Correlation between Intraprostatic PSMA Uptake and MRI PI-RADS of [68Ga]Ga-PSMA-11 PET/MRI in Patients with Prostate Cancer: Comparison of PI-RADS Version 2.0 and PI-RADS Version 2.1

Purpose: We aimed to evaluate the correlation between PSMA uptake and magnetic resonance imaging (MRI) PI-RADS of simultaneous [68Ga]Ga-PSMA-11 PET/MRI regarding PI-RADS version 2.0 and 2.1 respectively and compared the difference between these two versions. Materials and methods: We retrospectively analyzed a total of forty-six patients with biopsy-proven prostate cancer who underwent simultaneous [68Ga]Ga-PSMA-11 PET/MRI. We classified the lesions regarding PI-RADS version 2.0 and 2.1, peripheral zone (PZ), and transitional zone (TZ), respectively. Based on regions of interest (ROI), standardized uptake values maximum (SUVmax), and corresponding lesion-to-background ratios (LBR) of SUVmax of each category, PI-RADS score 1 to 5, were measured. A comparison between PI-RADS version 2.0 and PI-RADS version 2.1 was performed. Results: A total of 215 focal prostate lesions were analyzed, including two subgroups, 125 TZ and 90 PZ. Data are reported as median and interquartile range (IQR). Regarding PI-RADS version 2.1, TZ SUVmax of each category were 1.5 (0.5, 1.9), 1.9 (0.8, 2.3), 3.3 (2.1, 4.6), 4.2 (3.1, 5.7), 7.3 (5.2, 9.7). PZ SUVmax of each category were 1.0 (0.8, 1.6), 2.5 (1.5, 3.2), 3.3 (1.9, 4.5), 4.3 (3.0, 5.4), 7.4 (5.0, 9.3). Regarding the inter-reader agreement of the overall PI-RADS assessment category, the kappa value was 0.723 for version 2.0 and 0.853 for version 2.1. Conclusion: Revisions of PI-RADS version 2.1 results in variations in lesions classification. Lesions with the PI-RADS category of 3, 4, and 5 present relatively higher intraprostatic PSMA uptake, while lesions with the PI-RADS category of 1 and 2 present relatively lower and similar uptake. Version 2.1 has higher inter-reader reproducibility than version 2.0

Molecular MR Imaging of Prostate Cancer

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

Iron Oxide Nanoparticles for Visualization of Prostate Cancer in MRI

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.SonderforschungsbereichDeutsche ForschungsgemeinschaftPeer Reviewe

Development and evaluation of novel imaging modalities for the characterization of abdominal aortic aneurysms in a mouse model

