Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2020-09-16)
    Abstract: Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease with an up to 80% mortality in case of rupture. Current biomarkers fail to account for size-independent risk of rupture. By combining the information of different molecular probes, multi-target molecular MRI holds the potential to enable individual characterization of AAA. In this experimental study, we aimed to examine the feasibility of simultaneous imaging of extracellular collagen and inflammation for size-independent prediction of risk of rupture in murine AAA. The study design consisted of: (1) A outcome-based longitudinal study with imaging performed once after one week with follow-up and death as the end-point for assessment of rupture risk. (2) A week-by-week study for the characterization of AAA development with imaging after 1, 2, 3 and 4 weeks. For both studies, the animals were administered a type 1 collagen-targeted gadolinium-based probe (surrogate marker for extracellular matrix (ECM) remodeling) and an iron oxide-based probe (surrogate marker for inflammatory activity), in one imaging session. In vivo measurements of collagen and iron oxide probes showed a significant correlation with ex vivo histology (p  〈  0.001) and also corresponded well to inductively-coupled plasma-mass spectrometry and laser-ablation inductively-coupled plasma mass spectrometry. Combined evaluation of collagen-related ECM remodeling and inflammatory activity was the most accurate predictor for AAA rupture (sensitivity 80%, specificity 100%, area under the curve 0.85), being superior to information from the individual probes alone. Our study supports the feasibility of a simultaneous assessment of collagen-related extracellular matrix remodeling and inflammatory activity in a murine model of AAA.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2615211-3
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 1 ( 2022-12-31), p. 711-
    Abstract: Constant interactions between tumor cells and the extracellular matrix (ECM) influence the progression of prostate cancer (PCa). One of the key components of the ECM are collagen fibers, since they are responsible for the tissue stiffness, growth, adhesion, proliferation, migration, invasion/metastasis, cell signaling, and immune recruitment of tumor cells. To explore this molecular marker in the content of PCa, we investigated two different tumor volumes (500 mm3 and 1000 mm3) of a xenograft mouse model of PCa with molecular magnetic resonance imaging (MRI) using a collagen-specific probe. For in vivo MRI evaluation, T1-weighted sequences before and after probe administration were analyzed. No significant signal difference between the two tumor volumes could be found. However, we detected a significant difference between the signal intensity of the peripheral tumor area and the central area of the tumor, at both 500 mm3 (p 〈 0.01, n = 16) and at 1000 mm3 (p 〈 0.01, n = 16). The results of our histologic analyses confirmed the in vivo studies: There was no significant difference in the amount of collagen between the two tumor volumes (p 〉 0.05), but within the tumor, higher collagen expression was observed in the peripheral area compared with the central area of the tumor. Laser ablation with inductively coupled plasma mass spectrometry further confirmed these results. The 1000 mm3 tumors contained 2.8 ± 1.0% collagen and the 500 mm3 tumors contained 3.2 ± 1.2% (n = 16). There was a strong correlation between the in vivo MRI data and the ex vivo histological data (y = −0.068x + 1.1; R2 = 0.74) (n = 16). The results of elemental analysis by inductively coupled plasma mass spectrometry supported the MRI data (y = 3.82x + 0.56; R2 = 0.79; n = 7). MRI with the collagen-specific probe in PCa enables differentiation between different tumor areas. This may help to differentiate tumor from healthy tissue, potentially identifying tumor areas with a specific tumor biology.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 3
    In: Biomedicines, MDPI AG, Vol. 9, No. 1 ( 2020-12-22), p. 1-
    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 of the tumor in a non-invasive examination. Furthermore, molecular probes could enable targeted therapies to suppress tumor growth or reduce the tumor size.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2720867-9
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 4
    In: Contrast Media & Molecular Imaging, Hindawi Limited, Vol. 2021 ( 2021-4-27), p. 1-9
    Abstract: Background. Currently, there is no reliable nonsurgical treatment for abdominal aortic aneurysm (AAA). This study, therefore, investigates if doxycycline reduces AAA growth and the number of rupture-related deaths in a murine ApoE−/− model of AAA and whether gadofosveset trisodium-based MRI differs between animals with and without doxycycline treatment. Methods. Nine ApoE−/− mice were implanted with osmotic minipumps continuously releasing angiotensin II and treated with doxycycline (30 mg/kg/d) in parallel. After four weeks, MRI was performed at 3T with a clinical dose of the albumin-binding probe gadofosveset (0.03 mmol/kg). Results were compared with previously published wild-type control animals and with previously studied ApoE−/− animals without doxycycline treatment. Differences in mortality were also investigated between these groups. Results. In a previous study, we found that approximately 25% of angiotensin II-infused ApoE−/− mice died, whereas in the present study, only one out of 9 angiotensin II-infused and doxycycline-treated ApoE−/− mice (11.1%) died within 4 weeks. Furthermore, doxycycline-treated ApoE−/− mice showed significantly lower contrast-to-noise (CNR) values ( p = 0.017 ) in MRI compared to ApoE−/− mice without doxycycline treatment. In vivo measurements of relative signal enhancement (CNR) correlated significantly with ex vivo measurements of albumin staining (R2 = 0.58). In addition, a strong visual colocalization of albumin-positive areas in the fluorescence albumin staining with gadolinium distribution in LA-ICP-MS was shown. However, no significant difference in aneurysm size was observed after doxycycline treatment. Conclusion. The present experimental in vivo study suggests that doxycycline treatment may reduce rupture-related deaths in AAA by slowing endothelial damage without reversing aneurysm growth.
