Emerging methods in radiology.

Imaging modalities have developed rapidly in recent decades. In addition to improved resolution as well as whole-body and faster image acquisition, the possibilities of functional and molecular examination of tissue pathophysiology have had a decisive influence on imaging diagnostics and provided ground-breaking knowledge. Many promising approaches are currently being pursued to increase the application area of devices and contrast media and to improve their sensitivity and quantitative informative value. These are complemented by new methods of data processing, multiparametric data analysis, and integrated diagnostics. The aim of this article is to provide an overview of technological innovations that will enrich clinical imaging in the future, and to highlight the resultant diagnostic options. These relate to the established imaging methods such as CT, MRI, ultrasound, PET, and SPECT but also to new methods such as magnetic particle imaging (MPI), optical imaging, and photoacoustics. In addition, approaches to radiomic image evaluation are explained and the chances and difficulties for their broad clinical introduction are discussed. The potential of imaging to describe pathophysiological relationships in ever increasing detail, both at whole-body and tissue level, can in future be used to better understand the mechanistic effect of drugs, to preselect patients to therapies, and to improve monitoring of therapy success. Consequently, the use of interdisciplinary integrated diagnostics will greatly change and enrich the profession of radiologists.

Dual CTLA-4 and PD-L1 Blockade Inhibits Tumor Growth and Liver Metastasis in a Highly Aggressive Orthotopic Mouse Model of Colon Cancer.

Immune checkpoint inhibitors have shown clinical benefit in several cancer entities including metastatic microsatellite instable colorectal carcinomas. However, for the majority of metastatic colorectal carcinomas the potential and limitations of immune checkpoint inhibition is not fully understood. In this study, the effects of sole and dual CTLA-4 and PD-L1 blockade were investigated in a microsatellite stable highly aggressive orthotopic mouse model of colon cancer. Dual CTLA-4 and PD-L1 inhibition resulted in tumor growth stagnation and completely blocked liver metastasis. Sole CTLA-4 and PD-L1 inhibition only moderately reduced metastatic spread of the colon cancer cells, though CTLA-4 blockade being superior to PD-L1 inhibition. Dual immune checkpoint blockade and sole CTLA-4 inhibition significantly increased intratumoral CD8+ and CD4+ T cells and reduced FOXP3+/CD4+ Treg cells. This was associated with increased expression levels of the pro-inflammatory Th1/M1-related cytokines IFN-γ, IL-1α, IL-2, and IL-12. Moreover, tumors treated with combined immune checkpoint blockade showed the strongest increase in intratumoral iNOS+ macrophages, reduction of PD-L1+ and Tie2+ macrophages and the lowest expression of M2/Th2-related IL-4, TARC and COX-2. The assessment of further microenvironmental changes by DCE-MRI and immunohistology revealed no alterations in functional tumor vascularization upon combined immune checkpoint blockade, but a significant increase in intratumoral fibroblasts and collagen I deposition. Thus, the synergistic inhibitory effects of dual immune checkpoint inhibition can be explained by anti-tumorigenic T cell responses mediated by CTLA-4 inhibition and M1 macrophage polarization predominantly induced by PD-L1 blockade. This was accompanied by pronounced fibroblast activation highlighting the interconnection between immunogenicity and desmoplasia.

Bone regeneration induced by a 3D architectured hydrogel in a rat critical-size calvarial defect.

Bone regeneration can be stimulated by implantation of biomaterials, which is especially important for larger bone defects. Here, healing potency of the porous ArcGel was evaluated in a critical-size calvarial bone defect in rats in comparison with clinical standard autologous bone and Bio-Oss® Collagen (BioOss), a bone graft material frequently used in clinics. Bone healing and metabolic processes involved were monitored longitudinally by [18F]-fluoride and [18F]-FDG µ-PET/CT 1d, 3d, 3w, 6w, and 12w post implantation. Differences in quality of bone healing were assessed by ex vivo µ-CT, mechanical tests and histomorphometry. The amount of bone formed after implantation of ArcGel was comparable to autologous bone and superior to BioOss (histomorphometry). Furthermore, microarchitecture of newly formed bone was more physiological and better functional in case of ArcGel (push-out tests). [18F]-FDG uptake increased until 3d after implantation, and decreased until 12w for both ArcGel and BioOss. [18F]-fluoride uptake increased until 3w post implantation for all materials, but persisted significantly longer at higher levels for BioOss, which indicates a prolonged remodelling phase. The study demonstrates the potential of ArcGel to induce restitutio ad integrum comparable with clinical standard autologous bone and better bone regeneration in large defects compared to a commercial state-of-the-art biomaterial.

