Soenke H. Bartling

Small Animal Computed Tomography Imaging

Micro Computed Tomography (micro-CT) was suggested in biomedical research to investigate tissues and small animals. Its use to characterize bone structures, vessels (e.g. tumor vascularization), tumors and soft tissues such as lung parenchyma has been shown. When co-registered, micro-CT can add structural information to other small animal imaging modalities. However, due to fundamental CT principles, high-resolution imaging with micro-CT demands for high x-ray doses and long scan times to generate a sufficiently high signal-to-noise ratio. Long scan times in turn make the use of extravascular contrast agents difficult. Recently introduced flat-panel based mini-CT systems offer a valuable trade- off between resolution (~200 µm), scan time (0.5 s), applied x-ray dose and scan field-of-view. This allows for angiography scans and follow-up examinations using iodinated contrast agents having a similar performance compared to patient scans. Furthermore, dynamic examinations such as perfusion studies as well as retrospective motion gating are currently implemented using flat-panel CT. This review summarizes applications of experimental CT in basic research and provides an overview of current hardware developments making CT a powerful tool to study tissue morphology and function in small laboratory animals such as rodents.

Retrospective motion gating in small animal CT of mice and rats

Objectives:Implementation and evaluation of retrospective respiratory and cardiac gating of mice and rats using a flat-panel volume-CT prototype (fpVCT). Materials and Methods:Respiratory and cardiac gating was implemented by equipping a fpVCT with a small animal monitoring unit. ECG and breathing excursions were recorded and 2 binary gating signals derived. Mice and rats were scanned continuously over 80 seconds after administration of blood-pool contrast media. Projections were chosen to reconstruct volumes that fall within defined phases of the cardiac/respiratory cycle. Results:Multireader analysis indicated that in gated still images motion artifacts were strongly reduced and diaphragm, tracheobronchial tract, heart, and vessels sharply delineated. From 4D series, functional data such as respiratory tidal volume and cardiac ejection fraction were calculated and matched well with values known from literature. Discussion:Implementation of retrospective gating in fpVCT improves image quality and opens new perspectives for functional cardiac and lung imaging in small animals.

Intrinsic respiratory gating in small-animal CT

Gating in small-animal CT imaging can compensate artefacts caused by physiological motion during scanning. However, all published gating approaches for small animals rely on additional hardware to derive the gating signals. In contrast, in this study a novel method of intrinsic respiratory gating of rodents was developed and tested for mice (n=5), rats (n=5) and rabbits (n=2) in a flat-panel cone-beam CT system. In a consensus read image quality was compared with that of non-gated and retrospective extrinsically gated scans performed using a pneumatic cushion. In comparison to non-gated images, image quality improved significantly using intrinsic and extrinsic gating. Delineation of diaphragm and lung structure improved in all animals. Image quality of intrinsically gated CT was judged to be equivalent to extrinsically gated ones. Additionally 4D datasets were calculated using both gating methods. Values for expiratory, inspiratory and tidal lung volumes determined with the two gating methods were comparable and correlated well with values known from the literature. We could show that intrinsic respiratory gating in rodents makes additional gating hardware and preparatory efforts superfluous. This method improves image quality and allows derivation of functional data. Therefore it bears the potential to find wide applications in small-animal CT imaging.

Intrinsic gating for small-animal computed tomography: a robust ECG-less paradigm for deriving cardiac phase information and functional imaging.

Background—A projection-based method of intrinsic cardiac gating in small-animal computed tomography imaging is presented. Methods and Results—In this method, which operates without external ECG monitoring, the gating reference signal is derived from the raw data of the computed tomography projections. After filtering, the derived gating reference signal is used to rearrange the projection images retrospectively into data sets representing different time points in the cardiac cycle during expiration. These time-stamped projection images are then used for tomographic reconstruction of different phases of the cardiac cycle. Intrinsic gating was evaluated in mice and rats and compared with extrinsic retrospective gating. An excellent agreement was achieved between ECG-derived gating signal and self-gating signal (coverage probability for a difference between the 2 measurements to be less than 5 ms was 89.2% in mice and 85.9% in rats). Functional parameters (ventricular volumes and ejection fraction) obtained from the intrinsic and the extrinsic data sets were not significantly different. The ease of use and reliability of intrinsic gating were demonstrated via a chemical stress test on 2 mice, in which the system performed flawlessly despite an increased heart rate. Because of intrinsic gating, the image quality was improved to the extent that even the coronary arteries of mice could be visualized in vivo despite a heart rate approaching 430 bpm. Feasibility of intrinsic gating for functional imaging and assessment of cardiac wall motion abnormalities was successfully tested in a mouse model of myocardial infarction. Conclusions—Our results demonstrate that self-gating using advanced software postprocessing of projection data promises to be a valuable tool for rodent computed tomography imaging and renders ECG gating with external electrodes superfluous.

