Simultaneous assessment of vessel size index, relative blood volume, and vessel permeability in a mouse brain tumor model using a combined spin echo gradient echo echo-planar imaging sequence and viable tumor analysis.

Purpose: Combining multiple imaging biomarkers in one magnetic resonance imaging (MRI) session would be beneficial to gain more data pertaining to tumor vasculature under therapy. Therefore, simultaneous measurement of perfusion, permeability, and vessel size imaging (VSI) using a gradient echo spin echo (GE-SE) sequence with injection of a clinically approved gadolinium (Gd)-based contrast agent was assessed in an orthotopic glioma model.

Materials And Methods: A combined spin echo gradient echo echo-planar imaging sequence was implemented using a single contrast agent Gd diethylenetriaminepentaacetic acid (Gd-DTPA).

Safety of hybrid electrodes for single-neuron recordings in humans.

Background: Intracranial in vivo recordings of individual neurons in humans are increasingly performed for a better understanding of the mechanisms of epileptogenesis and of the neurobiological basis of cognition. So far, information about the safety of stereotactic implantations and of magnetic resonance imaging (MRI) with hybrid depth electrodes is scarce.

Objective: The aim of this study was to assess neurosurgical safety of implantations, recordings, and imaging using hybrid electrodes in humans.

Dental MRI: imaging of soft and solid components without ionizing radiation.

Purpose: To evaluate the ability of conventional and ultra-short or zero echo time MRI for imaging of soft and solid dental components in and ex vivo.

Materials And Methods: Turbo spin echo (TSE), ultra-short echo time (UTE), and zero echo time (ZTE) MRI were performed on extracted (human and equine) teeth and in vivo using whole-body and small-bore MR systems at 3 T, 7T, and 9.4T, respectively.

On impulse response functions computed from dynamic contrast-enhanced image data by algebraic deconvolution and compartmental modeling.

Concentration-time courses measured by dynamic contrast-enhanced (DCE) imaging can be described by a convolution of the arterial input with an impulse response function, Q(T)(t), characterizing tissue microcirculation. Data analysis is based on two different approaches: computation of Q(T)(t) by algebraic deconvolution (AD) and subsequent evaluation according to the indicator dilution theory (IDT) or parameterization of Q(T)(t) by analytical expressions derived by compartmental modeling. Pitfalls of both strategies will be addressed in this study.

Sorafenib tosylate and paclitaxel induce anti-angiogenic, anti-tumour and anti-resorptive effects in experimental breast cancer bone metastases.

Purpose: In this study we investigated sorafenib tosylate and paclitaxel as single and combination therapies regarding their effects on tumour growth and vasculature as well as their potency to inhibit osteolysis in experimental breast cancer bone metastases.

Experimental Design: Nude rats bearing breast cancer bone metastases were treated with sorafenib tosylate (7 mg/kg, n=11), paclitaxel (5mg/kg, n=11) or the combination of both (n=10) and were compared to untreated controls (n=11). In a longitudinal study, volumes of osteolyses and respective soft tissue tumours were measured in these groups by MRI and volume CT, while changes in cellularity within bone metastases were assessed by diffusion-weighted imaging.

Drug-induced vessel remodeling in bone metastases as assessed by dynamic contrast enhanced magnetic resonance imaging and vessel size imaging: a longitudinal in vivo study.

Purpose: The aim of this study was to assess the antiangiogenic treatment effects of zoledronic acid (ZA) and sunitinib malate (SM) noninvasively in experimental breast cancer bone metastases by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and vessel size imaging.

Experimental Design: Nude rats bearing bone metastases after inoculation of MDA-MB-231 breast cancer cells were treated with ZA (40 microg/kg weekly; n = 8 rats), SM (20 mg/kg daily; n = 8 rats), or their combination (ZA and SM; n = 8 rats) and compared with sham-treated controls (n = 10 rats). Vascular changes in bone metastases were longitudinally imaged in vivo using DCE-MRI [amplitude (A) and exchange rate coefficient (k(ep))] and vessel size imaging [blood volume (BV) and vessel size index (VI)].

Estimation of tissue perfusion by dynamic contrast-enhanced imaging: simulation-based evaluation of the steepest slope method.

Objective: Tissue perfusion is frequently determined from dynamic contrast-enhanced CT or MRI image series by means of the steepest slope method. It was thus the aim of this study to systematically evaluate the reliability of this analysis method on the basis of simulated tissue curves.

Methods: 9600 tissue curves were simulated for four noise levels, three sampling intervals and a wide range of physiological parameters using an axially distributed reference model and subsequently analysed by the steepest slope method.

