Dynamic Contrast Enhanced Scanning with a Micro-CT Scanner to Study the Effects of Anti-vascular Treatment on Tumor Perfusion in a Mouse Xenograft Model

Category: Molecular and Functional Imaging in Cancer

Ting-Yim Lee¹, Brian Lim², Sharon van Doodewaard¹, Jennifer Hadway¹, Ivan Yeung³, Sarah-Jane Lunt², Richard Hill², Michael Milosevic³, ¹Robarts Research Institute, London, Canada; ²Ontario Cancer Institute, Toronto, Canada; ³Princess Margaret Hospital, Toronto, Canada. Contact e-mail: tlee@imaging.robarts.ca

Source: SMI Conference, 2005

Presentation Number: 597
The purpose of our study is to determine whether changes in tumor perfusion following antivascular treatment can be measured using contrast enhanced dynamic scanning with a micro-CT scanner capable of fast rotation speed(Explore Locus, General Electric Healthcare). Tumor cells from a human fibrosarcoma line were injected into a hind limb of four syngeneic C3H mice. At 2 weeks post, tumor perfusion (BF), blood volume (BV) and vascular mean transit time (MTT) (a marker for interstitial pressure) were measured before and at 1 hour after intratumoral injection of an antivascular drug that targets the tubulin cytoskeleton in endothelial cells. For these measurements, 0.2 ml of contrast (150 mgI/ml) was injected via a tail vein over 15 s and the tumor was scanned at 1 s intervals for 40 s. The other scanning parameters were 80 kVp, 60 mA, 150 micron resolution and 0.9 mm slice thickness. The scanner has a 4 cm axial FOV enabling the tumor and the heart to be imaged together. The arterial input function was obtained from a region of interest placed in the left ventricle. CT Perfusion software (General Electric Healthcare) was then used to measure BF, BV and MTT in the tumor as well as contralateral muscle (CM). BF and BV in tumor and CM decreased after antivascular treatment (P < 0.05) and the respective mean decreases in tumor 30 ± 11% and 43 ± 18% were different from those in CM 9 ± 14 % and 13 ± 13% (P < 0.05). There was a larger mean decrease in MTT ( interstitial pressure) in tumor (20 ± 13%) than in CM (2 ± 26%), however, the difference was not significant. These results suggest that contrast-enhanced dynamic CT scanning holds promise for the monitoring of antivascular and by inference antiangiogenesis treatment of tumors in rodents.

Dynamic High-Resolution Volumetric CT Imaging of Tumours in Mice

Category: Molecular and Functional Imaging in Cancer

Louise Du, Sharon Van Doodewaard, Ting-Yim Lee, David Holdsworth, Robarts Research Institute, London, Canada. Contact e-mail:ldu@imaging.robarts.ca

Source: SMI Conference, 2005

Presentation Number: 115
CT Perfusion has proven to be a powerful clinical tool in detecting and diagnosing cancer in patients by providing quantitative assessment of blood kinematics in tumour angiogenesis. Due to recent advances in molecular biology, there has been an increased interest in the development and imaging of numerous mouse tumour models to study cancer. Current micro-CT systems are capable of spatial resolution as high as 10μm. However, in order to perform dynamic perfusion imaging in mice, quantitative CT image data must be acquired at a rate of at least 1 Hz. Through our collaboration with GE Healthcare, our lab has obtained a novel research prototype pre-clinical CT scanner, the eXplore Locus Ultra, designed specifically for dynamic perfusion imaging in small animals. Using a digital flat-panel detector and a clinical slip-ring gantry, this system is capable of acquiring high-resolution volumetric image data at a rate of 1 Hz, while covering the entire thoracic region of a mouse. The performance of the scanner was demonstrated through the in vivo imaging of 4 C3T mice with KHT tumours. A bolus of 1.5 μl/g of Omnipaque 300 was injected into the tail vein at the beginning of each scan. The arterial input function was obtained from carotid arteries, aorta or pulmonary arteries and tissue time-density curves were deconvolved to generate functional maps of blood flow, blood volume and vascular mean transit time. The values for all three functional maps are increased in the region of the tumour when compared to healthy tissue, thus indicating the presence of increased vasculature in the tumour. The blood flow rate increased from 18.5±2.3 ml/min/100g in the healthy tissue to 32.4±4.1 ml/min/100g in the tumour region, showing a significant difference (p<0.5). Micro-CT has multiple applications in cancer research by providing high-resolution anatomical information and functional information through dynamic perfusion imaging.

