Simultaneous Multiparametric PET/MRI with Silicon Photomultiplier PET and Ultra-High-Field MRI for Small-Animal Imaging.

UNLABELLED: Visualization of biologic processes at molecular and cellular levels has revolutionized the understanding and treatment of human diseases. However, no single biomedical imaging modality provides complete information, resulting in the emergence of multimodal approaches. Combining state-of-the-art PET and MRI technologies without loss of system performance and overall image quality can provide opportunities for new scientific and clinical innovations. Here, we present a multiparametric PET/MR imager based on a small-animal dedicated, high-performance, silicon photomultiplier (SiPM) PET system and a 7-T MR scanner. METHODS: A SiPM-based PET insert that has the peak sensitivity of 3.4% and center volumetric resolution of 1.92/0.53 mm(3) (filtered backprojection/ordered-subset expectation maximization) was developed. The SiPM PET insert was placed between the mouse body transceiver coil and gradient coil of a 7-T small-animal MRI scanner for simultaneous PET/MRI. Mutual interference between the MRI and SiPM PET systems was evaluated using various MR pulse sequences. A cylindric corn oil phantom was scanned to assess the effects of the SiPM PET on the MR image acquisition. To assess the influence of MRI on the PET imaging functions, several PET performance indicators including scintillation pulse shape, flood image quality, energy spectrum, counting rate, and phantom image quality were evaluated with and without the application of MR pulse sequences. Simultaneous mouse PET/MRI studies were also performed to demonstrate the potential and usefulness of the multiparametric PET/MRI in preclinical applications. RESULTS: Excellent performance and stability of the PET system were demonstrated, and the PET/MRI combination did not result in significant image quality degradation of either modality. Finally, simultaneous PET/MRI studies in mice demonstrated the feasibility of the developed system for evaluating the biochemical and cellular changes in a brain tumor model and facilitating the development of new multimodal imaging probes. CONCLUSION: We developed a multiparametric imager with high physical performance and good system stability and demonstrated its feasibility for small-animal experiments, suggesting its usefulness for investigating in vivo molecular interactions of metabolites, and cross-validation studies of both PET and MRI.

Effect of anisotropy and spatial compound imaging on renal cortical echogenicity in dogs.

The echogenicity of the renal cortex is an important parameter to consider in dogs that are suspected to have renal dysfunction. Focal increases in echogenicity have been attributed to neoplasia, infection, calcification, fibrosis, gas, and infarction. Anisotropic backscatter has been described as a source of focally increased renal cortical echogenicity in several species. The source of anisotropy appears to be the medullary rays, which are oriented perpendicular to the renal capsule. Spatial compound imaging (SCI) is an ultrasound setting that uses beam steering to acquire and average several overlapping scans of an object from different view angles, creating a compound image that is updated in real time. The impact of insonation angle and SCI on renal cortical echogenicity was evaluated ex vivo in eight kidneys from four dogs. Significant angle-dependent differences in cortical echogenicity were detected with both microconvex and linear transducers (P < 0.0001). Furthermore, the angle-dependent echogenicity differences persisted when SCI mode was used. Our finding that echogenicity was increased using a perpendicular insonation angle (90°) relative to the tubules, compared to a parallel insonation angle (0°) should assist in the interpretation of ultrasonographic images of the dog kidney.

Hybrid small animal imaging system combining magnetic resonance imaging with fluorescence tomography using single photon avalanche diode detectors.

The high sensitivity of fluorescence imaging enables the detection of molecular processes in living organisms. However, diffuse light propagation in tissue prevents accurate recovery of tomographic information on fluorophore distribution for structures embedded deeper than 0.5 mm. Combining optical with magnetic resonance imaging (MRI) provides an accurate anatomical reference for fluorescence imaging data and thereby enables the correlation of molecular with high quality structural/functional information. We describe an integrated system for small animal imaging incorporating a noncontact fluorescence molecular tomography (FMT) system into an MRI detector. By adopting a free laser beam design geometrical constraints imposed by the use of optical fibers could be avoided allowing for flexible fluorescence excitation schemes. Photon detection based on a single-photon avalanche diode array enabled simultaneous FMT/MRI measurements without interference between modalities. In vitro characterization revealed good spatial accuracy of FMT data and accurate quantification of dye concentrations. Feasibility of FMT/MRI was demonstrated in vivo by simultaneous assessment of protease activity and tumor morphology in murine colon cancer xenografts.

High-resolution adaptive PET imaging.

While the performance of small animal PET systems has been improved impressively in terms of spatial resolution and sensitivity, demands for further improvements remain high with growing number of applications. Here we propose a novel PET system design that integrates a high-resolution detector into an existing PET system to obtain higher-resolution images in a target region. The high-resolution detector will be adaptively positioned based on the detectability or quantitative accuracy of a feature of interest. The proposed system will be particularly effective for studying human cancers using animal models where tumors are often grown near the skin surface and therefore permit close contact with the high resolution detector. It will also be useful for the high-resolution brain imaging in rodents. In this paper, we present the theoretical analysis and Monte Carlo simulation studies of the performance of the proposed system.

Design and evaluation of a low-cost respiratory monitoring device for use with anaesthetized animals.

