The AAPM/RSNA physics tutorial for residents: search for isotropic resolution in CT from conventional through multiple-row detector

M Mahesh
RadioGraphics 2002; 22: 949.

Abstract:
Computed tomography (CT) is a method of acquiring and reconstructing the image of a thin cross section on the basis of measurements of attenuation. In comparison with conventional radiographs, CT images are free of superimposing tissues and are capable of much higher contrast due to elimination of scatter. Most of the developments in CT since its introduction can be considered as attempts to provide faster acquisition times, better spatial resolution, and shorter computer reconstruction times. From the early designs, the technology progressed with faster scanning times and higher scanning plane resolution, but true three-dimensional (3D) imaging became practical only with helical scanning capabilities. The recent advent of multiple-row detector helical scanners has the capability to produce 3D images that approach the ideal of a true "3D radiograph." Current multiple-row detector scanners can scan 40-cm volume lengths in less than 30 seconds with near-isotropic resolution and image quality that could not be envisioned at the time of Hounsfield’s invention.

• http://radiographics.rsnajnls.org/cgi/reprint/22/4/949

Micro CT Cancer research (Oak Ridge National Lab MicroCT)

Paulus MJ, Gleason SS, Kennel SJ, Hunsicker PR, Johnson DK.
Oak Ridge National Laboratory, TN 37831-6006, USA.

Abstract:
Dedicated high-resolution small animal imaging systems have recently emerged as important new tools for cancer research. These new imaging systems permit researchers to noninvasively screen animals for mutations or pathologies and to monitor disease progression and response to therapy. One imaging modality, X-ray microcomputed tomography (microCT) shows promise as a cost-effective means for detecting and characterizing soft-tissue structures, skeletal abnormalities, and tumors in live animals. MicroCT systems provide high-resolution images (typically 50 microns or less), rapid data acquisition (typically 5 to 30 minutes), excellent sensitivity to skeletal tissue and good sensitivity to soft tissue, particularly when contrast-enhancing media are employed. The development of microCT technology for small animal imaging is reviewed, and key considerations for designing small animal microCT imaging protocols are summarized. Recent studies on mouse prostate, lung and bone tumor models are overviewed

• http://www.imtekinc.com/Neoplasia_reprint.pdf
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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

A Comprehensive Analysis of Subchondral Bone Effects in the MIA Model of Osteoarthritis in the Rat

Category: Molecular Imaging in the Drug Discovery Process
Michael Westmore¹, Kellie Brune¹, Srinivasan Chandrasekhar², Todd Christopher¹, Peter Mitchell², Jennifer Oskins², Jeffrey Wolos¹, Mark Chambers², ¹Eli Lilly & Company, Greenfield, USA; ²Eli Lilly & Company, Indianapolis, USA. Contact e-mail: mwestmor@lilly.com

Source: SMI Conference 2005

Presentation Number: 576
Osteoarthritis is a degenerative joint disease characterized by destruction of articular cartilage, subchondral bone erosion, and associated joint pain. The mono-iodoacetate (MIA) model promotes loss of articular cartilage similar to that seen in humans. In this study, 1 mg of MIA in 50 μl of saline was injected into the left knee joint of 8-week-old male Lewis rats (n=6) while 50 μl of saline was injected into the right knee as a contralateral control. A control group (n=6) had saline injected in both knees. Both knees were imaged by micro-computed tomography (μCT, 47 μm isotropic voxels) at baseline, and at 1, 2, 3, and 4 weeks post injection. The entire subchondral bone region of the tibia was segmented for structural analysis. A comprehensive analysis including bone-mineral density (BMD), structure model index (SMI), anisotropy, connectivity by Euler number calculation, structural parameters from the plate model, and a topological analysis was performed. Highly significant changes in all parameters were observed due to MIA injection relative both to the contralateral control and to the control group as early as 1 week post injection. This model combined with high-resolution μCT has the potential to provide a facile method for the in-vivo screening of potential OA disease-modifying drugs that act through mechanisms influencing subchondral bone turnover.

Using cartilage to repair bone: an alternative approach in tissue engineering

Montufar-Solis D, Nguyen HC, Nguyen HD, Horn WN, Cody DD, Duke PJ.
Dental Branch, Department of Orthodontics, The University of Texas Health Science Center, Houston, TX 77225, USA.

• MedLine

Development of a New Zealand white rabbit model of spinal pseudarthrosis repair and evaluation of the potential role of OP-1 to overcome pseudarthrosis

Grauer JN, Vaccaro AR, Kato M, Kwon BK, Beiner JM, Patel TC, Hilibrand AS, Chiba K, Albert TJ.