Micro-CT Investigation Of Dual-Phase Contrast Enhancement In Liver Tumours

Category: Molecular and Functional Imaging in Cancer

Nancy Ford¹, Kevin Graham², Alan Groom³, Ian MacDonald³, Ann Chambers², Maria Drangova¹, David Holdsworth¹, ¹Robarts Research Institute, London, Canada; ²London Regional Cancer Program, London, Canada; ³University of Western Ontario, London, Canada. Contact e-mail: nford@imaging.robarts.ca

Source: SMI Conference, 2005

Presentation Number: 370
Micro-computed tomography is an important method of imaging rodents non-invasively to achieve high-resolution, volumetric datasets with short acquisition times. Due to the poor soft-tissue contrast inherent to micro-CT imaging, injectable contrast agents have been introduced to increase the contrast between vasculature and background tissue. Our hypothesis was that by knowing the time-course of contrast enhancement, enhanced images of the vasculature and liver could be obtained with a single injection of contrast material. To study contrast enhancement as a function of time, iodinated blood-pool contrast agent (Fenestra VC) was injected, via a tail vein, into immune deficient NIHIII mice. Imaging was performed using a GE Locus Ultra micro-CT scanner to acquire volume datasets in 8 seconds. Each image was reconstructed with an isotropic voxel spacing of 0.15 mm; the entrance dose to the animal was estimated to be 0.07 Gy. Images were acquired prior to and at 0, 0.5, 1, 2, 4, and 6 hours post contrast injection. From this study, we determined that peak enhancement of the vasculature occurs immediately following contrast injection and peak liver enhancement about 6 hours later. This dual-phase imaging protocol was subsequently applied to NIHIII mice injected with HT-29 (human colon carcinoma) cells into the mesenteric vein to target tumor growth to the liver. Respiratory-gated images of free-breathing tumour-bearing mice were acquired using a GE explore RS micro-CT scanner immediately post injection and 6 hours later. The respiratory-gated acquisitions took approximately 25 minutes, with an estimated entrance dose of 0.24 Gy. In this group of mice, the vasculature was well visualized in the images acquired immediately post injection. After 6 hours, the normal liver parenchyma was enhanced, enabling delineation of the tumours, which remained at the baseline value. Dual-phase contrast-enhanced micro-CT can be used to study liver tumours and associated vasculature in mice.

Lee TY, Purdie TG, Stewart E.

Imaging Program, Lawson Health Research Institute, London, Ontario, Canada. e-mail: tell@imaging.robarts.ca

Abstract:
Tumor angiogenesis has significant implications in the diagnosis and treatment of various solid tumors. With the advent of fast, multi-slice CT scanners, CT imaging techniques capable of qualitative and quantitative analysis of tumor angiogenesis have been the subject of extensive investigation in the past 2 decades. The fundamental bases for CT imaging of angiogenesis are both the transport by blood flow of intravenously administered iodinated contrast material to tissue and the exchange by diffusion of these contrast molecules between the intravascular space and the extravascular interstitial space. With current fast CT scanners both tissue and vascular enhancement can be measured and traced over time at small time intervals to allow detailed modeling of the distribution of contrast agent in tissue. Both compartmental and distributed parameter models for contrast transport and exchange have been developed to quantify from the CT data the following angiogenesis related parameters: tissue blood flow, blood volume, mean transit time, contrast arrival time, capillary permeability surface area product and hepatic arterial fraction in case of the liver. This review addresses the following aspects of CT imaging of angiogenesis: 1) basic concepts related to the understanding of both compartmental and distributed parameter models; 2) comparison between both types of models; 3) practical issues with respect to the measurement of the arterial input function, which is required for the solution of both types of models; and, 4) illustration of the application of a distributed parameter model, the Johnson and Wilson model, in a number of experimental studies.

• http://www.minervamedica.it/index2.t?show=R39Y2003N03A0171

Quantification of angiogenesis by functional computed tomography in a Matrigel model in rats

S Phongkitkarun, S Kobayashi, Z Kan, TY Lee, and C Charnsangavej
Acad Radiol 2004; 11: 573.

• Medline

Retrospective Respiratory-Gated Volume Micro-CT of Rodents in Under One Minute

Category: Multimodal Imaging - Instrumentation

Nancy Ford, Andrew Wheatley, David Holdsworth, Maria Drangova, Robarts Research Institute, London, Canada. Contact e-mail: nford@imaging.robarts.ca

Source: SMI Conference, 2005

Presentation Number: 182
Micro-CT has the potential to non-invasively study organ structure in rodents with high resolution and fast image acquisition. Technological advances in micro-CT scanners, including the introduction of dynamic, flat-panel scanners, allows the acquisition of volume images in under 8 seconds. However, motion artefacts associated with the normal respiratory motion of the animal may arise when imaging the abdomen or chest cavity due to the high respiratory rates of rodents. To reduce these artefacts and the accompanying loss of spatial resolution, we propose a respiratory gating technique for volume micro-CT imaging of anaesthetized, free-breathing rodents. A custom-made bed with an embedded pressure chamber was connected to a pressure transducer. Anaesthetized animals were placed in a prone position on the bed with their abdomens located over the chamber. Inhalation motion caused an increase in the chamber pressure, which was converted into a voltage signal by the transducer. Images of the thorax were acquired using a GE Locus Ultra volume micro-CT scanner at 80 kVp, 50 mA and reconstructed with an isotropic voxel spacing of 0.15 mm. During the imaging protocol, the x-ray signal was monitored and recorded, along with the respiratory pressure waveform. Projection images were acquired with up to 10 rotations in less than 1 minute. Respiratory gating was performed retrospectively by reconstructing only the projections that were obtained during the same portion of the respiratory cycle. Gated images in mice and rats exhibit improved definition of the diaphragm boundary and increased conspicuity of the airways and other small structures within the lungs. From these results, we are confident that retrospectively gated volume micro-CT will be a useful tool for imaging the lungs of rodents, as it would be possible to produce images at different respiratory phases enabling dynamic depictions of lung function.