|Assessing Tumor Perfusion & Permeability Using MRI|
Monitoring Non Invasively by Contrast Enhanced MRI
the Decrease in Tumors Interstitial Fluid Pressure Following Collagenase
Yaron Hassid1, raanan margalit1, Erez Eyal1, Edna Furman-Haran1, Hadassa Degani1
1Weizmann Institute of Science, Rehovot, Israel
Many solid tumors show an increased interstitial fluid pressure (IFP), which forms a physical barrier to drug delivery. We developed a model-based analysis of slow infusion CE-MRI, which integrates GdDTPA pharmacokinetics during slow i.v. infusion and its distribution at steady state. This method was applied to test the efficacy of collagenase in modulating IFP in human H460 non-small-cell lung carcinoma xenografts that exhibited high IFP. Sequential CE-MRI monitoring studies have shown that collagenase significantly reduced tumor IFP within 5 h after its administration. This was further confirmed by the 'wick in needle' technique.
|The Effect of Tumor Proteases on Invasion and
Eva Christina Woenne1, 2, Stefan Zwick1, 2, Ralph Strecker3, Arne Hengerer2, Matthias Taupitz4, Joerg Schnorr4, 5, Margareta M. Mueller1, Wolfhard Semmler1, Fabian Kiessling1
1German Cancer Research Center, Heidelberg, Germany; 2Siemens Medical Solutions, Erlangen, Germany; 3Siemens Medical Solutions, Erlangen , Germany; 4Charité, Berlin, Germany; 5Ferropharm, Teltow, Germany
Vessel Size Imaging (VSI) can be used to determine the mean vessel diameter in tumors. In this study the effect of Matrix-Metallo-Proteinases inhibition (MMPI) on VSI and tumor vascularity (HF-VPDU) was investigated. Upon MMPI vascularity decreased, while mean tumor vessel diameter increased in tumor xenografts of nude mice. Taking into account histological analyzes, the increasing mean tumor vessel diameter can be explained by regression and maturation of small vessel and might be triggered by the change of VEGF und PDGF expression that we observed in vitro upon MMPI.
Combination of DCE and DSC MRI: Added
Value in the Study of Tumor Vascularization
Melanie Heilmann1, 2, Steven Sourbron3, Christine Walczak1, 2, Andreas Biffar3, Julien Vautier1, 2, Michael Peller3, Andreas Volk1, 2
1Institut Curie, Orsay, France; 2INSERM, Orsay, France; 3Ludwig-Maximilian-University Munich, Munich, Germany
Combination of DCE and DSC MRI was realized by simultaneous measurement of T1 and T2* kinetics. In a subcutaneous xenograft model implanted in nude mice examined at 4.7T, a 6 kDa CA was suitable for assessing heterogeneous capillary permeability by measuring Ktrans, whereas a 0.5kDa CA yielded perfusion weighted Ktrans values. Furthermore, a description of R2*(t) in the presence of CA leakage was proposed yielding the parameters κ 20 and κ 21. They are thought to be related to intra-voxel cellular distribution and vascular architecture. Combined DCE-DSC MRI holds potential to improve tumor characterization.
Post-Radiation Change in MRI Dynamic Contrast
Enhanced Ktrans Did Not Explain Tumor Reoxygenation of Irradiated
Naturally-Occurring Canine Tumors
Susan Kraft1, Nadira Trncic2, Ed Ashton3, Susan LaRue1
1Colorado State University, Fort Collins, USA; 2Colorado State University, Fort Collins , USA; 3VirtualScopics Inc, Rochester, New York, USA
Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) was performed on 9 dogs with naturally-occurring tumors before and after a 3 Gy fraction of radiation. In conjunction with DCE-MRI, we measured tumor oxygen levels, microvascular perfusion and density, apoptosis and interstitial fluid pressure to investigate mechanisms involved in reoxygenation. All hypoxic tumors became normoxic after the 3 Gy fraction, with increased mean/median pO2 and decreased hypoxic fraction, whereas mean Ktrans decreased. This Ktrans decrease occurred in the presence of decreased interstitial fluid pressures and increased apoptosis, so improved vascular delivery did not explain the concurrent reoxygenation of tumors.
Novel Insights Into Intravenous Bradykinin
Analogue-Mediated Vasomodulation from Dynamic Contrast-Enhanced MRI of
RG-2 Rodent Malignant Gliomas
Hemant Sarin1, 2, Steve Huntz Fung, 12, Ariel Shaya Kanevsky1, Auh Sungyoung1, John Alexander Butman1
1National Institutes of Health, Bethesda, USA; 2Massachusetts General Hospital, Boston, USA
Intravenous infusion of Cereport, a synthetic bradykinin analogue, has been shown by quantitative autoradiography (QAR) to temporarily enhance drug delivery to malignant gliomas. Although historically QAR has been utilized to measure tumor vascular parameters during systemic vasomodulation, the major limitations of this method include incompleteness of vascular input function (VIF) shape determination due to manual sampling of blood at only certain specific time points, and inability to acquire tumor tissue concentration data over time in the same animal. DCE MRI allows for continuous measurement of change in Gd-DTPA concentration within brain vasculature and glioma tissue over time. In this study we utilized Gd-DTPA DCE MRI to measure changes in tumor vascular parameters within the same RG-2 rat glioma at baseline and during systemic vasomodulation with short-acting and long-acting bradykinin analogues, Met-Lys-bradykinin (Met-Lys-BK) and Cereport, respectively.