Longitudinal imaging of the ageing mouse.

Several non-invasive imaging techniques are used to investigate the effect of pathologies and treatments over time in mouse models. Each preclinical in vivo technique provides longitudinal and quantitative measurements of changes in tissues and organs, which are fundamental for the evaluation of alterations in phenotype due to pathologies, interventions and treatments. However, it is still unclear how these imaging modalities can be used to study ageing with mice models. Almost all age related pathologies in mice such as osteoporosis, arthritis, diabetes, cancer, thrombi, dementia, to name a few, can be imaged in vivo by at least one longitudinal imaging modality. These measurements are the basis for quantification of treatment effects in the development phase of a novel treatment prior to its clinical testing. Furthermore, the non-invasive nature of such investigations allows the assessment of different tissue and organ phenotypes in the same animal and over time, providing the opportunity to study the dysfunction of multiple tissues associated with the ageing process. This review paper aims to provide an overview of the applications of the most commonly used in vivo imaging modalities used in mouse studies: micro-computed-tomography, preclinical magnetic-resonance-imaging, preclinical positron-emission-tomography, preclinical single photon emission computed tomography, ultrasound, intravital microscopy, and whole body optical imaging.

[Molecular ultrasound imaging: Clinical applications]. / Molekulare Ultraschallbildgebung: Chancen für die Klinik.

BACKGROUND: Contrast-enhanced ultrasound imaging is increasingly being used in clinical applications, particularly for cardiovascular and liver diagnostics. In this context the availability of new molecular contrast agents and the initiation of clinical translation promises new options for pathomechanistic diagnostics. MATERIAL AND METHODS: Analysis of the current literature on the development of molecular ultrasound contrast agents, the detection methods as well as the applications in preclinical and clinical studies. RESULTS: Molecular contrast agents have become established in preclinical research for the detection of inflammation and angiogenesis and have been continuously refined over recent years. They consist of gas filled microbubbles with a diameter of 1-5 µm and the gas core is stabilized by a shell made of lipids, proteins or polymers to which biomolecules are conjugated that determine the target specificity. The agent BR55 is the first clinically evaluated molecular ultrasound contrast agent. It binds to the angiogenesis marker vascular endothelial growth factor receptor 2 (VEGFR2) and has been studied in several preclinical and clinical phase I and II studies on tumor diagnostics and characterization. CONCLUSION: Molecular ultrasound imaging is rapidly evolving in preclinical research for a broad field of applications. Translation to clinical practice is conceivable for many indications and is already ongoing for BR55.

Applications of nanoparticles for diagnosis and therapy of cancer.

During the last decades, a plethora of nanoparticles have been developed and evaluated and a real hype has been created around their potential application as diagnostic and therapeutic agents. Despite their suggestion as potential diagnostic agents, only a single diagnostic nanoparticle formulation, namely iron oxide nanoparticles, has found its way into clinical routine so far. This fact is primarily due to difficulties in achieving appropriate pharmacokinetic properties and a reproducible synthesis of monodispersed nanoparticles. Furthermore, concerns exist about their biodegradation, elimination and toxicity. The majority of nanoparticle formulations that are currently routinely used in the clinic are used for therapeutic purposes. These therapeutic nanoparticles aim to more efficiently deliver a (chemo-) therapeutic drug to the pathological site, while avoiding its accumulation in healthy organs and tissues, and are predominantly based on the "enhanced permeability and retention" (EPR) effect. Furthermore, based on their ability to integrate diagnostic and therapeutic entities within a single nanoparticle formulation, nanoparticles hold great promise for theranostic purposes and are considered to be highly useful for personalizing nanomedicine-based treatments. In this review article, we present applications of diagnostic and therapeutic nanoparticles, summarize frequently used non-invasive imaging techniques and describe the role of EPR in the accumulation of nanotheranostic formulations. In this context, the clinical potential of nanotheranostics and image-guided drug delivery for individualized and improved (chemo-) therapeutic interventions is addressed.

Formulation and characterization of microspheres loaded with imatinib for sustained delivery.