    Type of Medium: Online Resource
    ISSN: 1555-4317 , 1555-4309
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2021
    detail.hit.zdb_id: 2222967-X
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 5
    In: Circulation: Cardiovascular Imaging, Ovid Technologies (Wolters Kluwer Health), Vol. 12, No. 3 ( 2019-03)
    Abstract: Molecular magnetic resonance imaging is a promising modality for the characterization of abdominal aortic aneurysms (AAAs). The combination of different molecular imaging biomarkers may improve the assessment of the risk of rupture. This study investigates the feasibility of imaging inflammatory activity and extracellular matrix degradation by concurrent dual-probe molecular magnetic resonance imaging in an AAA mouse model. Methods: Osmotic minipumps with a continuous infusion of Ang II (angiotensin II; 1000 ng/[kg·min]) to induce AAAs were implanted in apolipoprotein-deficient mice (N=58). Animals were assigned to 2 groups. In group 1 (longitudinal group, n=13), imaging was performed once after 1 week with a clinical dose of a macrophage-specific iron oxide–based probe (ferumoxytol, 4 mgFe/kg, surrogate marker for inflammatory activity) and an elastin-specific gadolinium-based probe (0.2 mmol/kg, surrogate marker for extracellular matrix degradation). Animals were then monitored with death as end point. In group 2 (week-by-week-group), imaging with both probes was performed after 1, 2, 3, and 4 weeks (n=9 per group). Both probes were evaluated in 1 magnetic resonance session. Results: The combined assessment of inflammatory activity and extracellular matrix degradation was the strongest predictor of AAA rupture (sensitivity 100%; specificity 89%; area under the curve, 0.99). Information from each single probe alone resulted in lower predictive accuracy. In vivo measurements for the elastin- and iron oxide–probe were in good agreement with ex vivo histopathology (Prussian blue-stain: R 2 =0.96, P 〈 0.001; Elastica van Giesson stain: R 2 =0.79, P 〈 0.001). Contrast-to-noise ratio measurements for the iron oxide and elastin-probe were in good agreement with inductively coupled mass spectroscopy ( R 2 =0.88, R 2 =0.75, P 〈 0.001) and laser ablation coupled to inductively coupled plasma–mass spectrometry. Conclusions: This study demonstrates the potential of the concurrent assessment of inflammatory activity and extracellular matrix degradation by dual-probe molecular magnetic resonance imaging in an AAA mouse model. Based on the combined information from both molecular probes, the rupture of AAAs could reliably be predicted.
    Type of Medium: Online Resource
    ISSN: 1941-9651 , 1942-0080
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
    detail.hit.zdb_id: 2440475-5
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 6
    In: Nature Communications, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2022-05-23)
    Abstract: The incidence of abdominal aortic aneurysms (AAAs) has substantially increased during the last 20 years and their rupture remains the third most common cause of sudden death in the cardiovascular field after myocardial infarction and stroke. The only established clinical parameter to assess AAAs is based on the aneurysm size. Novel biomarkers are needed to improve the assessment of the risk of rupture. ADAMTS4 (A Disintegrin And Metalloproteinase with ThromboSpondin motifs 4) is a strongly upregulated proteoglycan cleaving enzyme in the unstable course of AAAs. In the screening of a one-bead-one-compound library against ADAMTS4, a low-molecular-weight cyclic peptide is discovered with favorable properties for in vivo molecular magnetic resonance imaging applications. After identification and characterization, it’s potential is evaluated in an AAA mouse model. The ADAMTS4-specific probe enables the in vivo imaging-based prediction of aneurysm expansion and rupture.
