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Background Two-dimensional (2D) specimen radiography (SR) and tomosynthesis (DBT) for breast cancer yield data that lack high-depth resolution. A volumetric specimen imager (VSI) was developed to provide full-3D and thin-slice cross-sectional visualization at a 360° view angle. The purpose of this prospective trial was to compare VSI, 2D SR, and DBT interpretation of lumpectomy margin status with the final pathologic margin status of breast lumpectomy specimens. Methods The study enrolled 200 cases from two institutions. After standard imaging and interpretation was performed, the main lumpectomy specimen was imaged with the VSI device. Image interpretation was performed by three radiologists after surgery based on VSI, 2D SR, and DBT. A receiver operating characteristic (ROC) curve was created for each method. The area under the curve (AUC) was computed to characterize the performance of the imaging method interpreted by each user. Results From 200 lesions, 1200 margins were interpreted. The AUC values of VSI for the three radiologists were respectively 0.91, 0.90, and 0.94, showing relative improvement over the AUCs of 2D SR by 54%, 13%, and 40% and DBT by 32% and 11%, respectively. The VSI has sensitivity ranging from 91 to 94%, specificity ranging from 81 to 85%, a positive predictive value ranging from 25 to 30%, and a negative predicative value of 99%. Conclusions The ROC curves of the VSI were higher than those of the other specimen imaging methods. Full-3D specimen imaging can improve the correlation between the main lumpectomy specimen margin status and surgical pathology. The findings from this study suggest that using the VSI device for intraoperative margin assessment could further reduce the re-excision rates for women with malignant disease.

Rationale: Pulmonary arterial hypertension (PAH) is a proliferative arteriopathy associated with glucose transporter-1 (Glut1) up-regulation and a glycolytic shift in lung metabolism. Glycolytic metabolism can be detected with the positron emission tomography (PET) tracer 18F-fluorodeoxyglucose (FDG).Objectives: The precise cell type in which glycolytic abnormalities occur in PAH is unknown. Moreover, whether FDG-PET is sufficiently sensitive to monitor PAH progression and detect therapeutic regression is untested. We hypothesized that increased lung FDG-PET reflects enhanced glycolysis in vascular cells and is reversible in response to effective therapies.Methods: PAH was induced in Sprague-Dawley rats by monocrotaline or chronic hypoxia (10% oxygen) in combination with Sugen 5416. Monocrotaline rats were treated with oral dichloroacetate or daily imatinib injections. FDG-PET scans and pulmonary artery acceleration times were obtained weekly. The origin of the PET signal was assessed by laser capture mic...

Mitochondria exist in dynamic networks that undergo fusion and fission. Mitochondrial fusion and fission are mediated by several GTPases in the outer mitochondrial membrane, notably mitofusin-2 (Mfn-2), which promotes fusion, and dynamin-related protein (Drp-1), which promotes fission. We report that human lung cancer cell lines exhibit an imbalance of Drp-1/Mfn-2 expression, which promotes a state of mitochondrial fission. Lung tumor tissue samples from patients demonstrated a similar increase in Drp-1 and decrease in Mfn-2 when compared to adjacent healthy lung. Complementary approaches to restore mitochondrial network formation in lung cancer cells by overexpression of Mfn-2, Drp-1 inhibition, or Drp-1 knockdown resulted in a marked reduction of cancer cell proliferation and an increase in spontaneous apoptosis. The number of cancer cells in S phase decreased from 32.4 ± 0.6 to 6.4 ± 0.3% with Drp-1 inhibition (P