Gating in small-animal cardio-thoracic CT

Gating is necessary in cardio-thoracic small-animal imaging because of the physiological motions that are present during scanning. In small-animal computed tomography (CT), gating is mainly performed on a projection base because full scans take much longer than the motion cycle. This paper presents and discusses various gating concepts of small-animal CT, and provides examples of concrete implementation. Since a wide variety of small-animal CT scanner systems exist, scanner systems are discussed with respect to the most suitable gating methods. Furthermore, an overview is given of cardio-thoracic imaging and gating applications. The necessary contrast media are discussed as well as gating limitations. Gating in small-animal imaging requires the acquisition of a gating signal during scanning. This can be done extrinsically (additional hardware, e.g. electrocardiogram) or intrinsically from the projection data itself. The gating signal is used retrospectively during CT reconstruction, or prospectively to trigger parts of the scan. Gating can be performed with respect to the phase or the amplitude of the gating signal, providing different advantages and challenges. Gating methods should be optimized with respect to the diagnostic question, scanner system, animal model, type of narcosis and actual setup. The software-based intrinsic gating approaches increasingly employed give the researcher independence from difficult and expensive hardware changes.

Synthesis and characterization of Bi2O3/HSA core-shell nanoparticles for X-ray imaging applications.

Bismuth oxide nanoparticles of 12.1 ± 3.0 nm diameter were prepared by thermal decomposition of bismuth acetate dissolved in ethylene glycol in the presence of an oxidizing agent. Functionalization and stabilization of the hydrophobic Bi(2)O(3) nanoparticles was accomplished by coating these core nanoparticles with human serum albumin (HSA), via a precipitation process. The formed Bi(2)O(3)/HSA core-shell nanoparticles were of 15.2 ± 3.5 nm diameter. Elemental analysis measurements indicated that the bismuth weight % of the Bi(2)O(3)/HSA core-shell nanoparticles is 72.9. The crystalline structure of these nanoparticles was examined by XRD. The radiopacity of these nanoparticles was demonstrated in vitro and in vivo by a CT scanner. In ovo and in vivo trials proved the safety of these Bi(2)O(3)/HSA core-shell nanoparticles. In the future, we plan to extend this study particularly for molecular imaging applications.

Fully automated intrinsic respiratory and cardiac gating for small animal CT

A fully automated, intrinsic gating algorithm for small animal cone-beam CT is described and evaluated. A parameter representing the organ motion, derived from the raw projection images, is used for both cardiac and respiratory gating. The proposed algorithm makes it possible to reconstruct motion-corrected still images as well as to generate four-dimensional (4D) datasets representing the cardiac and pulmonary anatomy of free-breathing animals without the use of electrocardiogram (ECG) or respiratory sensors. Variation analysis of projections from several rotations is used to place a region of interest (ROI) on the diaphragm. The ROI is cranially extended to include the heart. The centre of mass (COM) variation within this ROI, the filtered frequency response and the local maxima are used to derive a binary motion-gating parameter for phase-sensitive gated reconstruction. This algorithm was implemented on a flat-panel-based cone-beam CT scanner and evaluated using a moving phantom and animal scans (seven rats and eight mice). Volumes were determined using a semiautomatic segmentation. In all cases robust gating signals could be obtained. The maximum volume error in phantom studies was less than 6%. By utilizing extrinsic gating via externally placed cardiac and respiratory sensors, the functional parameters (e.g. cardiac ejection fraction) and image quality were equivalent to this current gold standard. This algorithm obviates the necessity of both gating hardware and user interaction. The simplicity of the proposed algorithm enables adoption in a wide range of small animal cone-beam CT scanners.

