying membrane receptors and expression of intracellular proteins allow the specific characterization of different subsets of TAMs. Those markers similarly allow tracking of TAMs by different means of molecular imaging. This review aims to provides an overview of the origin of tumor-associated macrophages, their polarization in different subtypes, and how characteristic markers of the subtypes can be used as targets for molecular imaging and theranostic approaches. Full article

(This article belongs to the Special Issue Advanced Research in Molecular Imaging of Immunity and Inflammation)

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24 pages, 2225 KiB

Open AccessReview

Imaging Inflammation with Positron Emission Tomography

by Janette Iking, Magdalena Staniszewska, Lukas Kessler, Jasmin M. Klose, Katharina Lückerath, Wolfgang P. Fendler, Ken Herrmann and Christoph Rischpler

Biomedicines 2021, 9(2), 212; https://doi.org/10.3390/biomedicines9020212 - 19 Feb 2021

Cited by 30 | Viewed by 4833

Abstract

The impact of inflammation on the outcome of many medical conditions such as cardiovascular diseases, neurological disorders, infections, cancer, and autoimmune diseases has been widely acknowledged. However, in contrast to neurological, oncologic, and cardiovascular disorders, imaging plays a minor role in research and [...] Read more.

The impact of inflammation on the outcome of many medical conditions such as cardiovascular diseases, neurological disorders, infections, cancer, and autoimmune diseases has been widely acknowledged. However, in contrast to neurological, oncologic, and cardiovascular disorders, imaging plays a minor role in research and management of inflammation. Imaging can provide insights into individual and temporospatial biology and grade of inflammation which can be of diagnostic, therapeutic, and prognostic value. There is therefore an urgent need to evaluate and understand current approaches and potential applications for imaging of inflammation. This review discusses radiotracers for positron emission tomography (PET) that have been used to image inflammation in cardiovascular diseases and other inflammatory conditions with a special emphasis on radiotracers that have already been successfully applied in clinical settings. Full article

(This article belongs to the Special Issue Advanced Research in Molecular Imaging of Immunity and Inflammation)

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26 pages, 1725 KiB

Open AccessReview

Evaluation of Plaque Characteristics and Inflammation Using Magnetic Resonance Imaging

by Kristina Andelovic, Patrick Winter, Peter Michael Jakob, Wolfgang Rudolf Bauer, Volker Herold and Alma Zernecke

Biomedicines 2021, 9(2), 185; https://doi.org/10.3390/biomedicines9020185 - 12 Feb 2021

Cited by 10 | Viewed by 3106

Abstract

Atherosclerosis is an inflammatory disease of large and medium-sized arteries, characterized by the growth of atherosclerotic lesions (plaques). These plaques often develop at inner curvatures of arteries, branchpoints, and bifurcations, where the endothelial wall shear stress is low and oscillatory. In conjunction with [...] Read more.

Atherosclerosis is an inflammatory disease of large and medium-sized arteries, characterized by the growth of atherosclerotic lesions (plaques). These plaques often develop at inner curvatures of arteries, branchpoints, and bifurcations, where the endothelial wall shear stress is low and oscillatory. In conjunction with other processes such as lipid deposition, biomechanical factors lead to local vascular inflammation and plaque growth. There is also evidence that low and oscillatory shear stress contribute to arterial remodeling, entailing a loss in arterial elasticity and, therefore, an increased pulse-wave velocity. Although altered shear stress profiles, elasticity and inflammation are closely intertwined and critical for plaque growth, preclinical and clinical investigations for atherosclerosis mostly focus on the investigation of one of these parameters only due to the experimental limitations. However, cardiovascular magnetic resonance imaging (MRI) has been demonstrated to be a potent tool which can be used to provide insights into a large range of biological parameters in one experimental session. It enables the evaluation of the dynamic process of atherosclerotic lesion formation without the need for harmful radiation. Flow-sensitive MRI provides the assessment of hemodynamic parameters such as wall shear stress and pulse wave velocity which may replace invasive and radiation-based techniques for imaging of the vascular function and the characterization of early plaque development. In combination with inflammation imaging, the analyses and correlations of these parameters could not only significantly advance basic preclinical investigations of atherosclerotic lesion formation and progression, but also the diagnostic clinical evaluation for early identification of high-risk plaques, which are prone to rupture. In this review, we summarize the key applications of magnetic resonance imaging for the evaluation of plaque characteristics through flow sensitive and morphological measurements. The simultaneous measurements of functional and structural parameters will further preclinical research on atherosclerosis and has the potential to fundamentally improve the detection of inflammation and vulnerable plaques in patients. Full article