The aim of this study was the development of imatinib-loaded poly(d,l-lactide-co-glycolide) (PLGA) microspheres with high loading efficiency which can afford continuous release of imatinib over a prolonged period of time. Imatinib mesylate loaded PLGA microspheres with a size of 6-20 µm were prepared by a double emulsion (W1/O/W2) method using dichloromethane as volatile solvent. It was found that the microspheres were spherical with a non-porous surface; imatinib loading efficiency (LE) was highly dependent on the pH of the external water phase (W2). By increasing the pH of W2 phase above the highest pKa of imatinib (pKa 8.1), at which imatinib is mainly uncharged, the LE increased from 10% to 90% (pH 5.0 versus pH 9.0). Conversely, only 4% of its counter ion, mesylate, was retained in the microspheres at the same condition (pH 9.0). Since mesylate is highly water soluble, it is unlikely that it partitions into the organic phase. We demonstrated, using differential scanning calorimetry (DSC), that imatinib was molecularly dispersed in the polymeric matrix at loadings up to 8.0%. At higher drug loading, imatinib partially crystallized in the matrix. Imatinib microspheres released their cargo during three months by a combination of diffusion through the polymer matrix and polymer erosion. In conclusion, we have formulated imatinib microspheres with high LE and LC. Although we started with a double emulsion of imatinib mesylate, the obtained microspheres contained imatinib base which was mainly molecularly dispersed in the polymer matrix. These microspheres release imatinib over a 3-month period which is of interest for local treatment of cancer.

Sunitinib microspheres based on [PDLLA-PEG-PDLLA]-b-PLLA multi-block copolymers for ocular drug delivery.

Sunitinib is a multi-targeted receptor tyrosine kinase (RTK) inhibitor that blocks several angiogenesis related pathways. The aim of this study was to develop sunitinib-loaded polymeric microspheres that can be used as intravitreal formulation for the treatment of ocular diseases. A series of novel multi-block copolymers composed of amorphous blocks of poly-(D,L-lactide) (PDLLA) and polyethylene glycol (PEG) and of semi-crystalline poly-(L-lactide) (PLLA) blocks were synthesized. Sunitinib-loaded microspheres were prepared by a single emulsion method using dichloromethane as volatile solvent and DMSO as co-solvent. SEM images showed that the prepared microspheres (∼ 30 µm) were spherical with a non-porous surface. Sunitinib-loaded microspheres were studied for their degradation and in-vitro release behavior. It was found that increasing the percentage of amorphous soft blocks from 10% to 30% accelerated the degradation of the multi-block copolymers. Sunitinib microspheres released their cargo for a period of at least 210 days by a combination of diffusion and polymer erosion. The initial burst (release in 24h) and release rate could be tailored by controlling the PEG-content of the multi-block copolymers. Sunitinib-loaded microspheres suppressed angiogenesis in a chicken chorioallantoic membrane (CAM) assay. These microspheres therefore hold promise for long-term suppression of ocular neovascularization.

MR-compatibility assessment of the first preclinical PET-MRI insert equipped with digital silicon photomultipliers.

PET (positron emission tomography) with its high sensitivity in combination with MRI (magnetic resonance imaging) providing anatomic information with good soft-tissue contrast is considered to be a promising hybrid imaging modality. However, the integration of a PET detector into an MRI system is a challenging task since the MRI system is a sensitive device for external disturbances and provides a harsh environment for electronic devices. Consequently, the PET detector has to be transparent for the MRI system and insensitive to electromagnetic disturbances. Due to the variety of MRI protocols imposing a wide range of requirements regarding the MR-compatibility, an extensive study is mandatory to reliably assess worst-case interference phenomena between the PET detector and the MRI scanner. We have built the first preclinical PET insert, designed for a clinical 3 T MRI, using digital silicon photomultipliers (digital SiPM, type DPC 3200-22, Philips Digital Photon Counting). Since no thorough interference investigation with this new digital sensor has been reported so far, we present in this work such a comprehensive MR-compatibility study. Acceptable distortion of the B0 field homogeneity (volume RMS = 0.08 ppm, peak-to-peak value = 0.71 ppm) has been found for the PET detector installed. The signal-to-noise ratio degradation stays between 2-15% for activities up to 21 MBq. Ghosting artifacts were only found for demanding EPI (echo planar imaging) sequences with read-out gradients in Z direction caused by additional eddy currents originated from the PET detector. On the PET side, interference mainly between the gradient system and the PET detector occurred: extreme gradient tests were executed using synthetic sequences with triangular pulse shape and maximum slew rate. Under this condition, a relative degradation of the energy (⩽10%) and timing (⩽15%) resolution was noticed. However, barely measurable performance deterioration occurred when morphological MRI protocols are conducted certifying that the overall PET performance parameters remain unharmed.

