No abstract

Knowledge of normal cerebrovascular volumetric flow rate (VFR) dynamics is of interest for establishing baselines, and for providing input data to cerebrovascular model studies. Retrospectively gated phase contrast magnetic resonance imaging was used to measure time-resolved VFR waveforms from the two internal carotid arteries (ICA) and two vertebral arteries (VA) of 17 young, normal volunteers (16M:1F) at rest in a supine posture. After normalizing each waveform to its respective cycle-averaged VFR, the timing and amplitude of feature points from the individual waveforms were averaged together to produce archetypal ICA and VA waveform shapes. Despite significant inter-individual differences in cycle-averaged VFR within the ICA compared to VA (275+/-52 versus 91+/-18 mL min-1), the respective waveform shapes were qualitatively similar overall. The VA waveform shape did, however, exhibit significantly higher amplitudes (e.g., peak:average VFR of 1.78+/-0.30 versus 1.66+/-0.16; p<0.05) and significantly higher variability both between and within subjects. A significant correlation was observed between peak and cycle-averaged VFR, suggesting that the representative waveform shapes presented here-when scaled by an individual's cycle-averaged VFR-may be used to characterize normal ICA and VA flow rate dynamics. This capability may be of particular utility for studies where cerebrovascular flow dynamics are required, but only average flow rates are available.

Knowledge of human blood-flow waveforms is required for in vitro investigations and numerical modelling. Parameters of interest include: velocity and flow waveform shapes, inter- and intra-subject variability and frequency content. We characterized the blood-velocity waveforms in the left and right common carotid arteries (CCAs) of 17 normal volunteers (24 to 34 years), analysing 3560 cardiac cycles in total. Instantaneous peak-velocity (Vpeak) measurements were obtained using pulsed-Doppler ultrasound with simultaneous collection of ECG data. An archetypal Vpeak waveform was created using velocity and timing parameters at waveform feature points. We report the following timing (post-R-wave) and peak-velocity parameters: cardiac interbeat interval (T(RR)) = 0.917 s (intra-subject standard deviation = +/- 0.045 s); cycle-averaged peak-velocity (V(CYC)) = 38.8 cm s(-1) (+/-1.5 cm s(-1)); maximum systolic Vpeak = 108.2 cm s(-1) (+/-3.8 cm s(-1)) at 0.152 s (+/-0.008 s); dicrotic notch Vpeak = 19.4 cm s(-1) (+/-2.9 cm s(-1)) at 0.398 s (+/-0.007 s). Frequency components below 12 Hz constituted 95% of the amplitude spectrum. Flow waveforms were computed from Vpeak by analytical solution of Womersley flow conditions (derived mean flow = 6.0 ml s(-1)). We propose that realistic, pseudo-random flow waveform sequences can be generated for experimental studies by varying, from cycle to cycle, only T(RR) and V(CYC) of a single archetypal waveform.

Small animal imaging has a critical role in phenotyping, drug discovery, and in providing a basic understanding of mechanisms of disease. Translating imaging methods from humans to small animals is not an easy task. The purpose of this work is to review in vivo X-ray based small animal imaging, with a focus on in vivo micro-computed tomography (micro-CT) and digital subtraction angiography (DSA). We present the principles, technologies, image quality parameters and types of applications. We show that both methods can be used not only to provide morphological, but also functional information, such as cardiac function estimation or perfusion. Compared to other modalities, x-ray based imaging is usually regarded as being able to provide higher throughput at lower cost and adequate resolution. The limitations are usually associated with the relatively poor contrast mechanisms and potential radiation damage due to ionizing radiation, although the use of contrast agents and careful design of studies can address these limitations. We hope that the information will effectively address how x-ray based imaging can be exploited for successful in vivo preclinical imaging.