The etiology of hepatopulmonary syndrome (HPS), a common complication of cirrhosis, is unknown. Inflammation and macrophage accumulation occur in HPS; however, their importance is unclear. Common bile duct ligation (CBDL) creates an accepted model of HPS, allowing us to investigate the cause of HPS.We hypothesized that macrophages are central to HPS and investigated the therapeutic potential of macrophage depletion.Hemodynamics, alveolar-arterial gradient, vascular reactivity, and histology were assessed in CBDL versus sham rats (n = 21 per group). The effects of plasma on smooth muscle cell proliferation and endothelial tube formation were measured. Macrophage depletion was used to prevent (gadolinium) or regress (clodronate) HPS. CD68(+) macrophages and capillary density were measured in the lungs of patients with cirrhosis versus control patients (n = 10 per group).CBDL increased cardiac output and alveolar-arterial gradient by causing capillary dilatation and arteriovenous malformations. Activated CD68(+)macrophages (nuclear factor-κB+) accumulated in HPS pulmonary arteries, drawn by elevated levels of plasma endotoxin and lung monocyte chemoattractant protein-1. These macrophages expressed inducible nitric oxide synthase, vascular endothelial growth factor, and platelet-derived growth factor. HPS plasma increased endothelial tube formation and pulmonary artery smooth muscle cell proliferation. Macrophage depletion prevented and reversed the histological and hemodynamic features of HPS. CBDL lungs demonstrated increased medial thickness and obstruction of small pulmonary arteries. Nitric oxide synthase inhibition unmasked exaggerated pulmonary vasoconstrictor responses in HPS. Patients with cirrhosis had increased pulmonary intravascular macrophage accumulation and capillary density.HPS results from intravascular accumulation of CD68(+)macrophages. An occult proliferative vasculopathy may explain the occasional transition to portopulmonary hypertension. Macrophage depletion may have therapeutic potential in HPS.

Efficient osteogenic differentiation and bone formation from mesenchymal stem cells (MSCs) should have clinical applications in treating nonunion fracture healing. MSCs are adherent bone marrow stromal cells that can self-renew and differentiate into osteogenic, chondrogenic, adipogenic, and myogenic lineages. We have identified bone morphogenetic protein 9 (BMP-9) as one of the most osteogenic BMPs. Here we investigate the effect of insulin-like growth factor 2 (IGF-2) on BMP-9-induced bone formation. We have found that endogenous IGF-2 expression is low in MSCs. Expression of IGF-2 can potentiate BMP-9-induced early osteogenic marker alkaline phosphatase (ALP) activity and the expression of later markers. IGF-2 has been shown to augment BMP-9-induced ectopic bone formation in the stem cell implantation assay. In perinatal limb explant culture assay, IGF-2 enhances BMP-9-induced endochondral ossification, whereas IGF-2 itself can promote the expansion of the hypertropic chondrocyte zone of the cultured limb explants. Expression of the IGF antagonists IGFBP3 and IGFBP4 leads to inhibition of the IGF-2 effect on BMP-9-induced ALP activity and matrix mineralization. Mechanistically, IGF-2 is further shown to enhance the BMP-9-induced BMPR-Smad reporter activity and Smad1/5/8 nuclear translocation. PI3-kinase (PI3K) inhibitor LY294002 abolishes the IGF-2 potentiation effect on BMP-9-mediated osteogenic signaling and can directly inhibit BMP-9 activity. These results demonstrate that BMP-9 crosstalks with IGF-2 through PI3K/AKT signaling pathway during osteogenic differentiation of MSCs. Taken together, our findings suggest that a combination of BMP-9 and IGF-2 may be explored as an effective bone-regeneration agent to treat large segmental bony defects, nonunion fracture, and/or osteoporotic fracture. © 2010 American Society for Bone and Mineral Research.

To study the feasibility of using 2-deoxy-D-glucose (2-DG)-labeled gold nanoparticle (AuNP-DG) as a computed tomography (CT) contrast agent with tumor targeting capability through in vitro experiments.Gold nanoparticles (AuNP) were fabricated and were conjugated with 2-deoxy-D-glucose. The human alveolar epithelial cancer cell line, A-549, was chosen for the in vitro cellular uptake assay. Two groups of cell samples were incubated with the AuNP-DG and the unlabeled AuNP, respectively. Following the incubation, the cells were washed with sterile PBS to remove the excess gold nanoparticles and spun to cell pellets using a centrifuge. The cell pellets were imaged using a microCT scanner immediately after the centrifugation. The reconstructed CT images were analyzed using a commercial software package.Significant contrast enhancement in the cell samples incubated with the AuNP-DG with respect to the cell samples incubated with the unlabeled AuNP was observed in multiple CT slices.Results from this study demonstrate enhanced uptake of 2-DG-labeled gold nanoparticle by cancer cells in vitro and warrant further experiments to study the exact molecular mechanism by which the AuNP-DG is internalized and retained in the tumor cells.