MMP inhibition blocks fibroblast-dependent skin cancer invasion, reduces vascularization and alters VEGF-A and PDGF-BB expression.

Tumor invasion requires intense interactions with stromal cells and a profound extracellular matrix remodelling by matrix metalloproteinases (MMPs). Here, we assessed the specific contribution of fibroblasts to tumor invasion, MMPs, tissue inhibitors of MMPs and angiogenesis-related cytokine expression in organotypic cultures of highly malignant HaCaT-ras A-5RT3 cells, with and without MMP inhibition. Collagen degradation, the hallmark of tumor invasion, was dependent on fibroblasts and active MMP-2.

Platelet-derived growth factor-B normalizes micromorphology and vessel function in vascular endothelial growth factor-A-induced squamous cell carcinomas.

Vascular endothelial growth factor (VEGF), which is a key regulator of angiogenesis, often induces formation of immature vessels with increased permeability and reduced vessel functionality. Here, we demonstrate that de novo expression of murine (m)VEGF-164 induces malignant and invasive tumor growth of HaCaT keratinocytes. However, the mVEGF-164-induced tumors are ulcerated with a disorganized epithelium that is interrupted by lacunae with limited basement membrane and endothelial cell coverage.

RGD-labeled USPIO inhibits adhesion and endocytotic activity of alpha v beta3-integrin-expressing glioma cells and only accumulates in the vascular tumor compartment.

Purpose: To investigate the biologic effect of arginine-glycine-aspartic acid (RGD)-labeled ultrasmall superparamagnetic iron oxide (USPIO) (referred to as RGD-USPIO) on human umbilical vein endothelial cells (HUVECs), ovarian carcinoma (MLS) cells, and glioblastoma (U87MG) cells and on U87MG xenografts in vivo.

Materials And Methods: All experiments were approved by the governmental review committee on animal care.USPIOs were coated with integrin-specific (RGD) or unspecific (arginine-alanine-aspartic acid [RAD]) peptides.

Simulation-based comparison of two approaches frequently used for dynamic contrast-enhanced MRI.

The purpose was to compare two approaches for the acquisition and analysis of dynamic-contrast-enhanced MRI data with respect to differences in the modelling of the arterial input-function (AIF), the dependency of the model parameters on physiological parameters and their numerical stability. Eight hundred tissue concentration curves were simulated for different combinations of perfusion, permeability, interstitial volume and plasma volume based on two measured AIFs and analysed according to the two commonly used approaches. The transfer constants (Approach 1) K (trans) and (Approach 2) k (ep) were correlated with all tissue parameters.

Pharmacokinetic analysis of tissue microcirculation using nested models: multimodel inference and parameter identifiability.

The purpose of this study is to evaluate the identifiability of physiological tissue parameters by pharmacokinetic modeling of concentration-time curves derived under conditions that are realistic for dynamic-contrast-enhanced (DCE) imaging and to assess the information-theoretic approach of multimodel inference using nested models. Tissue curves with a realistic noise level were simulated by means of an axially distributed multipath reference model using typical values reported in literature on plasma flow, permeability-surface area product, and volume fractions of the intravascular and interstitial space. The simulated curves were subsequently analyzed by a two-compartment model containing these physiological quantities as fit parameters as well as by two reduced models with only three and two parameters formulated for the case of a permeability-limited and a flow-limited scenario, respectively.

Tumor perfusion assessed by dynamic contrast-enhanced MRI correlates to the grading of renal cell carcinoma: initial results.

In this study, we investigated whether assessment of the tumor perfusion by dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) enables to estimate the morphologic grading of renal cell carcinomas. A total of 21 patients with suspected renal cell cancer were examined using a Gadobutrol-enhanced, dynamic saturation-recovery, turbo-fast, low-angle shot sequence. Tumor perfusion and the tissue-blood ratio within the entire tumor and the most highly vascularized part of the tumor were calculated according to the model of Miles.

Assessment of vascular remodeling under antiangiogenic therapy using DCE-MRI and vessel size imaging.

Purpose: To assess vascular remodeling in tumors during two different antiangiogenic therapies with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and vessel size imaging and to evaluate the vessel size index (VSI) as a novel biomarker of therapy response.

Materials And Methods: In two independent experiments, nude mice bearing human skin squamous cell carcinoma xenografts were treated with a vascular endothelial growth factor (VEGF) inhibitor (bevacizumab) or a multitargeted tyrosine kinase inhibitor (SU11248). Changes in tumor vascularity were assessed by DCE-MRI and vessel size imaging.