• Spine

Impaired Calcification Around Matrix Vesicles of Growth Plate and Bone in Alkaline Phosphatase-Deficient Mice

H. Clarke Anderson*, Joseph B. Sipe*, Lovisa Hessle , Rama Dhamyamraju*, Elisa Atti , Nancy P. Camacho and José Luis Millán

From the Department of Pathology and Laboratory Medicine,* University of Kansas Medical Center, Kansas City, Kansas; The Burnham Institute, La Jolla, California; and the Hospital for Special Surgery, New York, New York

Abstract:
The presence of skeletal hypomineralization was confirmed in mice lacking the gene for bone alkaline phosphatase, ie, the tissue-non-specific isozyme of alkaline phosphatase (TNAP). In this study, a detailed characterization of the ultrastructural localization, the relative amount and ultrastructural morphology of bone mineral was carried out in tibial growth plates and in subjacent metaphyseal bone of 10-day-old TNAP knockout mice. Alizarin red staining, microcomputerized tomography (micro CT), and FTIR imaging spectroscopy (FT-IRIS) confirmed a significant overall decrease of mineral density in the cartilage and bone matrix of TNAP-deficient mice. Transmission electron microscopy (TEM) showed diminished mineral in growth plate cartilage and in newly formed bone matrix. High resolution TEM indicated that mineral crystals were initiated, as is normal, within matrix vesicles (MVs) of the growth plate and bone of TNAP-deficient mice. However, mineral crystal proliferation and growth was inhibited in the matrix surrounding MVs, as is the case in the hereditary human disease hypophosphatasia. These data suggest that hypomineralization in TNAP-deficient mice results primarily from an inability of initial mineral crystals within MVs to self-nucleate and to proliferate beyond the protective confines of the MV membrane. This failure of the second stage of mineral formation may be caused by an excess of the mineral inhibitor pyrophosphate (PPi) in the extracellular fluid around MVs. In normal circumstances, PPi is hydrolyzed by the TNAP of MVs’ outer membrane yielding monophosphate ions (Pi) for incorporation into bone mineral. Thus, with TNAP deficiency a buildup of mineral-inhibiting PPi would be expected at the perimeter of MVs.

• http://ajp.amjpathol.org/cgi/reprint/164/3/841

Bone Formation in Transplants of Human Bone Marrow Stromal Cells and Hydroxyapatite-Tricalcium Phosphate: Prediction with Quantitative CT in Mice

M. H. Mankani, S. A. Kuznetsov, N. A. Avila, A. Kingman, and P. G. Robey
Radiology 2004; 230: 369.

Abstract:

PURPOSE: To determine whether quantitative computed tomography (CT) can be used to estimate the extent of new bone formation in hydroxyapatite–tricalcium phosphate (HA-TCP)–based transplants.

MATERIALS AND METHODS: Bone-forming transplants were generated by attaching cultured human bone marrow stromal cells to aliquots of HA-TCP particles and were placed in subcutaneous pockets in immunocompromised mice. After 8 weeks, the transplants were individually imaged; each scan included a phantom. Overall bone mineral density (BMD) of each transplant was obtained. Hematoxylin-eosin–stained sections of the same transplants were then examined histologically, which is the reference standard for assessing bone formation. The extent of bone in each transplant was scored on a semiquantitative scale ranging from 0 to 4 by three independent blinded observers; the bone score for each transplant was calculated by averaging the three observer scores. BMD was compared with the histologically determined bone score for each transplant. Statistical evaluations included (a) calculation of empiric receiver operating characteristic curves to determine optimum BMD thresholds and (b) determination of the relationship between BMD and bone score, including derivation of Pearson correlation coefficients.

RESULTS: One hundred twenty transplants were evaluated. Average BMD of 600 mg/cm3 K2HPO4 or more was noted in transplants with appreciable bone formation (bone score 3), while average BMD of less than 600 mg/cm3 K2HPO4 was seen in transplants with poor bone formation (bone score < 3) (P < .001). Among transplants with appreciable bone formation, the BMD was proportional to the extent of mineralized matrix present in the new bone.

CONCLUSION: Use of quantitative CT offers a practical approach for the noninvasive determination of new bone formation in mineralizing bone marrow stromal cells and HA-TCP transplants.

• http://radiology.rsnajnls.org/cgi/content/full/230/2/369
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Lung Morphology Measured With Respiratory-Gated Micro-CT Of Free-Breathing Mice

Category: Imaging of Protease Activity in Disease
Nancy Ford¹, Tyler Shaule¹, Erica Martin², James Lewis², Ruud Veldhuizen², David Holdsworth¹, Maria Drangova1, ¹Robarts Research Institute, London, Canada; ²Lawson Health Research Institute, London, Canada. Contact e-mail: nford@imaging.robarts.ca