Osteosarcoma (OS) is the most common primary malignancy of bone. There is a critical need to identify the events that lead to the poorly understood mechanism of OS development and metastasis. The goal of this investigation is to identify and characterize a novel marker of OS progression. We have established and characterized a highly metastatic OS subline that is derived from the less metastatic human MG63 line through serial passages in nude mice via intratibial injections. Microarray analysis of the parental MG63, the highly metastatic MG63.2 subline, as well as the corresponding primary tumors and pulmonary metastases revealed insulin-like growth factor binding protein 5 (IGFBP5) to be one of the significantly downregulated genes in the metastatic subline. Confirmatory quantitative RT-PCR on 20 genes of interest demonstrated IGFBP5 to be the most differentially expressed and was therefore chosen to be one of the genes for further investigation. Adenoviral mediated overexpression and knockdown of IGFBP5 in the MG63 and MG63.2 cell lines, as well as other OS lines (143B and MNNG/HOS) that are independent of our MG63 lines, were employed to examine the role of IGFBP5. We found that overexpression of IGFBP5 inhibited in vitro cell proliferation, migration and invasion of OS cells. Additionally, IGFBP5 overexpression promoted apoptosis and cell cycle arrest in the G1 phase. In an orthotopic xenograft animal model, overexpression of IGFBP5 inhibited OS tumor growth and pulmonary metastases. Conversely, siRNA-mediated knockdown of IGFBP5 promoted OS tumor growth and pulmonary metastases in vivo. Immunohistochemical staining of patient-matched primary and metastatic OS samples demonstrated decreased IGFBP5 expression in the metastases. These results suggest 1) a role for IGFBP5 as a novel marker that has an important role in the pathogenesis of OS, and 2) that the loss of IGFBP5 function may contribute to more metastatic phenotypes in OS.

Craniosynostosis is a significant disorder affecting 1 in 2500 live births worldwide. Although a large body of work has focused on dural regulation and the contributions of molecular mediators such as fibroblast growth factor, bone morphogenetic protein, and transforming growth factor β, minimal attention has been directed toward osteoclast function in cranial suture biology. Receptor activator of nuclear factor κB (RANK) is an essential mediator of osteoclastogenesis and osteoclast activation. In this study, physiologic fusion of posterior frontal sutures in murine development correlated with decreasing protein expression of RANK in comparison to age-matched coronal and sagittal sutures via immunohistochemical survey. However, RANK mRNA did not exhibit a similar pattern suggesting that RANK is regulated at the protein level. Fused cranial sutures in nonsyndromic craniosynostotic children also showed decreased levels of RANK staining in immunohistochemistry in comparison to patent sutures from the same patients. Immunohistochemistry with a RANK ligand antibody did not show differences in fused or patent sutures. Moreover, RANK knockdown in calvarial strip suture cultures displayed increased bone density specifically in the suture line after infection with small interfering RANK viruses. Cranial suture biology, similar to bone biology in general, likely depends on a complex interplay between osteoblasts and osteoclasts. We now report a temporospatial correlation between RANK expression and suture morphology that suggests that osteoclast activity is important in maintenance of cranial suture patency in normal physiology and disease. Furthermore, RANK downregulation promoted suture fusion establishing a causal relationship between the presence of RANK and patency.