(This article belongs to the Special Issue Advanced Research in Molecular Imaging of Immunity and Inflammation)

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23 pages, 5548 KiB

Open AccessReview

Molecular Imaging of Inflammatory Disease

by Meredith A. Jones, William M. MacCuaig, Alex N. Frickenstein, Seda Camalan, Metin N. Gurcan, Jennifer Holter-Chakrabarty, Katherine T. Morris, Molly W. McNally, Kristina K. Booth, Steven Carter, William E. Grizzle and Lacey R. McNally

Biomedicines 2021, 9(2), 152; https://doi.org/10.3390/biomedicines9020152 - 04 Feb 2021

Cited by 8 | Viewed by 3633

Abstract

Inflammatory diseases include a wide variety of highly prevalent conditions with high mortality rates in severe cases ranging from cardiovascular disease, to rheumatoid arthritis, to chronic obstructive pulmonary disease, to graft vs. host disease, to a number of gastrointestinal disorders. Many diseases that [...] Read more.

Inflammatory diseases include a wide variety of highly prevalent conditions with high mortality rates in severe cases ranging from cardiovascular disease, to rheumatoid arthritis, to chronic obstructive pulmonary disease, to graft vs. host disease, to a number of gastrointestinal disorders. Many diseases that are not considered inflammatory per se are associated with varying levels of inflammation. Imaging of the immune system and inflammatory response is of interest as it can give insight into disease progression and severity. Clinical imaging technologies such as computed tomography (CT) and magnetic resonance imaging (MRI) are traditionally limited to the visualization of anatomical information; then, the presence or absence of an inflammatory state must be inferred from the structural abnormalities. Improvement in available contrast agents has made it possible to obtain functional information as well as anatomical. In vivo imaging of inflammation ultimately facilitates an improved accuracy of diagnostics and monitoring of patients to allow for better patient care. Highly specific molecular imaging of inflammatory biomarkers allows for earlier diagnosis to prevent irreversible damage. Advancements in imaging instruments, targeted tracers, and contrast agents represent a rapidly growing area of preclinical research with the hopes of quick translation to the clinic. Full article

(This article belongs to the Special Issue Advanced Research in Molecular Imaging of Immunity and Inflammation)

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17 pages, 2874 KiB

Open AccessReview

Molecular MR Imaging of Prostate Cancer

by Avan Kader, Julia Brangsch, Jan O. Kaufmann, Jing Zhao, Dilyana B. Mangarova, Jana Moeckel, Lisa C. Adams, Ingolf Sack, Matthias Taupitz, Bernd Hamm and Marcus R. Makowski

Biomedicines 2021, 9(1), 1; https://doi.org/10.3390/biomedicines9010001 - 22 Dec 2020

Cited by 4 | Viewed by 3059

Abstract

This review summarizes recent developments regarding molecular imaging markers for magnetic resonance imaging (MRI) of prostate cancer (PCa). Currently, the clinical standard includes MR imaging using unspecific gadolinium-based contrast agents. Specific molecular probes for the diagnosis of PCa could improve the molecular characterization [...] Read more.

This review summarizes recent developments regarding molecular imaging markers for magnetic resonance imaging (MRI) of prostate cancer (PCa). Currently, the clinical standard includes MR imaging using unspecific gadolinium-based contrast agents. Specific molecular probes for the diagnosis of PCa could improve the molecular characterization of the tumor in a non-invasive examination. Furthermore, molecular probes could enable targeted therapies to suppress tumor growth or reduce the tumor size. Full article

(This article belongs to the Special Issue Advanced Research in Molecular Imaging of Immunity and Inflammation)

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