Vessel Size Index MRI: Validation with Micro-CT
Sharon E. Ungersma1, Calvin Ho1, Glenn Pacheco1, Jed Ross1, Joan M. Greve1, Franklin V. Peale Jr. 1, Sarajane Ross1, Richard A. D. Carano1
1Genentech, Inc., South San Francisco, California , USA
Vessel size index MRI uses changes in T2 and T2* after introduction of an iron oxide contrast agent to determine the mean vessel size within a voxel. One method by which vessel size measurements of tumors have been done previously is ex vivo micro-CT angiography. Here, we validate the VSI measurement by correlation with micro-CT vessel size measurements of the same tumors. We restrict the VSI analysis to viable tumor tissue as determined with multispectral clustering. This requires no additional scans beyond the VSI measurement and can improve accuracy of MRI parameter measurement by eliminating necrotic regions from the analysis.
DOCENT- Dynamic Oxygen Challenge
Evaluated by NMR T1 and T2* of Tumors
Jesus Pacheco-Torres1, 2, Dawen Zhao1, Angelina Contero1, Peter Peschke3, Ralph Peter Mason1
1The University of Texas Southwestern Medical Center, Dallas, Texas, USA; 2 Instituto de Investigaciones Biomédicas "Alberto Sols" - CSIC, Madrid, Spain; 3DKFZ German Cancer Center, Heidleberg, Germany
Hypoxia influences tumor response to therapy: thus techniques are needed to assess hypoxia and potential modulation. T2*-weighted (BOLD) and T1-weighted (TOLD: Tissue Oxygen Level Dependant) contrast MRI should provide insight into tumor oxygenation. We examined these non-invasive techniques as surrogates for quantitative pO2 measurements for response to carbogen breathing of two tumor sublines (AT1 and HI) noted for their different levels of hypoxia and response to hyperoxic gas breathing. Changes in T1- and T2*-weighted signal intensities corresponded with quantitative 19F NMR oximetry. Since such measurements are entirely non-invasive they offer the potential rapid translation to the clinic.
Investigating the Influence of Physiological
Variation on the Form of the Arterial Input Function in DCE-MRI
Ross A. Little1, Caleb Roberts1, Yvon Watson1, Marietta Scott2, Gio A. Buonaccorsi1, Susan Cheung1, Karen Davies1, James P. O'Connor1, Geoff J. Parker1
1University of Manchester, Manchester, UK; 2AstraZeneca, Macclesfield, Cheshire, UK
This study investigates associations between arterial input functions (AIFs) and readily-available physiological measurements to assess whether change in AIF form between individuals is due to measurement noise and error or if there are detectable underlying physiological influences. Forward stepwise multiple linear regression models were constructed and first pass peak height (FPPH) and the ratio of second pass peak height to FPPH were found to be related to age (r2 = 0.30 and 0.47 respectively). The measured AIF does seem to reflect underlying physiological variation and it may be possible to utilise this to improve the accuracy of population representative AIFs.
|Prediction of Treatment Response in Head and Neck
Cancer Using DCE-MRI
Sungheon Kim1, Laurie A. Loevner1, Larry Dougherty1, Harry Quon1, Eric J. Sherman1, Gregory S. Weinstein1, Harish Poptani1
1University of Pennsylvania, Philadelphia, USA
The purpose of this study was to evaluate the feasibility of using DCE-MRI data with the shutter-speed model (SSM) analysis to predict response to chemo/radiation therapy in the head and neck squamous cell carcinoma (HNSCC). MRI data was acquired from thirty two patients who were newly diagnosed with HNSCC with no prior treatment. Pretreatment transfer constant (Ktrans) and intracellular water exchange time (ti) showed significant difference between the complete responders and partial responders, determined at the end of the treatment. Classification of treatment response based on SSM parameters had a sensitivity of 100% and a specificity of 75%.
DCE-MRI of Human Brain Tumors Using Gadoteridol and
Jeffrey Moses Njus1, Csanad G. Varallyay2, John W. Grinstead3, Xin Li1, Charles S. Springer, Jr. 1, Edward A. Neuwelt2, William D. Rooney1
1Oregon Health and Science University, Portland, Oregon, USA; 2Oregon Health and Science University, Portland, USA; 3Siemens Medical Solutions, Inc, Portland, USAIn regions of high vascular permeability, as is typical in glioblastoma multiforme (GBM), the accurate quantification of blood volume can be difficult or impossible using low molecular weight Gd(III) contrast reagents (CR). This difficulty may be overcome using macromolecular iron oxide CRs such as ferumoxytol, which remain essentially intravascular at short times after administration; even in malignant brain tumors. In this study, we demonstrate a simple, yet novel mapping method using a Gd and an iron-oxide CR serially to quantify cerebral blood volume and BBB permeability in human GBM.