An abdominal aortic aneurysm (AAA) is defined as a permanent local dilatation of the abdominal aorta, usually accompanied by thrombus formation. Once ruptured, an AAA is associated with an overall mortality rate of over 90%. Even though AAAs represent one of the leading causes of sudden death in developed countries, the exact etiology and pathophysiology have not yet been fully elucidated. Nowadays, AAAs are clinically diagnosed by either computed tomography, ultrasound or magnetic resonance imaging (MRI), yet those modalities only deliver information on the aneurysm anatomy, size and form. It is generally accepted that AAA size correlates with the probability for rupture and related clinical events. However, a growing body of literature argues that the pathophysiology of AAA expansion is more multifaceted, with inflammation and degradation of the extracellular matrix (ECM) playing a pivotal role. Visualizing the complex nature of aneurysms requires the development of novel imaging modalities that facilitate more detailed depiction of AAAs. Magnetic resonance elastography (MRE) is an imaging technology that combines lowfrequency vibrations and MRI to create stiffness maps of body tissues. Remodeling of the ECM during AAA progression leads to stiffness changes, providing a potential imaging marker. Therefore, we assessed murine aneurysms by ex vivo microscopic multifrequency magnetic resonance elastography (μMMRE). By examining the aneurysmal thrombus, we discovered that regional variations in stiffness were strongly correlated to local histology-quantified ECM accumulation. With this proof-of-concept study, we demonstrated that MRE represents a suitable method for detecting shear wave speed changes reflected in varying stiffness values in the aneurysmal thrombus that in turn are representative of ECM remodeling. With successful clinical translation, this imaging modality could help detect potential fatal changes in the biomechanical structure of the AAA mimicked by ECM changes. Magnetic particle imaging (MPI) is an innovative imaging modality, enabling a highly sensitive detection of magnetic nanoparticles (MNPs). Since MNPs are a suitable surrogate marker for molecular targeting of macrophages and the aneurysmal development involves inflammation as a fundamental process, we tested the feasibility of imaging AAA inflammation with MPI. We demonstrated that the MNP accumulation in ex vivo murine aneurysms can be visualized and quantified with MPI. In addition, the colocalization of macrophages and MNPs was visible in histology. The ability to detect the spatial distribution and local concentration of MNPs establishes MPI as a promising tool for monitoring inflammatory progression in AAAs.Als abdominales Aortenaneurysma (AAA) beschreibt man eine permanente, lokale Dilatation des abdominellen Anteils der Aorta, meist begleitet von einer Thrombusbildung. Eine Ruptur endet in über 90% der Fälle tödlich. Auch wenn AAAs heutzutage eine der häufigsten Ursachen für einen plötzlichen Tod darstellen, ist die genaue Ätiologie und Pathophysiologie bis heute nicht eindeutig entschlüsselt. Die klinische Diagnose eines AAAs erfolgt heutzutage mittels Computertomographie, Ultraschall oder Magnetresonanztomographie (MRT), allerdings liefern die erwähnten Bildgebungsmodalitäten rein anatomische Informationen zu der Größe und Form des Aneurysmas. Im Allgemeinen wird angenommen, dass das Rupturrisiko mit der AAA Größe zusammenhängt. Mehrere Studien haben jedoch gezeigt, dass die Pathophysiologie der AAA Entwicklung facettenreich ist und dass Entzündung und Abbau der extrazellulären Matrix (EZM) eine zentrale Rolle spielen. Um die komplexe Natur des AAAs widerspiegeln zu können, benötigt man neuartige Bildgebungsmodalitäten, die einen detaillierten Einblick in die Biomechanik und Molekularbiologie ermöglichen. Die Magnetresonanzelastographie (MRE) ist eine neuartige Bildgebungsmethode, die auf die kombinierte Anwendung von MRT und die Erzeugung von mechanischen Wellen für die viskoelastische Charakterisierung von Geweben beruht. Der Umbau der extrazellulären Matrix stellt ein zentrales Geschehen in der Pathophysiologie des AAA Fortschritts dar. Aus diesem Grund haben wir die Machbarkeit von MRE als bildgebendes Verfahren für die Analyse von ex vivo AAAs von Mäusen untersucht. Durch den Einsatz von MRE für die Bildgebung von dem AAA Thrombus konnten wir regionale Unterschiede in der Wellengeschwindigkeit nachweisen, was wiederum für regional unterschiedliche Gewebesteifigkeit spricht. Diese Unterschiede korrelierten stark mit der lokalen Verteilung und Konzentration von extrazellulären Matrixproteinen. Eine zukünftige klinische Translation dieser Methode würde zu einer verbesserten Einschätzung der biomechanischen Eigenschaften des AAAs führen, welches eine verbesserte Risikoeinschätzung ermöglicht. Die Magnetpartikelbildgebung (MPI) stellt ebenso eine neuartige Bildgebungsmodalität dar. Dabei handelt es sich um die hochsensitive Detektion von magnetischen Nanopartikeln (MNPs) im Gewebe. MNPs stellen ein geeigneter indirekter Entzündungsmarker dar, da sie von Makrophagen am Ort des Entzündungsgeschehens aufgenommen werden. In unserer Studie haben wir die Umsetzbarkeit von MPI für die Bildgebung der Inflammation getestet. Wir konnten die MNP Akkumulation in den ex vivo AAA-Mausproben darstellen, sowie die Kolokalisation von MNPs mit Makrophagen in der Histologie. Aufgrund der hochquantitativen und örtlich aufgelösten Eisendarstellung gehört MPI zu den vielversprechendsten zukünftigen bildgebenden Verfahren für AAAs in der medizinischen Diagnostik