In vitro, in vivo and in silico analysis of the anticancer and estrogen-like activity of guava leaf extracts.

Anticancer drug research based on natural compounds enabled the discovery of many drugs currently used in cancer therapy. Here, we report the in vitro, in vivo and in silico anticancer and estrogen-like activity of Psidium guajava L. (guava) extracts and enriched mixture containing the meroterpenes guajadial, psidial A and psiguadial A and B. All samples were evaluated in vitro for anticancer activity against nine human cancer lines: K562 (leukemia), MCF7 (breast), NCI/ADR-RES (resistant ovarian cancer), NCI-H460 (lung), UACC-62 (melanoma), PC-3 (prostate), HT-29 (colon), OVCAR-3 (ovarian) and 786-0 (kidney). Psidium guajava's active compounds displayed similar physicochemical properties to estradiol and tamoxifen, as in silico molecular docking studies demonstrated that they fit into the estrogen receptors (ERs). The meroterpene-enriched fraction was also evaluated in vivo in a Solid Ehrlich murine breast adenocarcinoma model, and showed to be highly effective in inhibiting tumor growth, also demonstrating uterus increase in comparison to negative controls. The ability of guajadial, psidial A and psiguadials A and B to reduce tumor growth and stimulate uterus proliferation, as well as their in silico docking similarity to tamoxifen, suggest that these compounds may act as Selective Estrogen Receptors Modulators (SERMs), therefore holding significant potential for anticancer therapy.

Imaging in the age of molecular medicine: monitoring of anti-angiogenic treatments.

Angiogenesis is a complex multistep process and a crucial pre-requisite for tumor growth, invasion and metastasis. A profound knowledge of the mechanisms including the elucidation of markers for angiogenic vessels is essential for the generation of new anti-angiogenic chemotherapeutic agents and the improvement of specific imaging techniques. During the last decades, numerous angiogenesis inhibitors have been developed and some of them have shown promising results in preclinical and clinical trials. However, the response to anti-angiogenic treatment is often delayed and shows high inter-individual variations. In order to improve anti-angiogenic therapy, new specific surrogate markers are necessary that allow the characterization of different angiogenic steps, especially at the early stage. In this respect, non-invasive imaging is a potent tool for characterizing the tumor vascularization and for sensitive and longitudinal treatment monitoring. In particular, new molecular imaging techniques might ultimately improve the characterization of the angiogenic tumor phenotype and stage. This review summarizes the current status of different imaging modalities e.g. MRI, CT, US, nuclear and optical imaging with respect to the imaging of tumor angiogenesis and of anti-angiogenic treatments. It also includes new approaches in molecular imaging, which give deep insight into the tumor stage and the response of tumor vessels to anti-angiogenic therapy. Thus, this may lead to a more personalized cancer therapy in future.

Optimized RF shielding techniques for simultaneous PET/MR.

PURPOSE: Integration of positron emission tomography (PET) and magnetic resonance (MR) in a merged device requires shielding of the PET detector electronics. The authors demonstrate that a multiple shell setup exhibits advantages over a single shell shielding enclosure. METHODS: A spherical shell model is used to derive analytical results. Numerical computations of the electromagnetic fields with a commercial software package (FEKO) and experiments are used to confirm our findings. RESULTS: Replacing a single shell enclosure by a multilayer approach barely changes its behavior toward low frequency magnetic fields (MR gradient fields), while improving shielding at high frequencies (proton resonant frequency) by orders of magnitude. CONCLUSIONS: For a given required shielding factor at the proton resonant frequency, the eddy currents induced by the MR gradient fields may be reduced by employing a multiple shell setup.

Fully automated intrinsic respiratory and cardiac gating for small animal CT.

A fully automated, intrinsic gating algorithm for small animal cone-beam CT is described and evaluated. A parameter representing the organ motion, derived from the raw projection images, is used for both cardiac and respiratory gating. The proposed algorithm makes it possible to reconstruct motion-corrected still images as well as to generate four-dimensional (4D) datasets representing the cardiac and pulmonary anatomy of free-breathing animals without the use of electrocardiogram (ECG) or respiratory sensors. Variation analysis of projections from several rotations is used to place a region of interest (ROI) on the diaphragm. The ROI is cranially extended to include the heart. The centre of mass (COM) variation within this ROI, the filtered frequency response and the local maxima are used to derive a binary motion-gating parameter for phase-sensitive gated reconstruction. This algorithm was implemented on a flat-panel-based cone-beam CT scanner and evaluated using a moving phantom and animal scans (seven rats and eight mice). Volumes were determined using a semiautomatic segmentation. In all cases robust gating signals could be obtained. The maximum volume error in phantom studies was less than 6%. By utilizing extrinsic gating via externally placed cardiac and respiratory sensors, the functional parameters (e.g. cardiac ejection fraction) and image quality were equivalent to this current gold standard. This algorithm obviates the necessity of both gating hardware and user interaction. The simplicity of the proposed algorithm enables adoption in a wide range of small animal cone-beam CT scanners.