Large gastrosplenic fistula after effective treatment of abdominal diffuse large-B-cell lymphoma

Dear Editor, The monoclonal antibody rituximab, which binds to the CD20 antigen expressed on normal B cells and the malignant cells of more than 90% of diffuse, large B-cell lymphomas demonstrated its efficacy as a single agent or in combination with chemotherapy (e.g., CHOP) without adding relevant toxicity [1]. Its potent efficacy in combination with CHOP, together with its favorable toxicity profile, establishes rituximab as an important part of modern standard immunochemotherapy of diffuse, large B-cell lymphomas. However, the potency of the combined treatment regime may cause severe side effects in case of infiltration of the gastric wall as described in our case. A 56-year-old man suffering from general weakness, obstipation, and a weight loss of 18 kg in the previous 3 months was admitted to our hospital to rule out cancer. The patient denied having any other symptoms (e.g., fever and sweating), and a recently performed colonoscopy was unremarkable. On initial abdominal sonography, a mass, 15 cm in diameter, was detected in the upper left quadrant. Subsequent computed tomography (CT) verified the presence of a tumor that infiltrated the spleen and had direct contact to the stomach. Although infiltration of the gastric wall was assumed, it could not be verified by CT (Fig. 1). No other abdominal tumor manifestations were found; the peripheral lymph nodes were unremarkable, and no pathologic findings were noted on bone marrow biopsy or on chest CT. Finally, CT-guided biopsy of the tumor led to the diagnosis of a diffuse large B-cell lymphoma (stage IIBE, IPI1). The patient was then treated according to the R-CHOP 21 regimen [2]. Several days after the end of the third cycle, the patient presented with fever and signs of acute infection. Follow-up CT showed complete remission which had resulted in a large opening in the stomach wall (Fig. 2). The patient was referred to surgery and underwent splenectomy with resection of the greater curvature of the stomach. Histopathologic analysis revealed normal splenic parenchyma and gastric tissue with necrotic areas but only avital tumor cells were found. The patient recovered well, was discharged on day 12 after surgery, and received the remaining cycles of chemotherapy. Gastrosplenic fistula resulting from a gastric or splenic lesion is a rare entity. Gastric adenocarcinoma, Crohn’s disease, benign gastric ulcer, and splenic lymphoma are known causes [3]. For a gastrosplenic fistula to develop in a splenic lymphoma, invasion of the gastric wall is required. If most or even all gastric wall layers are infiltrated, rapid necrosis of the tumor tissue may result in the formation of a fistula to the adjacent spleen [4]. In this context, five cases of gastrosplenic fistula occurring after chemotherapy have been reported [5], most of them describing the formation of quite small fistula. However, if a larger part of the stomach is infiltrated, it is possible for a large opening in the stomach wall to arise, as reported in our case. Ann Hematol (2008) 87:337–338 DOI 10.1007/s00277-007-0404-5

Intrarenal Artery Delineation With Ultra High Resolution, Flat Panel Based, Volume Computerized Tomography: Outer Limits of Spatial Resolution

PURPOSEnNew methods of noninvasive high resolution imaging may improve the delineation of tumor microvessels and, thus, be of significant help in surgical planning and cost-effective monitoring of novel anti-angiogenic therapy. We determined the maximum delineation of intrarenal microvessels with a novel flat panel based volume computerized tomography system in an experimental setting.nnnMATERIALS AND METHODSnWe prospectively evaluated 13 porcine renal specimens for intrarenal vessel delineation using a prototype gantry based, flat panel, cone beam computerized tomography system. The gantry incorporates an array of a 40 x 30 cm(2) CsI amorphous silicon flat panel detector consisting of a 2,048 x 1,536 matrix. After catheterizing the renal artery with a 5Fr end hole catheter a contrast enhanced scan was performed using BaS as contrast medium at a dilution of 200 mg/ml. The diameter of all definable arterial branches was determined using a software tool based on Medical Imaging and Interaction Toolkit, allowing semi-automatic segmentation of the vessel tree. In step 1 the vessel tree is segmented by a 3-dimensional region growing algorithm. Following its medial axis the vessel tree is extracted and converted to a representation, including the diameter of the vessels.nnnRESULTSnIn each kidney an average +/- SD of 47,454 +/- 22,382 arterial branches could be delineated. The diameter of the branches was 0.029 (mean 0.032 +/- 0.0025) to 3.444 mm (mean 1.813 +/- 0.6139) with a median of 0.263 mm. Of visible intrarenal arteries 2.7% had a vessel diameter of 0.029 mm.nnnCONCLUSIONSnFlat panel based volume computerized tomography can visualize intrarenal microvessels down to a diameter of 0.03 mm. It may improve the assessment of renal microvessel architecture in healthy patients and in those with pathological conditions.