The purpose of this study was to investigate the feasibility of using a 2-deoxy-d-glucose (2-DG) labeled gold nanoparticle (AuNP-2-DG) as a functionally targeted computed tomography (CT) contrast agent to obtain high-resolution metabolic and anatomic information of tumor in a single CT scan. Gold nanoparticles (AuNPs) were fabricated and were conjugated with 1-DG or 2-DG. 1-DG provides an excellent comparison since it is known to interfere with the ability of the glucose transporter to recognize the sugar moiety. The human alveolar epithelial cancer cell line, A-549, was chosen for the in vitro cellular uptake assay. Three groups of cell samples were incubated with the 1-DG or 2-DG labeled AuNP and the unlabeled AuNP. Following the incubation, the cells were washed with sterile phosphate buffered saline to remove the excess AuNPs and spun using a centrifuge. The cell pellets were imaged using a microCT scanner immediately after the centrifugation. Internalization of AuNP-2-DG is verified using transmission electron microscopy imaging. Significant contrast enhancement in the cell samples incubated with the AuNP-2-DG with respect to the cell samples incubated with the unlabeled AuNP and the AuNP-1-DG was observed in multiple CT slices. Results from our in vitro experiments suggest that the AuNP-2-DG may be used as a functional CT contrast agent to provide high-resolution metabolic and anatomic information in a single CT scan. These results justify further in vitro and in vivo experiments to study the feasibility of using the AuNP-2-DG as a functional CT contrast agent in radiation therapy settings.

Right ventricular hypertrophy (RVH) and RV failure contribute to morbidity and mortality in pulmonary arterial hypertension (PAH). The cause of RV dysfunction and the feasibility of therapeutically targeting the RV are uncertain. We hypothesized that RV dysfunction and electrical remodeling in RVH result, in part, from a glycolytic shift in the myocyte, caused by activation of pyruvate dehydrogenase kinase (PDK). We studied two complementary rat models: RVH + PAH (induced by monocrotaline) and RVH + without PAH (induced by pulmonary artery banding (PAB)). Monocrotaline RVH reduced RV O(2)-consumption and enhanced glycolysis. RV 2-fluoro-2-deoxy-glucose uptake, Glut-1 expression, and pyruvate dehydrogenase phosphorylation increased in monocrotaline RVH. The RV monophasic action potential duration and QT(c) interval were prolonged due to decreased expression of repolarizing voltage-gated K(+) channels (Kv1.5, Kv4.2). In the RV working heart model, the PDK inhibitor, dichloroacetate, acutely increased glucose oxidation and cardiac work in monocrotaline RVH. Chronic dichloroacetate therapy improved RV repolarization and RV function in vivo and in the RV Langendorff model. In PAB-induced RVH, a similar reduction in cardiac output and glycolytic shift occurred and it too improved with dichloroacetate. In PAB-RVH, the benefit of dichloroacetate on cardiac output was approximately 1/3 that in monocrotaline RVH. The larger effects in monocrotaline RVH likely reflect dichloroacetate's dual metabolic benefits in that model: regression of vascular disease and direct effects on the RV. Reduction in RV function and electrical remodeling in two models of RVH relevant to human disease (PAH and pulmonic stenosis) result, in part, from a PDK-mediated glycolytic shift in the RV. PDK inhibition partially restores RV function and regresses RVH by restoring RV repolarization and enhancing glucose oxidation. Recognition that a PDK-mediated metabolic shift contributes to contractile and ionic dysfunction in RVH offers insight into the pathophysiology and treatment of RVH.

MicroCT small animal 3D angiography has various applications such as tumor growth evaluation or quantification of the pulmonary arterial tree morphometry. Due to longer acquisition times using preclinical systems, classical contrast agents are of little use in-vivo. Novel contrast agents such as gold nanoparticles and iodinated liposomes offer a possible solution to this difficulty by preventing rapid renal excretion. To evaluate different contrast agents, we filled pieces of polymer tubing (20 AWG) with solutions of 10 mg Au/ml and 30 mg Au/ml home-made gold nanoparticles, commercial gold nanoparticle (120 mg Au/ml), commercial iodinated liposomes, 30% barium sulfate solution, 6% iodine contrast solution and 100% saline (PBS), respectively. Each piece of tubing was imaged in our microCT together with the PBS filled tubing using identical imaging settings. Upon quantification and comparison of the phantom data, we imaged mice after injection of contrast agent. We also acquired data from excised lungs filled with contrast agent and gelatin solution. The barium sulfate solution had the highest measured radiodensity, which was 8 times higher than PBS. The solution with only 6% of iodine contrast gave us an increased radiodensity of 1.5x. Among the in-vivo compounds, the liposomal contrast agent had the highest radiodensity with 5 times than PBS, where the gold nanoparticles (10 mg/ml) were almost indistinguishable from PBS, but the higher concentrations show improvements in contrast. Our comparison shows that the traditional contrast agents have a higher radiodensity than novel compounds currently under development. Angiography using barium sulfate is a terminal experiment where the iodine contrast agent is cleared too quickly by the kidneys to be useful in-vivo. The small contrast improvement of the gold nanoparticles indicate that further development is still necessary for the particles to by useful in 3D angiography. In contrast, liposomal contrast agents appear to have reached a state where they can successfully highlight vessels in-vivo.