[Molecular imaging in oncology using targeted ultrasound contrast agents]. / Molekulare Bildgebung in der Onkologie: Tumor-spezifische Ultraschallkontrastmittel.

Molecular imaging enables to assess disease-associated processes at the cellular and molecular level. Nuclear medicine techniques are already available in the clinical routine. Besides these techniques, intensive research has been performed in the field of ultrasound. The development of target-specific ultrasound contrast agents in combination with modern imaging systems transformed ultrasound to a capable molecular imaging technique. It has been shown that the expression of disease-associated endothelial receptors can be assessed using targeted microbubbles, demonstrating its high value in the diagnosis of several diseases. The broad availability of suitable ultrasound systems promises a wide utilisation in the clinical routine, once clinically approved contrast agents are available. This review summarizes the basics and the current status of molecular ultrasound imaging.

Functional and molecular ultrasound imaging: concepts and contrast agents.

Contrast-enhanced ultrasound has shown convincing results for monitoring vessel morphology, surrogate markers of vascularization and changes in molecular marker expression in oncological and cardiovascular diseases. Ultrasound contrast agents have the ability to increase the backscattering signal intensity of an ultrasound pulse. An interesting class of ultrasound contrast agents are gas filled microbubbles, which can be synthesized by external bubble encapsulation using sugar matrices or microspheres consisting of lipids or polymers with or without surfactant and by selecting gases with low blood solubility and diffusion coefficient such as perfluorocarbons or sulphur hexafluoride. Ultrasound contrast agents can be classified according to the rigidity of their shell. Soft-shell microbubbles are coated with a thin monolayer of surfactant molecules such as palmitic acid or phospholipids and are very sensitive to pressure changes. Hard-shell microbubbles have a rigid shell made of polymers such as polycyanoacrylate, which dramatically increases their stability. Depending on the acoustic properties of the microbubbles and on the purpose of the examination either destructive or non destructive methods are preferred for their detection. Microbubbles can be detected by destructive and non-destructive methods. Both soft- and hard-shell microbubbles coated with target-specific molecules can also be used for molecular imaging. Using target-specific approaches, the expression of several angiogenic markers such as VEGFR2, alphavbeta3 Integrins, ICAM, and E-selectin has been investigated in neoplastic and vascular diseases. This article summarizes the synthesis and properties of contrast agents as well as the indications, limitations and future potential of contrast-enhanced functional and molecular ultrasound.

TNF-alpha and the IFN-gamma-inducible protein 10 (IP-10/CXCL-10) delivered by parvoviral vectors act in synergy to induce antitumor effects in mouse glioblastoma.

Interferon-gamma-inducible protein 10 is a potent chemoattractant for natural killer cells and activated T lymphocytes. It also displays angiostatic properties and some antitumor activity. Tumor necrosis factor-alpha (TNF-alpha) is a powerful immunomodulating cytokine with demonstrated tumoricidal activity in various tumor models and the ability to induce strong immune responses. This prompted us to evaluate the antitumor effects of recombinant parvoviruses designed to deliver IP-10 or TNF-alpha into a glioblastoma. When Gl261 murine glioma cells were infected in vitro with an IP-10- or TNF-alpha-transducing parvoviral vector and were subcutaneously implanted in mice, tumor growth was significantly delayed. Complete tumor regression was observed when the glioma cells were coinfected with both the vectors, demonstrating synergistic antitumor activity. In an established in vivo glioma model, however, repeated simultaneous peritumoral injection of the IP-10- and TNF-alpha-delivering parvoviruses failed to improve the therapeutic effect as compared with the use of a single cytokine-delivering vector. In this tumor model, cytokine-mediated immunostimulation, rather than inhibition of vascularization, is likely responsible for the therapeutic efficacy.

Image-guided and passively tumour-targeted polymeric nanomedicines for radiochemotherapy.