Source: SMI Conference 2005

Presentation Number: 269
Small animal models of respiratory disease have been used to examine the changes in morphology between normal and diseased animals. In particular, tissue inhibitor metalloproteinase-3 (TIMP-3) deficient mice exhibit enlarged alveolar spaces compared to wild type controls. In this study, we propose a method of measuring lung morphology of free-breathing mice using respiratory-gated micro-CT.
Wild type and TIMP-3-deficient C57/BL6 mice were anaesthetized with a mixture of ketamine and xylazine. For imaging, the free-breathing animals were positioned on a pressure chamber that monitored their respiration externally, using the change in pressure exerted on the chamber caused by the motion of the diaphragm. Respiratory-gated micro-CT images were acquired for each animal at peak inspiration and at end expiration. Images were acquired at 80 kVp, 0.4 mA, with an entrance dose of 0.24 Gy and a scan time of 25-30 minutes, and were reconstructed with an isotropic voxel spacing of 0.087 mm.
For each image, a region of interest containing the lungs was defined and minimum intensity projections through the ROI were generated. Diameter measurements of the trachea and bronchi were recorded, along with the length from the apex to the inferior aspect of the lower lobe of the right lung. An intensity-based seeded region-growing algorithm was used to extract the entire lung and the airways separately and calculate the respective volumes. The average lung density, calculated in Houndsfield units, was -432.87±5.09 HU for the wild type and -472.38±14.42 HU for the TIMP-3 deficient mice (p < 0.05). The functional residual capacity and the tidal volume were also computed for both groups.
Respiratory-gated micro-CT images of free-breathing mice had sufficient resolution and image quality to quantify differences in the mean lung density between wild type and TIMP-3 deficient mice and promises to become a valuable tool for studying lung disease in mouse models.

Murine Lung Tumor Measurement Using Respiratory-Gated Micro-Computed Tomography

Investigative Radiology. 40(5):263-269, May 2005.
Cody, Dianna D. PhD *; Nelson, Christopher L. MS +; Bradley, W Michael BS +; Wislez, Marie MD ++; Juroske, Denise BS ++; Price, Roger E. DVM, PhD *; Zhou, Xian PhD [S]; Bekele, B Nebiyou PhD [S]; Kurie, Jonathan M. MD ++

Abstract:
Objective: The authors explored micro-computed tomography (micro-CT) to quantify lung tumor number and volume in a specific genetic mouse model for lung cancer.

Materials and Methods: The authors used K-rasLA1 mice, which develop lung adenomas and adenocarcinomas through somatic activation of the K-ras oncogene. Tumor number measured using micro-CT and were compared at necropsy (n = 38 mice). Tumor volume measurement precision (n = 39 mice) and accuracy (multiple tumors from a single mouse) were evaluated. Serial lung tumor volume was assessed in a pilot group (n = 8) of mice in vivo.

Results: Tumor number assessed at necropsy and using micro-CT were significantly correlated. Lung tumor volume measurements were both reproducible (2% operator variability) and accurate (6% average error). Strikingly, we observed both tumor growth and shrinkage within individual mice.

Conclusion: Serial measurements provided evidence of tumor heterogeneity, an unexpected finding given the uniformity of the initiating genetic event. Micro-CT may become a powerful tool for murine lung cancer research in vivo.

• Investigative Radiology

Alveolar rhabdomyosarcomas in conditional Pax3:Fkhr mice: cooperativity of Ink4a/ARF and Trp53 loss of function

Charles Keller¹, Benjamin R. Arenkiel², Cheryl M. Coffin³, Nabeel El-Bardeesy⁵, Ronald A. DePinho⁵ and Mario R. Capecchi^4,6
1 Division of Pediatric Hematology-Oncology and Department of Pediatrics, ² Department of Human Genetics, ³ Division of Pediatric Pathology and Department of Pathology, and ⁴ Howard Hughes Medical Institute and Department of Human Genetics, University of Utah, Salt Lake City, Utah 84112, USA; ⁵ Department of Medical Oncology, Dana-Farber Cancer Institute, Department of Medicine, and Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA

Abstract:
Alveolar rhabdomyosarcoma is an aggressive childhood muscle cancer for which outcomes are poor when the disease is advanced. Although well-developed mouse models exist for embryonal and pleomorphic rhabdomyosarcomas, neither a spontaneous nor a transgenic mouse model of alveolar rhabdomyosarcoma has yet been reported. We report the first mouse model of alveolar rhabdomyosarcoma using a conditional Pax3:Fkhr knock-in allele whose activation in late embryogenesis and postnatally is targeted to terminally differentiating Myf6-expressing skeletal muscle. In these mice, alveolar rhabdomyosarcomas occur but at low frequency, and Fkhr haploinsufficiency does not appear to accelerate tumorigenesis. However, Pax3:Fkhr homozygosity with accompanying Ink4a/ARF or Trp53 pathway disruption, by means of conditional Trp53 or Ink4a/ARF loss of function, substantially increases the frequencies of tumor formation. These results of successful tumor generation postnatally from a target pool of differentiating myofibers are in sharp contrast to the birth defects and lack of tumors for mice with prenatal and postnatal satellite cell triggering of Pax3:Fkhr. Furthermore, these murine alveolar rhabdomyosarcomas have an immunohistochemical profile similar to human alveolar rhabdomyosarcoma, suggesting that this conditional mouse model will be relevant to study of the disease and will be useful for preclinical therapeutic testing.