The bronchial circulation provides the lung with an oxygenated blood supply, derived from the aorta, whose primary purpose under normal conditions is thought to be nourishment of the airway walls +Guyton, 1996-. However,the study of the bronchial circulation and its development is particularly important with regard to lung tumors whose blood supply is via the bronchial circulation rather than the pulmonary circulation +Hirsch, 2001, Ohta, 2002-. Thus, we have developed a rat model of bronchial circulation angiogenesis,induced by complete occlusion of the left pulmonary artery. We have been observing the resulting perfusion changes in the left lung using dual-modality SPECT/micro-CT imaging. The initial objective of this study is to develop the necessary imaging system, protocol, and analysis methods for determining the time course of this angiogenesis, with the subsequent goal of using this approach to study the particular angiogenic mechanisms that might be involved.

Small animal SPECT using low energy photons of I-125 and approaching resolutions of microscopic levels, imaging parameters such as pinhole edge penetration, detector blur, geometric response, detector and pinhole misalignment, and gamma photon attenuation and scatter can have increasingly noticeable and/or adverse effects on reconstructed image quality. Iterative reconstruction algorithms, the widelyaccepted standard for emission tomography, allow modeling of such parameters through a system matrix. For this Monte Carlo simulation study, non-uniform attenuation correction was added to the existing system model. The model was constructed using ray-tracing and further included corrections for edge penetration, detector blur, and geometric aperture response. For each ray passing through different aperture locations, this method attenuates a voxel's contribution to a detector element along the photon path, which is then weighted according to a pinhole penetration model. To lower the computational and memory expenses, symmetry along the detector axes and an incremental storage scheme for the system model were used. For evaluating the nonuniform attenuation correction method, 3 phantoms were designed of which projection images were simulated using Monte Carlo methods. The first phantom was used to examined skin artifacts, the second to simulate attenuation by bone, and the third to generate artifacts of an air-filled space surrounded by soft tissue. In reconstructions without attenuation correction, artifacts were observed with up to a 40% difference in activity. These could be corrected using the implemented method, although in one case overcorrection occurred. Overall, attenuation correction improved reconstruction accuracy of the radioisotope distribution in the presence of structural differences.

Recent improvements in detector technology allow pinhole SPECT to approach spatial resolutions as low as 50 mum. Such high resolutions require a high accuracy of the imaging gantry for preclinical SPECT systems, and is not easily achieved in a laboratory setting. Analytical calibration methods are deemed to fail due to practical implications such as size and activity concentrations of the required point sources. Thus, we have developed a numerical calibration method based on least-square optimization that incorporates the modeling attributes of a forward projector frequently used in iterative reconstruction. The forward projector is currently capable of modeling detector misalignment such as detector rotation and pinhole translation, and will incorporate the pinhole point spread function as well as the size and shape of the point source. Currently, our calibration phantom consists of a single point source, positioned off-center in the object space. The optimization method involves a sequentially fitting of each individual parameter to the data, followed by fitting multiple parameters simultaneous in consecutive steps including all five parameters for the final fitting. The results of the optimization show an error of expected magnitude considering the relatively coarse sampling grid of our simulations. The relatively slow convergence of the y- and z-tilt require simulation of additional point sources. Further improvements of computational and memory efficiency need to be made, which enable the method to fit high resolution data as well as incorporation of the pinhole point spread function and the shape and size of the point sources.