Drug targeting systems are nanometer-sized carrier materials designed for improving the biodistribution of systemically applied (chemo-) therapeutics. Reasoning that (I) the temporal and spatial interaction between systemically applied chemotherapy and clinically relevant fractionated radiotherapy is suboptimal, and that (II) drug targeting systems are able to improve the temporal and spatial parameters of this interaction, we have here set out to evaluate the potential of 'carrier-based radiochemotherapy'. N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers were used as a model drug targeting system, doxorubicin and gemcitabine as model drugs, and the syngeneic and radio- and chemoresistant Dunning AT1 rat prostate carcinoma as a model tumour model. Using magnetic resonance imaging and gamma-scintigraphy, the polymeric drug carriers were first shown to circulate for prolonged periods of time, to localise to tumours both effectively and selectively, and to improve the tumour-directed delivery of low molecular weight agents. Subsequently, they were then shown to interact synergistically with radiotherapy, with radiotherapy increasing the tumour accumulation of the copolymers, and with the copolymers increasing the therapeutic index of radiochemotherapy (both for doxorubicin and for gemcitabine). Based on these findings, and on the fact that its principles are likely broadly applicable, we propose carrier-based radiochemotherapy as a novel concept for treating advanced solid malignancies.

Initial Experience with a Novel Low-Dose Micro-CT System.

PURPOSE: Investigation of the hardware and image characteristics of a novel micro-CT system and evaluation of its potential to image animals and tissue samples. MATERIALS AND METHODS: The scanner was characterized by phantom studies regarding image homogeneity, CT number stability, soft-tissue contrast, spatial resolution and X-ray dose. The phantoms used were specially designed to evaluate the imaging of mice and rats. Scans of hearts with coronary stents were performed and the tissue morphology and vascularization of tumor-bearing rodents were studied with dynamic contrast-enhanced (DCE) CT. RESULTS: The CT numbers of the acrylic phantoms were reproducible with a 4 HU deviation. The inter-pixel deviation was low but depended on the scan mode. The correlation coefficient between CT number and iodine concentration (0 - 6000 HU) was 0.99. Single wires, lumen and endo-luminal plaques of heart stents were distinguishable. The density-time courses were reliably recorded and made it possible to distinguish the tumor and muscle tissue in DCE micro-CT scans CONCLUSION: The novel micro-CT scanner is suitable for studying tissue densities and contrast agent kinetics.

Contrast agents and applications to assess tumor angiogenesis in vivo by magnetic resonance imaging.

Angiogenesis plays a key role in the development of cancer and is precondition for tumor growth, invasion and spread. Therefore, numerous angiogenesis inhibitors have been developed, of which some show potential to defeat cancer in preclinical and clinical trials. However, response to antiangiogenic treatments is often delayed and marked by high interindividual variability making a closely mashed and efficient observation of the patient necessary. Therefore, surrogate markers which specifically catch early response to tumor therapy are highly desirable. Functional parameters like relative blood volume, perfusion and vessel permeability can be assessed using T(1) and T(2)*-weighted dynamic contrast-enhanced (DCE) MRI. Various reports are available on this topic but results are controversial. During antiangiogenic therapies some authors describe pronounced changes in blood volume: others find effects only on vessel permeability or perfusion. These conflictive observations can be attributed to the different tumor models, therapies, measurement techniques and contrast agents (CA). Particularly the choice of the optimal CA is considered to be essential for a successful characterization of tumor angiogenesis. Often therapy effects on vessel permeability only become apparent, when blood pool CA are used. This article reviews the current state of DCE and molecular MRI of angiogenesis. Besides a general introduction of the different measurement and postprocessing methods and its previous applications, design, structure and use of different types of CA are the main focus of this article.

An optimized workflow for the integration of biological information into radiotherapy planning: experiences with T1w DCE-MRI.

Planning of radiotherapy is often difficult due to restrictions on morphological images. New imaging techniques enable the integration of biological information into treatment planning and help to improve the detection of vital and aggressive tumour areas. This might improve clinical outcome. However, nowadays morphological data sets are still the gold standard in the planning of radiotherapy. In this paper, we introduce an in-house software platform enabling us to combine images from different imaging modalities yielding biological and morphological information in a workflow driven approach. This is demonstrated for the combination of morphological CT, MRI, functional DCE-MRI and PET data. Data of patients with a tumour of the prostate and with a meningioma were examined with DCE-MRI by applying pharmacokinetic two-compartment models for post-processing. The results were compared with the clinical plans for radiation therapy. Generated parameter maps give additional information about tumour spread, which can be incorporated in the definition of safety margins.