• http://www.genesdev.org/cgi/reprint/18/21/2614

Improved method of in vivo respiratory-gated micro-CT imaging

Erin B Walters, Kunal Panda, James A Bankson, Ellana Brown and Dianna D Cody
Department of Imaging Physics, Unit 56, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA

Abstract:
The presence of motion artifacts is a typical problem in thoracic imaging. However, synchronizing the respiratory cycle with computed tomography (CT) image acquisition can reduce these artifacts. We currently employ a method of in vivo respiratory-gated micro-CT imaging for small laboratory animals (mice). This procedure involves the use of a ventilator that controls the respiratory cycle of the animal and provides a digital output signal that is used to trigger data acquisition. After inspection of the default respiratory trigger timing, we hypothesized that image quality could be improved by moving the data-acquisition window to a portion of the cycle with less respiratory motion. For this reason, we developed a simple delay circuit to adjust the timing of the ventilator signal that initiates micro-CT data acquisition. This delay circuit decreases motion artifacts and substantially improves image quality.

• IoP Electronic Journals

In Vivo Respiratory-Gated Micro-CT Imaging in Small-Animal Oncology Models

Cavanaugh D.¹; Johnson E.¹; Price R.E.¹; Kurie J.¹; Travis E.L.¹; Cody D.D.¹

Source: Molecular Imaging, 1 January 2004, vol. 3, no. 1, pp. 55-62(8)

Abstract:
Micro-computed tomography (micro-CT) is becoming an accepted research tool for the noninvasive examination of laboratory animals such as mice and rats, but to date, in vivo scanning has largely been limited to the evaluation of skeletal tissues. We use a commercially available micro-CT device to perform respiratory gated in vivo acquisitions suitable for thoracic imaging. The instrument is described, along with the scan protocol and animal preparation techniques. Preliminary results confirm that lung tumors as small as 1 mm in diameter are visible in vivo with these methods. Radiation dose was evaluated using several approaches, and was found to be approximately 0.15 Gy for this respiratory-gated micro-CT imaging protocol. The combination of high-resolution CT imaging and respiratory-gated acquisitions appears well-suited to serial in vivo scanning.

• Ingenta Connect

New techniques and developments in physiologic imaging of airways

RH Brown and E Zerhouni
Radiol Clin North Am 1998; 36: 211.

Abstract: Recently, noninvasive imaging methods for assessing regional and individual airway responsiveness have been developed in animal models and applied to humans with obstructive lung disease. This article examines the technique of high-resolution CT scan and MR imaging and their applications to the imaging of airways.

• Medline

Evaluation of in vivo total and regional air content and distribution in primate lungs with high-resolution CT

BF Mullan, JR Galvin, J Zabner, and EA Hoffmann
Acad Radiol 1997; 4: 674.

Abstract:

RATIONALE AND OBJECTIVES: The authors sought to determine whether gray-scale quantitative information from high-resolution computed tomography (CT) could reliably yield estimates of lung air content and help determine changes in air content with lung inflation and deflation. MATERIALS AND METHODS: High-resolution CT images (n = 40) of lungs of two anesthetized monkeys were obtained after inflation with known air volumes. Percentage air content was calculated for each voxel, and lung volumes and patterns of air distribution were determined. RESULTS: When corrected for pressure and temperature, high-resolution CT-based volumes correlated closely with inflation volumes (r = .99; standard error = 3.4%). Patterns of regional change in air content demonstrated known patterns of ventilation.

CONCLUSION: Although the high-spatial-frequency algorithm used in high-resolution CT enhances edges of structures and improves visualization of anatomic detail, gray-scale values from the same high-resolution CT data set remain a reliable index of regional lung attenuation.

• Medline

Hyperoxia-induced diffuse alveolar damage in pigs: correlation between thin-section CT and histopathologic findings

K Ichikado, M Suga, Y Gushima, T Johkoh, K Iyonaga, T Yokoyama, O Honda, Y Shigeto, S Tomiguchi, M Takahashi, H Itoh, J Ikezoe, NL Müller, and M Ando
Radiology 2000; 216: 531.

Abstract:

PURPOSE: To determine whether lung abnormalities at thin-section computed tomography (CT) in experimental hyperoxic lung injury correlate with the pathologic phases of diffuse alveolar damage (DAD).

MATERIALS AND METHODS: Eighteen juvenile pigs were exposed to more than 80% oxygen—for 24, 48, 72, 96, or 120 hours—or room air in sealed cages. Their removed lungs were inflated with air infused through the trachea and examined with thin-section CT. Two independent observers, without knowledge of the exposure times, compared 63 areas selected on the CT scans with the corresponding pathologic and histologic findings, which were evaluated independently by two pathologists.