Dynamic Contrast-Enhanced MRI of Prostate Lesions of Simultaneous [68Ga]Ga-PSMA-11 PET/MRI: Comparison between Intraprostatic Lesions and Correlation between Perfusion Parameters

We aimed to retrospectively compare the perfusion parameters measured from dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) of prostate benign lesions and malignant lesions to determine the relationship between perfusion parameters. DCE-MRI was performed in patients with PCa who underwent simultaneous [68Ga]Ga-prostate-specific membrane antigen (PSMA)-11 positron emission tomography (PET)/MRI. Six perfusion parameters (arrival time (AT), time to peak (TTP), wash-in slope (W-in), wash-out slope (W-out), peak enhancement intensity (PEI), and initial area under the 60-s curve (iAUC)), and a semi-quantitative parameter, standardized uptake values maximum (SUVmax) were calculated by placing regions of interest in the largest area of the lesions. The DCE-MRI parameters between prostate benign and malignant lesions were compared. The DCE-MRI parameters in both the benign and malignant lesions subgroup with SUVmax ≤ 3.0 and SUVmax &gt; 3.0 were compared. The correlation of DCE-MRI parameters was investigated. Malignant lesions demonstrated significantly shorter TTP and higher SUVmax than did benign lesions. In the benign and malignant lesions subgroup, perfusion parameters of lesions with SUVmax ≤ 3.0 show no significant difference to those with SUVmax &gt; 3.0. DCE-MRI perfusion parameters show a close correlation with each other. DCE-MRI parameters reflect the perfusion characteristics of intraprostatic lesions with malignant lesions, demonstrating significantly shorter TTP. There is a moderate to strong correlation between DCE-MRI parameters. Semi-quantitative analysis reflects that malignant lesions show a significantly higher SUVmax than benign lesions

Dynamic Contrast-Enhanced MRI of Prostate Lesions of Simultaneous [68Ga]Ga-PSMA-11 PET/MRI: Comparison between Intraprostatic Lesions and Correlation between Perfusion Parameters

Simple Summary Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is an important method to analyze the perfusion model of tumors, allowing noninvasive quantification of microvascular structure and function. Furthermore, simultaneous [Ga-68]Ga-prostate-specific membrane antigen (PSMA)-11 positron emission tomography (PET)/MRI is currently the most advantageous way for assessing prostate cancer staging. Therefore, combining these two examinations helps to diagnose the lesions more comprehensively. Our study analyzes perfusion parameters between intraprostatic lesions and the correlation between perfusion parameters and [Ga-68]Ga-PSMA-11 PET. This study highlights the significant effect of PSMA uptake on perfusion parameters. Abstract We aimed to retrospectively compare the perfusion parameters measured from dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) of prostate benign lesions and malignant lesions to determine the relationship between perfusion parameters. DCE-MRI was performed in patients with PCa who underwent simultaneous [Ga-68]Ga-prostate-specific membrane antigen (PSMA)-11 positron emission tomography (PET)/MRI. Six perfusion parameters (arrival time (AT), time to peak (TTP), wash-in slope (W-in), wash-out slope (W-out), peak enhancement intensity (PEI), and initial area under the 60-s curve (iAUC)), and a semi-quantitative parameter, standardized uptake values maximum (SUVmax) were calculated by placing regions of interest in the largest area of the lesions. The DCE-MRI parameters between prostate benign and malignant lesions were compared. The DCE-MRI parameters in both the benign and malignant lesions subgroup with SUVmax 3.0 were compared. The correlation of DCE-MRI parameters was investigated. Malignant lesions demonstrated significantly shorter TTP and higher SUVmax than did benign lesions. In the benign and malignant lesions subgroup, perfusion parameters of lesions with SUVmax 3.0. DCE-MRI perfusion parameters show a close correlation with each other. DCE-MRI parameters reflect the perfusion characteristics of intraprostatic lesions with malignant lesions, demonstrating significantly shorter TTP. There is a moderate to strong correlation between DCE-MRI parameters. Semi-quantitative analysis reflects that malignant lesions show a significantly higher SUVmax than benign lesions