    Type of Medium: Online Resource
    ISSN: 2041-1723
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2553671-0
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 7
    In: Cancers, MDPI AG, Vol. 14, No. 12 ( 2022-06-13), p. 2909-
    Abstract: Prostate cancer (PCa) is one of the most common cancers in men. For detection and diagnosis of PCa, non-invasive methods, including magnetic resonance imaging (MRI), can reduce the risk potential of surgical intervention. To explore the molecular characteristics of the tumor, we investigated the applicability of ferumoxytol in PCa in a xenograft mouse model in two different tumor volumes, 500 mm3 and 1000 mm3. Macrophages play a key role in tumor progression, and they are able to internalize iron-oxide particles, such as ferumoxytol. When evaluating T2*-weighted sequences on MRI, a significant decrease of signal intensity between pre- and post-contrast images for each tumor volume (n = 14; p 〈 0.001) was measured. We, furthermore, observed a higher signal loss for a tumor volume of 500 mm3 than for 1000 mm3. These findings were confirmed by histological examinations and laser ablation inductively coupled plasma-mass spectrometry. The 500 mm3 tumors had 1.5% iron content (n = 14; σ = 1.1), while the 1000 mm3 tumors contained only 0.4% iron (n = 14; σ = 0.2). In vivo MRI data demonstrated a correlation with the ex vivo data (R2 = 0.75). The results of elemental analysis by inductively coupled plasma-mass spectrometry correlated strongly with the MRI data (R2 = 0.83) (n = 4). Due to its long retention time in the blood, biodegradability, and low toxicity to patients, ferumoxytol has great potential as a contrast agent for visualization PCa.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527080-1
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 8
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 9, No. 1 ( 2019-09-25)
    Abstract: Molecular MRI is a promising in-vivo modality to detect and quantify morphological and molecular vessel-wall changes in atherosclerosis. The combination of different molecular biomarkers may improve the risk stratification of patients. This study aimed to investigate the feasibility of simultaneous visualization and quantification of plaque-burden and inflammatory activity by dual-probe molecular MRI in a mouse-model of progressive atherosclerosis and in response-to-therapy. Homozygous apolipoprotein E knockout mice (ApoE −/− ) were fed a high-fat-diet (HFD) for up to four-months prior to MRI of the brachiocephalic-artery. To assess response-to-therapy, a statin was administered for the same duration. MR imaging was performed before and after administration of an elastin-specific gadolinium-based and a macrophage-specific iron-oxide-based probe. Following in-vivo MRI, samples were analyzed using histology, immunohistochemistry, inductively-coupled-mass-spectrometry and laser-inductively-coupled-mass-spectrometry. In atherosclerotic-plaques, intraplaque expression of elastic-fibers and inflammatory activity were not directly linked. While the elastin-specific probe demonstrated the highest accumulation in advanced atherosclerotic-plaques after four-months of HFD, the iron-oxide-based probe showed highest accumulation in early atherosclerotic-plaques after two-months of HFD. In-vivo measurements for the elastin and iron-oxide-probe were in good agreement with ex-vivo histopathology (Elastica-van-Giesson stain: y = 298.2 + 5.8, R 2  = 0.83, p  〈  0.05; Perls‘ Prussian-blue-stain: y = 834.1 + 0.67, R 2  = 0.88, p  〈  0.05). Contrast-to-noise-ratio (CNR) measurements of the elastin probe were in good agreement with ICP-MS (y = 0.11x-11.3, R² = 0.73, p  〈  0.05). Late stage atherosclerotic-plaques displayed the strongest increase in both CNR and gadolinium concentration (p  〈  0.05). The gadolinium probe did not affect the visualization of the iron-oxide-probe and vice versa. This study demonstrates the feasibility of simultaneous assessment of plaque-burden and inflammatory activity by dual-probe molecular MRI of progressive atherosclerosis. The in-vivo detection and quantification of different MR biomarkers in a single scan could be useful to improve characterization of atherosclerotic-lesions.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2019
    detail.hit.zdb_id: 2615211-3
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 9
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2021-05-04)
    Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2615211-3
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 10
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2020-02-24)
    Abstract: Abdominal aortic aneurysm (AAA) remains a fatal disease. Its development encompasses a complex interplay between hemodynamic stimuli on and changes in the arterial wall. Currently available biomarkers fail to predict the risk of AAA rupture independent of aneurysm size. Therefore, novel biomarkers for AAA characterization are needed. In this study, we used a mouse model of AAA to investigate the potential of magnetic resonance imaging (MRI) with an albumin-binding probe to assess changes in vascular permeability at different stages of aneurysm growth. Two imaging studies were performed: a longitudinal study with follow-up and death as endpoint to predict rupture risk and a week-by-week study to characterize AAA development. AAAs, which eventually ruptured, demonstrated a significantly higher in vivo MR signal enhancement from the albumin-binding probe (p = 0.047) and a smaller nonenhancing thrombus area compared to intact AAAs (p = 0.001). The ratio of albumin-binding-probe enhancement of the aneurysm wall to size of nonenhancing-thrombus-area predicted AAA rupture with high sensitivity/specificity (100%/86%). More advanced aneurysms with higher vascular permeability demonstrated an increased uptake of the albumin-binding-probe. These results indicate that MRI with an albumin-binding probe may enable noninvasive assessment of vascular permeability in murine AAAs and prediction of rupture risk.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2615211-3
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. Further information can be found on the KOBV privacy pages