RESULTS: CT findings correlated well with histologic findings ( = 0.86, P < .001), which corresponded to the pathologic phases of DAD. All areas of normal CT attenuation, eight of nine spared regions within areas of opacity, and two of 15 areas of ground-glass opacity corresponded to the early exudative pathologic phase of DAD. All areas that showed traction bronchiolectasis at CT corresponded to the early proliferative pathologic phase. There was good observer agreement regarding the interpretation of CT findings ( statistic, >0.60) and histologic results ( 0.70).

CONCLUSION: Thin-section CT findings reflect the pathologic phases of DAD, although the early exudative phase cannot be specifically depicted by thin-section CT. Traction bronchiolectasis on a CT scan suggests progression to the proliferative phase.

• http://radiology.rsnajnls.org/cgi/content/full/216/2/531
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Value of 3D-volume rendering in the assessment of coronary arteries with retrospectively ECG-gated multislice spiral CT.

AH Mahnken, JE Wildberger, AM Sinha, K Dedden, S Stanzel, R Hoffmann, T Schmitz-Rode, and RW Gunther
Acta Radiol 2003; 44: 302.

Abstract:
To assess the diagnostic value and measurement precision of 3D volume rendering technique (3D-VRT) from retrospectively ECG-gated multislice spiral CT (MSCT) data sets for imaging of the coronary arteries. MATERIAL AND METHODS: In 35 patients, retrospectively ECG-gated MSCT of the heart using a four detector row MSCT scanner with a standardized examination protocol was performed as well as quantitative X-ray coronary angiography (QCA). The MSCT data was assessed on segmental basis using 3D-VRT exclusively. The coronary artery diameters were measured at the origin of each main coronary branch and 1 cm, 3 cm and 5 cm distally. The minimum, maximum and mean diameters were determined from MSCT angiography and compared to QCA. RESULTS: A total of 353 of 525 (67.2%) coronary artery segments were assessable by MSCT angiography. The proximal segments were more often assessable when compared to the distal segments. Stenoses were detected with a sensitivity of 82.6% and a specificity of 92.8%. According to the Bland-Altman method the mean differences between QCA and MSCT ranged from -0.55 to 1.07 mm with limits of agreement from -2.2 mm to -2.7 mm.

CONCLUSION: When compared to QCA, the ability of 3D-VRT to quantitatively assess coronary artery diameters and coronary artery stenoses is insufficient for clinical purposes.

• Medline

Techniques for the detection of coronary atherosclerosis: multi–detector row CT coronary angiography

TJ Vogl, ND Abolmaali, T Diebold, K Engelmann, M Ay, S Dogan, G Wimmer-Greinecker, A Moritz, and C Herzog
Radiology 2002; 223: 212.

Abstract:

PURPOSE: To investigate the accuracy of different computed tomographic (CT) reformation techniques in assessing the coronary arteries.

MATERIALS AND METHODS: Sixty-four patients undergoing both multi–detector row CT and invasive coronary angiography were consecutively included in a retrospective study. CT scans were obtained with collimation of 4 x 1 mm, pitch of 1.5, and rotation time of 500 msec. Retrospective electrocardiographic gating was used for image reconstruction, with 1.25-mm section thickness and 0.5-mm increment. The CT data set of each patient was evaluated by independent observers using transverse scanning, virtual endoscopic, and three-dimensional reformation and multiplanar reformation.

RESULTS: Hemodynamically relevant stenoses (>50%) were detected with highest sensitivity at transverse scanning (58 of 79 [73.4%] stenoses), followed by virtual endoscopic (38 of 79 [48.1%] stenoses) and three-dimensional reformation (34 of 79 [43.0%] stenoses), and multiplanar reformation (37 of 79 [46.8%] stenoses). Atherosclerotic plaques were identified with comparable sensitivities at transverse scanning (143 of 218 plaques [65.6%]) and at three-dimensional (139 of 218 [63.8%] plaques) and virtual endoscopic reformation (136 of 218 [62.4%] plaques). Multiplanar reformation had distinctly poorer results (217 of 218 [58.3%] plaques). Combined interpretation with all four techniques increased sensitivity to 74.7% (59 of 79) for stenosis and 71.6% (156 of 218) for atherosclerosis. Calculated overall specificity was 91.4% or greater. Sufficient vascular evaluation was possible only in vessels larger than 1.6 mm in diameter. Thus, even in patients with heart rates below 60 bpm, only 80.0% of all coronary segments could be visualized, while at higher frequencies, visibility decreased to 66.2%.

CONCLUSION: Although multi–detector row CT is a favorable alternative procedure in evaluating coronary arteries, its clinical value still is restricted to low heart rates and proximal coronary arterial segments.

• http://radiology.rsnajnls.org/cgi/reprint/223/1/212

From the RSNA refresher courses: CT angiography: clinical applications in the abdomen

EK Fishman
RadioGraphics 2001; 21: 3S.