Small-animal imaging has become increasingly more important as transgenic and knockout mice are produced to model human diseases. One imaging technique that has emerged is microcomputed tomography (micro-CT). For live-animal imaging, the precision in the images will be determined by the x-ray dose given to the animal. As a result, we propose a simple method to predict the noise performance of an x-ray micro-CT system as a function of dose and image resolution. An ideal, quantum-noise limited micro-CT scanner, assumed to have perfect resolution and ideal efficiency, was modeled. Using a simplified model, the coefficient of variation (COV) of the linear attenuation coefficient was calculated for a range of entrance doses and isotropic voxel sizes. COV calculations were performed for the ideal case and with simulated imperfections in efficiency and resolution. Our model was validated in phantom studies and mouse images were acquired with a specimen scanner to illustrate the results. A simplified model of noise propagation in the case of isotropic resolution indicates that the COV in the linear attenuation coefficient is proportional to (dose)(-1/2) and to the (isotropic voxel size)(-2) in the reconstructed volume. Therefore an improvement in the precision can be achieved only by increasing the isotropic voxel size (thereby decreasing the resolution of the image) or by increasing the x-ray dose. For the ideal scanner, a COV of 1% in the linear attenuation coefficient for an image of a mouse exposed to 0.25 Gy is obtained with a minimum isotropic voxel size of 135 microm. However, the same COV is achieved at a dose of 5.0 Gy with a 65 microm isotropic voxel size. Conversely, for a 68 mm diameter rat, a COV of 1% obtained from an image at 5.0 Gy would require an isotropic voxel size of 100 microm. These results indicate that short-term, potentially lethal, effects of ionizing radiation will limit high-resolution live animal imaging. As improvements in detector technology allow the resolution to improve, by decreasing the detector element size to tens of microns or less, high quality images will be limited by the x-ray dose administered. For the highest quality images, these doses will approach the lethal dose or LD50 for the animals. Approaching the lethal dose will affect the way experiments are planned, and may reduce opportunities for experiments involving imaging the same animal over time. Dose considerations will become much more important for live small-animal imaging as the limits of resolution are tested.

The rabbit ACLT model of OA demonstrates progressive cartilage degeneration and intermediate bone changes at 4, 8, and 12 weeks post-surgery. Cartilage and bone lesions were characterized ex vivo using 4-T MRI and micro-CT, and MRI assessment of cartilage degeneration was correlated to macroscopic grading.

A supplemental appendix to this article is published electronically only at http://jdr.sagepub.com/supplemental. ABSTRACTBone sialoprotein (BSP) is an extracellular matrix protein found in mineralized tissues of the skeleton and dentition. BSP is multifunctional, affecting cell attachment and signaling through an RGD integrin-binding region, and acting as a positive regulator for mineral precipitation by nucleating hydroxyapatite crystals. BSP is present in cementum, the hard tissue covering the tooth root that anchors periodontal ligament (PDL) attachment. To test our hypothesis that BSP plays an important role in cementogenesis, we analyzed tooth development in a Bsp null ( -/-) mouse model. Developmental analysis by histology, histochemistry, and SEM revealed a significant reduction in acellular cementum formation on Bsp -/-mouse molar and incisor roots, and the cementum deposited appeared hypomineralized. Structural defects in cementum-PDL interfaces in Bsp -/-mice caused PDL detachment, likely contributing to the high incidence of incisor malocclusion. Loss of BSP caused progressively disorganized PDL and significantly increased epithelial down-growth with aging. Bsp -/-mice displayed extensive root and alveolar bone resorption, mediated by increased RANKL and the presence of osteoclasts. Results collected here suggest that BSP plays a non-redundant role in acellular cementum formation, likely involved in initiating mineralization on the root surface. Through its importance to cementum integrity, BSP is essential for periodontal function.KEY WORDS: bone sialoprotein, cementum, periodontal ligament, bone, alkaline phosphatase, extracellular matrix.

Small-animal imaging has recently become an area of increased interest because more human diseases can be modeled in transgenic and knockout rodents. As a result, micro-computed tomography (micro-CT) systems are becoming more common in research laboratories, due to their ability to achieve spatial resolution as high as 10 microm, giving highly detailed anatomical information. Most recently, a volumetric cone-beam micro-CT system using a flat-panel detector (eXplore Ultra, GE Healthcare, London, ON) has been developed that combines the high resolution of micro-CT and the fast scanning speed of clinical CT, so that dynamic perfusion imaging can be performed in mice and rats, providing functional physiological information in addition to anatomical information. This and other commercially available micro-CT systems all promise to deliver precise and accurate high-resolution measurements in small animals. However, no comprehensive quality assurance phantom has been developed to evaluate the performance of these micro-CT systems on a routine basis. We have designed and fabricated a single comprehensive device for the purpose of performance evaluation of micro-CT systems. This quality assurance phantom was applied to assess multiple image-quality parameters of a current flat-panel cone-beam micro-CT system accurately and quantitatively, in terms of spatial resolution, geometric accuracy, CT number accuracy, linearity, noise and image uniformity. Our investigations show that 3D images can be obtained with a limiting spatial resolution of 2.5 mm(-1) and noise of +/-35 HU, using an acquisition interval of 8 s at an entrance dose of 6.4 cGy.