This report describes a simple, non-invasive electronic device that employs a compact accelerometer integrated circuit to transduce movements in the chest wall of an anaesthetized animal into an analogue signal that can be used to calculate the rate and relative depth of respiration. The device requires amplification by signal processing hardware/software which are common to most experimental laboratories. We assessed the sensitivity of the device by its ability to detect changes in respiratory patterns produced by modulating the depth of anaesthesia in isoflurane-anaesthetized Wistar rats. It is widely accepted that many anaesthetic agents affect respiratory patterns, especially respiratory rate (RR), which is often used as an important index of anaesthetic depth. Respiratory parameters obtained with the device were compared with concurrently recorded electroencephalographic and cardiac measures. Different concentrations of anaesthetic agent produced four depths of anaesthesia, identified using established electroencephalographic criteria. The accelerometer was attached easily and securely to the location of maximal chest wall movement and produced a strong respiratory signal that was detectable in all four anaesthetic stages. Deepening the anaesthesia produced a gradual decrease in RR, a decrease in dominant spectral frequency of the electroencephalogram (EEG) but no change in the heart rate. There was a significant correlation between RR and the dominant spectral frequency of the EEG, indicating that one useful application of the monitor could be to identify anaesthetic stages. The results demonstrate that respiratory parameters can be recorded using a simply constructed, low-cost device and suggest an application in the monitoring of anaesthetic depth.

Calcium sensitivity of force production and myofibrillar ATPase activity in muscles from Thoroughbreds with recurrent exertional rhabdomyolysis.

OBJECTIVE: To determine whether the basis for recurrent exertional rhabdomyolysis (RER) in Thoroughbreds lies in an alteration in the activation and regulation of the myofibrillar contractile apparatus by ionized calcium. ANIMALS: 4 Thoroughbred mares with RER and 4 clinically normal (control) Thoroughbreds. PROCEDURES: Single chemically-skinned type-I (slow-twitch) and type-II (fast-twitch) muscle fibers were obtained from punch biopsy specimens, mounted to a force transducer, and the tensions that developed in response to a series of calcium concentrations were measured. In addition, myofibril preparations were isolated from muscle biopsy specimens and the maximal myofibrillar ATPase activity, as well as its sensitivity to ionized calcium, were measured. RESULTS: Equine type-I muscle fibers were more readily activated by calcium than were type-II muscle fibers. However, there was no difference between the type-II fibers of RER-affected and control horses in terms of calcium sensitivity of force production. There was also no difference between muscle myofibril preparations from RER-affected and control horses in calcium sensitivity of myofibrillar ATPase activity. CONCLUSIONS AND CLINICAL RELEVANCE: An alteration in myofibrillar calcium sensitivity is not a basis for pathologic contracture development in muscles from RER-affected horses. Recurrent exertional rhabdomyolysis in Thoroughbreds may represent a novel heritable defect in the regulation of muscle excitation-contraction coupling or myoplasmic calcium concentration.

Urocystolith detection: comparison of survey, contrast radiographic and ultrasonographic techniques in an in vitro bladder phantom.

Urocystoliths of 9 mineral types from 437 canine patients submitted to the University of Minnesota Urolith Bank were imaged in a urinary bladder phantom. Imaging techniques simulated were survey radiography, pneumocystography, double contrast cystography (two iodine concentrations) and real-time ultrasonography (3.5 MHz, 5.0 MHz, 7.5 MHz). Imaging techniques were compared for accuracy of urocystolith detection, accuracy of urocystolith enumeration, and tendencies for over or undercounting. Across urocystolith mineral types, the false negative rates (no urocystoliths detected in a given case) for survey radiographs range from 2 to 27%. Pneumocystographic techniques are one-half as likely to yield false negative results as are survey radiographic techniques. Underestimates of urocystolith numbers and false negatives are likely using 80 mg iodine/ml double contrast cystography because calcium-based urocystoliths are isopaque in this contrast medium dilution. The 200 mg iodine/ml double contrast cystographic techniques are unlikely to yield false negative diagnoses even for very small (< or = 1.0 mm) urocystoliths and is comparable to pneumocystography for detection and slightly better for enumeration. The likelihood of an ultrasonographic false negative for urocystoliths decreases with increasing MHz. Under optimal conditions using a 7.5 MHz mechanical sector transducer, the false negative rates were comparable to double contrast cystography, but rates increased notably with lower MHz transducers.

La glándula de Harder: un transductor neuroinmunoendrocrino / The Harderian gland: neuroinmunoendrocrine transductor

La glándula de Harder es una glándula túbulo-alveolar localizada en la parte posterior de la órbita ocular de animales que poseen membrana nictitante. En estos mamiferos la glándula contiene una gran cantidad de lípidos. La glándula de Harder de roedores contiene un pigmento café rojizo, el cual ha sido identificado como porfirina. Las funciones de la glándula de Harder son; síntesis y liberación de ferhormonas, fotoprotección y termorregulación, osmoprotección y se le ha propuesto además un papel inmunoendocrino

The action of low dose endotoxin on equine bowel motility.

Post operative ileus (POI) is a common and serious complication of colic surgery in the horse. There is a high correlation between the incidence of POI and the presence of ischaemic bowel, suggesting a role for endotoxin. 0.1 micrograms/kg endotoxin was administered intravenously to six ponies with chronically implanted gastrointestinal electromechanical recording devices. It produced profound disruption of normal fasting bowel motility patterns, with an inhibition of gastric contraction amplitude and rate, left dorsal colon contraction product and small colon spike rate. In the small intestine an increase in abnormally arranged regular activity and a decrease in irregular activity was observed. There was no significant prolongation in stomach to anus transit time as assessed by the passage of plastic spheres. The bowel motility patterns induced by endotoxin could be mimicked by the intravenous infusion of PGE2 and less potently by PGI2 (prostacyclin), but not by PGF2 alpha. This study provides evidence that systematic endotoxin present in clinical cases of colic may play a role in the pathogenesis of equine ileus. The acute effects of endotoxin on bowel motility appear to be mediated indirectly by prostaglandins, and the inhibitory effects may be mediated mainly by PGE2.