Abstract: The development of spiral computed tomography (CT) and subsequently multidetector CT has provided unparalleled opportunities for advancement of CT technology and clinical applications. One of the most influential developments has been CT angiography, which is the use of thin-section CT combined with postprocessing of imaging data by using a variety of three-dimensional reconstruction techniques to produce vascular maps that equal or exceed those provided by classic angiography in many applications. In the evaluation of pancreatic disease, the use of multidetector CT angiography enables the radiologist to produce vascular maps that clearly show tumor invasion of vasculature and the relationship of vessels to pancreatic masses. Anatomic areas for which the three-dimensional display is especially helpful include the confluence of the portal vein and the superior mesenteric vein and the more distal portions of the portal vein. Preliminary studies indicate that CT angiography may prove beneficial in the evaluation of ischemic bowel and active Crohn disease. CT angiography has proved extremely valuable for applications such as preoperative planning for hepatic resection, preoperative evaluation and planning for liver transplantation, pretreatment planning for patients considered for hepatic arterial infusion chemotherapy, and pretreatment evaluation of portal vein patency for a variety of reasons. CT angiography can also provide supplemental information in patients with cirrhosis, upper gastrointestinal tract bleeding due to varices, or primary extrahepatic neoplasms.

• Medline

Acute Myocardial Infarction: Contrast-enhanced Multi-Detector Row CT in a Porcine Model

U. Hoffmann, R. Millea, C. Enzweiler, M. Ferencik, S. Gulick, J. Titus, S. Achenbach, D. Kwait, D. Sosnovik, and T. J. Brady
Radiology 2004; 231: 697.

Abstract:

PURPOSE: To assess the role of contrast material–enhanced retrospectively electrocardiographically (ECG) gated multi–detector row computed tomography (CT) in the detection of acute myocardial infarction in a porcine model of total coronary occlusion.

MATERIALS AND METHODS: Seven Yorkshire farm pigs were studied with contrast-enhanced retrospectively ECG-gated multi–detector row CT 3 hours after total occlusion of the distal left anterior descending artery (n = 5) or the second diagonal branch (n = 2). Reformatted short-axis end-systolic and end-diastolic CT data sets were assessed for myocardial perfusion deficits, coronary occlusion, and abnormal myocardial wall motion. Perfusion deficits were compared with microsphere-determined blood flow and triphenyltetrazolium chloride (TTC)–stained tissue samples for infarct assessment by using Bland-Altman analysis and analysis of variance.

RESULTS: Myocardial perfusion deficits, occlusion of the left anterior descending artery or second diagonal branch, and akinesis of the infarcted segment were identified in all five animals that completed the study. One animal died, and one data set had nondiagnostic image quality. The CT end-diastolic (mean, 16.1% ± 4.8 [SD]; range, 8.6%–22.2%) and end-systolic (mean, 17.0% ± 6.4; range, 8.7%–26.8%) volume of perfusion deficit was similar to that of infarcted tissue at TTC staining (mean, 13.6% ± 6.0; range, 7.8%–30.9%). Infarcted myocardium at CT demonstrated a 76.1% reduction in microsphere-determined blood flow and a significant reduction of myocardial CT attenuation compared with normal myocardium (P < .01). Myocardial wall motion analysis demonstrated absence of systolic wall thickening in infarcted myocardium.

CONCLUSION: Multi–detector row CT with retrospective ECG gating permits the detection and further characterization of acute myocardial infarction in a porcine model of complete coronary occlusion.

• http://radiology.rsnajnls.org/cgi/reprint/231/3/697

Multiphasic injection method for uniform prolonged vascular enhancement at CT angiography: pharmacokinetic analysis and experimental porcine model

KT Bae, HQ Tran, and JP Heiken
Radiology 2000; 216: 872.

Abstract:

PURPOSE: To determine if multiphasic injection provides uniform, prolonged vascular contrast medium enhancement at computed tomographic (CT) angiography.

MATERIALS AND METHODS: With a computer-based, compartmental model of the cardiovascular system, theoretic analysis was performed to estimate an injection algorithm for uniform, prolonged vascular enhancement. For algorithm validation, four pigs were scanned after intravenous injection of 50 or 70 mL of contrast medium (282 mg of iodine per milliliter). Uni-, bi-, and multiphasic injection schemes were tested. In most cases, the initial injection rate was 2 mL/sec. In each CT study, 27 dynamic images were acquired every 2 seconds at a fixed mid–abdominal aortic level. Time-enhancement curves were calculated. Injection duration, peak aortic enhancement, and enhancement uniformity (duration of enhancement achieved within 90% of the peak [90% DCE]) were evaluated.

RESULTS: Theoretic and experimental results agreed well. Compared with uniphasic injection, biphasic injection resulted in more prolonged enhancement but generated two enhancement peaks with a valley between, and multiphasic injection yielded more uniform and prolonged enhancement. With 50- and 70-mL multiphasic injections, respectively, injection duration increased by 32% and 51%, peak enhancement decreased by 19% and 18%, and 90% DCE increased by 81% and 94%.