To reduce scanning time in SPECT brain imaging, we investigate new brain imaging procedures, that include both scanning protocols and image processing methods, while at the same time, retain the comparable image quality for brain SPECT study. We apply our previously proposed fast convergent reconstruction along with some post-processing methods for the few view data. In the preliminary results from our simulations and physical phantom studies, the mean reconstructed ROI to background (R/B) ratio remains relatively stable with few variation. This result illustrates that a substantial saving of acquisition time can be achieved by reducing the number of projection views in the brain SPECT studies. The result is achieved without a significant loss in quantitative accuracy by using an improved reconstruction method in combination with additional data processing procedures.

Most partial volume correction (PVC) methods are ROI-based, and assume uniform activity within each ROI. Here, we extended a PVC method, developed by Rousset et al (JNM, 1998) called geometric transfer matrix (GTM), to a voxel-based PVC approach called v-GTM which accounts non-uniform activity within each ROI. The v-GTM method was evaluated using simulated data (perfect co-registered MRIs). We investigated the influence of noise, the effect of compensating detector response during iterative reconstruction methods and the effect of non-uniform activity. For simulated data, noise did not affect the accuracy of v-GTM method seriously. When detector response compensation was applied in iterative reconstruction, both PVC methods did not improve the recovery values. In the non-uniform experiment, v-GTM had slightly better recovery values and less bias than those of GTM. Conclusion: v-GTM resulted better recovery values, and might be useful for PVC in small regions of interest.

Iterative reconstruction of pinhole SPECT projection data acquired in preclinical animal imaging research benefits from modeling physical parameters of the imaging process. In this study, we developed a ray-driven system model that accounts for detector blur, the geometric response and edge penetration of the pinhole. GATE 2.2.0/GEANT 4 Monte Carlo simulations utilizing a tungsten knife-edge pinhole with an aperture diameter of 2 mm were applied to measure the pinhole point spread function (PSF) and to generate pinhole SPECT projection images of 2 different resolution phantoms (2.0 mm and 1.8 mm). The new Monte Carlo based PSF with edge penetration was compared to an ideal pinhole model without edge penetration. To conserve memory, the ray-driven system matrix was computed for one angle and rotation was performed by interpolating the radiotracer distribution within the object space. Detector symmetry and a bitwise incremental storage scheme were utilized for further reduction of memory requirements. Two system setups with a magnification of 7.2times and 2times were studied. Reconstruction results show an improvement in image quality and reconstruction resolution for the new pinhole PSF model. In the low magnification system operated at its resolution limits these improvements are more pronounced than in the high magnification system. The newly implemented ray-driven reconstruction method has great flexibility and offers to be a platform for further improvements such as non-uniform attenuation and scatter correction, and integration of detector misalignments in the system matrix.

Small animal imaging can provide high-throughput phenotypic data for functional genomic studies and better mechanistic understanding of disease. Fusion of anatomical and functional images will aid interpretation of functional images having relatively little anatomical detail. In this study, we are investigating automatic registration and fusion visualization methods for micro-CT and SPECT images of rat lung. The immediate application is studies of pulmonary perfusion in a healthy rat and one with an occluded left pulmonary artery. Registration experiments were performed on images acquired from rats and a phantom. Fusion visualization showed excellent registration results. Quantitative measures such as distances and perimeters from phantom results show that the registration is quite accurate.