Assessment of Albumin ECM Accumulation and Inflammation as Novel In Vivo Diagnostic Targets for Multi-Target MR Imaging

Atherosclerosis is a progressive inflammatory vascular disease characterized by endothelial dysfunction and plaque burden. Extracellular matrix (ECM)-associated plasma proteins play an important role in disease development. Our magnetic resonance imaging (MRI) study investigates the feasibility of using two different molecular MRI probes for the simultaneous assessment of ECM-associated intraplaque albumin deposits caused by endothelial damage and progressive inflammation in atherosclerosis. Male apolipoprotein E-deficient (ApoE-/-)-mice were fed a high-fat diet (HFD) for 2 or 4 months. Another ApoE-/--group was treated with pravastatin and received a HFD for 4 months. T1- and T2*-weighted MRI was performed before and after albumin-specific MRI probe (gadofosveset) administration and a macrophage-specific contrast agent (ferumoxytol). Thereafter, laser ablation inductively coupled plasma mass spectrometry and histology were performed. With advancing atherosclerosis, albumin-based MRI signal enhancement and ferumoxytol-induced signal loss areas in T2*-weighted MRI increased. Significant correlations between contrast-to-noise-ratio (CNR) post-gadofosveset and albumin stain (R2 = 0.78, p < 0.05), and signal loss areas in T2*-weighted MRI with Perls’ Prussian blue stain (R2 = 0.83, p < 0.05) were observed. No interference of ferumoxytol with gadofosveset enhancement was detectable. Pravastatin led to decreased inflammation and intraplaque albumin. Multi-target MRI combining ferumoxytol and gadofosveset is a promising method to improve diagnosis and treatment monitoring in atherosclerosis.Peer Reviewe

Magnetic particle imaging of vascular inflammation in abdominal aortic aneurysm in murine model

Abdominal aortic aneurysm (AAAs) is a vascular disease, currently one of the leading causes of death in developed countries. Vascular inflammation plays a crucial role in the disease progression and substantially impacts many determinants in AAAs advancement. Superparamagnetic iron oxide nanoparticles (SPION) &nbsp;have been shown to be suitable agents for molecular targeting of vascular inflammation. The quantitative ability of MPI in mapping of SPION makes MPI a valid tool for monitoring of AAA progression. In this study, we examined the feasibility of MPI for imaging vascular inflammation in AAA in Angiotensin II-infused ApoE-/- mice with MPI suitable SPION, ferucarbotran (Resovist ®). The results were validated by histological analysis and magnetic particle spectroscopy (MPS)

Ex vivo magnetic particle imaging of vascular inflammation in abdominal aortic aneurysm in a murine model

Abdominal aortic aneurysms (AAAs) are currently one of the leading causes of death in developed countries. Inflammation is crucial in the disease progression, having a substantial impact on various determinants in AAAs development. Magnetic particle imaging (MPI) is an innovative imaging modality, enabling the highly sensitive detection of magnetic nanoparticles (MNPs), suitable as surrogate marker for molecular targeting of vascular inflammation. For this study, Apolipoprotein E-deficient-mice underwent surgical implantation of osmotic minipumps with constant Angiotensin II infusion. After 3 and 4 weeks respectively, in-vivo-magnetic resonance imaging (MRI), ex-vivo-MPI and ex-vivo-magnetic particle spectroscopy (MPS) were performed. The results were validated by histological analysis, immunohistology and laser ablation-inductively coupled plasma-mass spectrometry. MR-angiography enabled the visualization of aneurysmal development and dilatation in the experimental group. A close correlation (R = 0.87) with histological area assessment was measured. Ex-vivo-MPS revealed abundant iron deposits in AAA samples and ex-vivo histopathology measurements were in good agreement (R = 0.76). Ex-vivo-MPI and MPS results correlated greatly (R = 0.99). CD68-immunohistology stain and Perls’-Prussian-Blue-stain confirmed the colocalization of macrophages and MNPs. This study demonstrates the feasibility of ex-vivo-MPI for detecting inflammation in AAA. The quantitative ability for mapping MNPs establishes MPI as a promising tool for monitoring inflammatory progression in AAA in an experimental setting