CONCLUSION: Uniform, prolonged vascular enhancement, which is desirable for CT angiography and essential for steady-state quantification of blood volume in organs, can be achieved with multiphasic injection.

• http://radiology.rsnajnls.org/cgi/content/full/216/3/872

Contrast medium–induced pulmonary edema is aggravated by silicone contamination in rats

T Sendo, M Hirakawa, K Fujie, Y Kataoka, and R Oishi
Radiology 1999; 212: 97.

Abstract:

PURPOSE: To examine the effect of silicone contamination, which occurs in clinical settings during vial preparation with disposable syringes, on contrast medium–induced pulmonary edema in rats.

MATERIALS AND METHODS: Ioxaglate, ioversol, and iohexol, silicone-containing physiologic saline solutions, and three silicone-containing contrast media were separately, intravenously injected at 1.5 mL/min in rats. Pulmonary edema was evaluated as changes in the relative lung weight and in the water, sodium, and potassium contents of the lung.

RESULTS: Intravenous injection of ioxaglate induced marked pulmonary edema, even with a dose of only 4 g of iodine per kilogram of body weight. In contrast, ioversol and iohexol induced significant pulmonary edema only after the injection of large doses (6 g of iodine per kilogram; P < .05). The injection of 4 µL/mL silicone-containing physiologic saline at a dose of 18.75 mL/kg also produced marked pulmonary edema, whereas doses of 6.25 and 12.5 mL/kg showed no significant influence. The addition of an ineffective dose (12.5 mL of physiologic saline per kilogram of body weight) of silicone in contrast medium substantially aggravated the pulmonary edema induced by the contrast medium alone; this phenomenon was also confirmed with morphologic observation.

CONCLUSION: Ionic contrast media are more toxic to the endothelial cells than are nonionic contrast media. Silicone contamination might be one of the causes of pulmonary edema after intravenous injection. However, caution must be exercised in extrapolating these results to humans.

• http://radiology.rsnajnls.org/cgi/content/full/212/1/97
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Angiopoietin-1 Causes Reversible Degradation of the Portal Microcirculation in Mice Implications for Treatment of Liver Disease

Nicole L. Ward*, Alexandra L. Haninec* , Paul Van Slyke* , John G. Sled , Celina Sturk* , R. Mark Henkelman , Ian R. Wanless|| and Daniel J. Dumont* **

Abstract:
In many different liver diseases, such as cirrhosis, degradation of the microcirculation, including obliteration of small portal or hepatic veins contributes to disease-associated portal hypertension. The present study demonstrates the importance of angiogenesis in the establishment of arteriovenous shunts and the accompanying changes to the venous bed. One aspect of angiogenesis involves the branching of new vessels from pre-existing ones, and the molecular mechanisms controlling it are complex and involve a coordinated effort between specific endothelial growth factors and their receptors, including the angiopoietins. We modulated the hepatic vasculature in mice by conditionally expressing angiopoietin-1 in hepatocytes. In mice exposed to angiopoietin-1 during development, arterial sprouting, enlarged arteries, marked loss of portal vein radicles, hepatic vein dilation, and suggestion of arteriovenous shunting were observed. Most importantly, these phenotypic changeswere completely reversed within 14 days of turning off transgene expression. Expression of excess angiopoietin-1 beginning in adulthood did not fully recapitulate the phenotype, but did result in enlarged vessels. Our findings suggest that controlling excessive angiogenesis during liver disease may promote the restoration of the portal vein circuit and aid in the resolution of disease-associated portal hypertension.

• http://ajp.amjpathol.org/cgi/content/full/165/3/889

Early changes in liver perfusion caused by occult metastases in rats: detection with quantitative CT

CA Cuenod, I Leconte, N Siauve, A Resten, C Dromain, B Poulet, F Frouin, O Clément, and G Frija
Radiology 2001; 218: 556.

Abstract:

PURPOSE: To determine whether computed tomography (CT) can depict liver hemodynamic changes caused by occult hepatic micrometastases in rat.

MATERIALS AND METHODS: Liver micrometastases (mean diameter, 500 µm ± 300) were produced in seven BD IX rats by injecting 107 DHDK12 PROb colorectal carcinoma cells into the spleen. Macrometastases (mean diameter, 7 mm ± 3) were produced in four other rats. Five normal rats were studied as controls. CT images were obtained every 300 msec for 30 seconds during the injection of 1 mL per kilogram of body weight of contrast medium. The time-attenuation curves of the aorta, portal vein, and liver were used to calculate liver perfusion with a deconvolution model designed for the dual blood supply.

RESULTS: Micrometastases in an apparently normal liver caused a 34% decrease in portal blood flow and a 25% increase in the mean transit time for the blood to pass through the liver. These findings suggest increased resistance in the sinusoidal capillaries. Similar but greater changes were found in the macrometastases.