The bronchial circulation is thought to be the primary blood supply for pulmonary carcinomas. Thus, we have developed a method for imaging and quantifying changes in perfusion in the rat lung due to development of the bronchial circulation. A dual-modality micro-CT/SPECT system was used to detect change in perfusion in two groups of rats: controls and those with a surgically occluded left pulmonary artery. Both groups were imaged following injections on separate days i) 2mCi of Tc99m labeled macroaggregated albumin (MAA) into the left carotid artery (IA) and ii) a similar injection into the femoral vein (IV). The IA injection resulted in Tc99m accumulation in capillaries of the systemic circulation including the bronchial circulation, whereas the IV resulted in Tc99m accumulation in the pulmonary capillaries. Ordered subset expectation maximization (OSEM) was used to reconstruct the SPECT image volumes and a Feldkamp algorithm was used to reconstruct the micro-CT image volumes. The micro-CT and SPECT volumes were registered, the SPECT image volume was segmented using the right and left lung boundaries defined from the micro-CT volume, and the ratio of IA radioactivity accumulation in the left lung to IV radioactivity accumulation in both lungs was used as a measure of left lung flow via the bronchial circulation. This ratio was ~0.02 for the untreated rats compared to the treated animals that had an increased flow ratio of ~0.21 40 days after left pulmonary artery occlusion. This increase in flow to the occluded left lung via the bronchial circulation suggests this will be a useful model for further investigating antiangiogenic treatments.

Small animal imaging is experiencing rapid development due to its importance in providing high-throughput phenotypic data for functional genomics studies. We have developed a single photon emission computed tomography (SPECT) system to image the pulmonary perfusion distribution in the rat. A standard gamma camera, equipped with a pinhole collimator, was used to acquire SPECT projection images at 40 sec/view of the rat thorax following injection of Tc99m labeled albumin that accumulated in the rat's lungs. A voxel-driven, ordered-subset expectation maximization reconstruction was implemented. Following SPECT imaging, the rat was imaged using micro-CT with Feldkamp conebeam reconstruction. The two reconstructed image volumes were fused to provide a structure/function image of the rat thorax. Reconstruction accuracy and performance were evaluated using numerical simulations and actual imaging of an experimental phantom consisting of Tc99m filled chambers with known diameters and count rates. Full-width half-maximum diameter measurement errors decreased with increasing chamber diameter, ranging from < 6% down to 0.1%. Errors in the ratio of count rate estimates between tubes were also diameter dependent but still relatively small. This preliminary study suggests that SPECT will be useful for imaging and quantifying the pulmonary blood flow distribution and the distribution of Tc99m labeled ligands in the lungs of small laboratory animals.

The authors applied micro-CT imaging to arterial trees in rodent lungs. Morphometric features derived from the images are sensitive to interspecies differences in vascular structure and can reflect the distensibility of arterial walls.

We evaluated the practical application of a Computer-Aided Diagnosis (CAD) system for viewing spiral computed tomography (CT) of the chest low-dose screening examinations which includes an automatic detection of pulmonary nodules. A UNIX- based CAD system was developed including a detection algorithm for pulmonary nodules and a user interface providing an original axial image, the same image with nodules highlighted, a thin-slab MIP, and a cine mode. As yet, 26 CT examinations with 1625 images were reviewed in a clinical setting and reported by an experienced radiologist using both the CAD system and hardcopies. The CT studies exhibited 19 nodules found on the hardcopies in consensus reporting of 2 experienced radiologists. Viewing with the CAD system was more time consuming than using hardcopies (4.16 vs. 2.92 min) due to analyzing MIP and cine mode. The algorithm detected 49% (18/37) pulmonary nodules larger than 5 mm and 30% (21/70) of all nodules. It produced an average of 6.3 false positive findings per CT study. Most of the missed nodules were adjacent to the pleura. However, the program detected 6 nodules missed by the radiologists. Automatic nodule detection increases the radiologists's awareness of pulmonary lesions. Simultaneous display of axial image and thin-slab MIP makes the radiologist more confident in diagnosis of smaller pulmonary nodules. The CAD system improves the detection of pulmonary nodules at spiral CT. Lack of sensitivity and specificity is still an issue to be addressed but does not prevent practical use.

Computed tomography of the chest can be used as a screening method for lung cancer in a high-risk population. However, the detection of lung nodules is a difficult and time-consuming task for radiologists. The developed technique should improve the sensitivity of the detection of lung nodules without showing too many false positive nodules. In a study, which should evaluate the feasibility of screening lung cancer, about 1400 thoracic studies were acquired. Scanning parameters were 120 kVp, 5 mm collimation pitch of 2, and a reconstruction index of 5 mm. This results in a data set of about 60 to 70 images per exam. In the images the detection technique first eliminates all air outside the patient, then soft tissue and bony structures are removed. In the remaining lung fields a three-dimensional region detection is performed and rule-based analysis is used to detect possible lung nodules. This technique was applied to a small subset (n equals 17) of above studies. Computation time is about 5 min on an O2 workstation. The use of low-dose exams proved not be a hindrance in the detection of lung nodules. All of the nodules (n equals 23), except one with a size of 3 mm, were detected. The false positive rate was less than 0.3 per image. We have developed a technique, which might help the radiologist in the detection of pulmonary nodules in CT exams of the chest.© (1999) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Detection of breast cancer by positron emission tomography (PET) imaging with 2-(fluorine-18)-2-deoxy-D-glucose (FDG) as the tracer molecule is limited in part by both tumor dimension and metabolic activity. While some types of aggressive breast cancers are associated with a high capacity for FDG uptake, more indolent breast cancers are characterized by low FDG uptake. Moreover, detection of malignant lesions in most clinical settings requires tumor dimensions ≥ 10 mm. Development of a method to increase the fractional uptake of FDG by cancer tissue would provide a means to detect smaller tumors. However, there is no clinically available pharmacologic reagent known to enhance the preferential uptake of FDG by cancer tissue. Because the vanadyl (VO2+) chelate bis(acetylacetonato)oxovanadium(IV) [VO(acac)2] is known to enhance cellular uptake of glucose, we have investigated whether VO(acac)2 facilitates enhanced uptake of FDG by cultured human breast carcinoma cells. We observed that the fractional uptake of FDG by cultured human MDA-MB-231 carcinoma cells is increased in the presence of VO(acac)2 in a dose dependent manner. Preliminary results with xenograft tumors generated in severely compromised, immunodeficient (SCID) female mice showed that VO(acac)2 treatment of mice 3 – 4 hr prior to FDG injection enhanced FDG uptake by the malignant tissue by a factor > 2.0 compared with that by normal surrounding tissue.

Purpose: To study the feasibility of using 2‐Deoxy‐D‐Glucose (2‐DG) labeled gold nanoparticle (AuNP‐DG) as a metabolic functional CTcontrast agent through in vitro experiments. Method and Materials: The goldnanoparticles (AuNP) were fabricated using a citrate acid reduction method. The size of the AuNP was determined from Transmission Electron Microscopy images to be 4 nm in diameter. The conjugation of the 2‐DG with the AuNP core was accomplished using mercapto group in the 2‐carbon position by condensation reaction of 2‐amino‐deoxyglucose with mercaptosuccinic acid. The human alveolar epithelial cancer cell line, A‐549, was chosen for the in vitro cellular uptake assay. Two groups of cell samples (∼1 × 105 cells per sample) were incubated with the AuNP‐DG and the unlabeled AuNP, respectively, for 30 minutes (37°C, 7% CO2). Following the incubation, the cells were washed with sterile PBS six times to remove the excess goldnanoparticles. The cells were then spun to cell pellets using a centrifuge. The cell pellets were imaged using a microCT scanner immediately after the centrifuging (75 kVp, 135 μA, 1184 × 1120 matrix size, 360 views, averaging 5 frames per view). The reconstructedCTimages were analyzed using a commercial software package. Results: Significant contrast enhancement in the cell samples incubated with the AuNP‐DG with respect to the cell samples incubated with the unlabeled AuNP was observed in multiple CT slices. Quantitative analysis of the image data showed that (45.6 ± 14.2)% of the cells that were incubated with the AuNP‐DG exhibit enhanced contrast compared to the cells in the control group (incubated with AuNP). Conclusion: Results from these experiments strongly suggest enhanced uptake of the AuNP‐DG over the unlabeled AuNP by the highly glycolytic cancer cells in vitro and indicate that AuNP‐DG could served as a metabolic functional CTcontrast agent with tumor‐specific targeting capability.