CONCLUSION: Occult liver micrometastases in rats generate changes in liver perfusion that can be detected with CT.

• http://radiology.rsnajnls.org/cgi/content/full/218/2/556
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A Novel Method for Endotracheal Intubation of Mice and Rats Used in Imaging Studies

Belinda Rivera, Shonna Miller, Ellana Brown, Riger Price
Department of Imaging Physics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.

• PubMed

Ultrasound-guided left-ventricular catheterization: a novel method of whole mouse perfusion for microimaging

Zhou YQ, Davidson L, Henkelman RM, Nieman BJ, Foster FS, Yu LX, Chen XJ.
Mouse Imaging Centre, Department of Integrative Biology, The Hospital for Sick Children, Toronto, Canada.

Abstract: We describe a novel technique to perform whole-body perfusion fixation in mice with specific relevance to micro-imaging. With the guidance of high-frequency ultrasound imaging, we were able to perfuse fixative and contrast agents via a catheter inserted into the left ventricle, and therefore preserved the integrity of the chest and abdominal cavity. In this preliminary study, our success rate over 15 animals was 73%. We demonstrate applications of this technique for magnetic resonance imaging and micro-CT, but we expect that this method can be generally applied to whole-body perfusions of other small animals in which the intact body is necessary.

• http://www.nature.com/labinvest/journal/v84/n3/pdf/3700038a.pdf
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Mouse Phenotyping using µCT: an example

Category: Multimodal Imaging - Instrumentation

Philippe Choquet¹, Alexandre Calon², Elodie Breton¹, Christian Goetz¹, Claire Domon², Jean-Noë^l Freund², André Constantinesco¹, ¹Service de biophysique et médecine nucléaire, HUS, CHU Hautepierre, Strasbourg, France; ²INSERM U682, Strasbourg, France. Contact e-mail: philippe.choquet@chru-strasbourg.fr

Source: SMI Conference, 2005

Presentation Number: 188
Anatomical variable phenotype in mutant mice could be assessed ex vivo. By adequate use of µCT, we are able to analyze non-invasively abnormalities in living subjects. The Cdx2 heterozygote mutants, the model chosen, exhibit skeletal abnormalities as well as early development of intestinal polyps (1). Material and Methods
We use a µCT eXplore LOCUS (GE Healthcare, London, Canada). Two iodinated contrast agents with different dilutions are administered in Cdx2 mice under anesthesia : IOMERON 400 (Bracco, Milan, Italy) by intraperitoneal injection and TELEBRIX (Guerbet, Roissy, France), via intrarectal route. Results
Squelettal abnormalities are easily documented due to the advantage of X-rays for bone studies (Figure 1). For intestinal polyps, the use of a double contrast allow for perfect delination of tumor in caecum (Figure 2). The intestinal wall is clearly seen and its thickness could be measured. Conclusion
The lack of natural contrast in µCT could be transcend by appropriate use of contrast agents. Administration routes guarantee non invasiveness and consequently open the door to longitudinal studies. It gives 3D isotropic volumes: in this study, spatial resolution is limited to (93)3 µm3 to avoid radiation penalties.
1. Chawengsaksophak K, James R, Hammond VE, Kontgen F, Beck F. Homeosis and intestinal tumours in Cdx2 mutant mice. Nature. 1997 Mar 6;386(6620):84-7.

Practical Vessel Imaging by Computed Tomography in Live Transgenic Mouse Models for Human Tumors

Category: Molecular and Cellular Mechanisms of Angiogenesis

Authors: Patrick Hawkes¹, Gordon Kindlmann², David Weinstein², Greg Jones², Charles Keller³, 1University of Utah, Department of Bioengineering, Salt Lake City, USA; ²University of Utah, Scientific Computing and Imaging Institute, Salt Lake City, USA; ³The University of Texas Health Science Center, Children's Cancer Research Institute, San Antonio, USA. Contact e-mail: pjhawkes@yahoo.com

Source: SMI Conference 2005

Presentation Number: 297 Evaluating the preclinical therapeutic responses of transgenic mice forming tumors in situ is a complex task because tumor onset is variable and tumor site may vary, often juxtaposed to bone. Contrast-enhanced small animal computed tomography is a promising economical and highly quantitative tool for serially assessing tumor vasculature in living mice; however, practical guidelines remain to be established. Using a long-acting iodinated triglyceride blood pool contrast agent, we developed optimized scanner acquisition parameters and volume rendering techniques for examining the intermediate and large vessels of tumors in transgenic mice. We found that multiple-frame, 360-720 view acquisitions were mandatory for clarifying bone and soft tissue from vessel contrast. This finding was consistent in volume renderings using a 1-dimensional transfer function where voxel color and opacity were assigned in proportion to density, and a 2-dimensional transfer function where voxel color and opacity were assigned in proportion to density and gradient magnitude. This study lays groundwork for the qualitative and quantitative assessment of anti-angiogenesis therapies in preclinical studies using transgenic mice.