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      1. Author :
        Las Heras, F.; DaCosta, R. S.; Pritzker, K. P.; Haroon, N.; Netchev, G.; Tsui, H. W.; Chiu, B.; Erwin, W. M.; Tsui, F. W.; Inman, R. D.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Arthritis Res Ther
      6. Products :
      7. Volume :
        13
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        OsteoSense, Animals; Axis/chemistry/*metabolism/*pathology; *Calcification, Physiologic/genetics; Inflammation/genetics/metabolism/prevention & control; Mice; Mice, Transgenic; Molecular Imaging/*methods; Spondylitis, Ankylosing/diagnosis/*genetics/*metabolism; Time Factors
      12. Abstract :
        INTRODUCTION: The diagnosis of ankylosing spondylitis is made from a combination of clinical features and the presence of radiographic evidence that may be detected only after many years of inflammatory back pain. It is not uncommon to have a diagnosis confirmed 5 to 10 years after the initial onset of symptoms. Development of a more-sensitive molecular imaging technology to detect structural changes in the joints would lead to earlier diagnosis and quantitative tracking of ankylosis progression. Progressive ankylosis (ank/ank) mice have a loss of function in the Ank gene, which codes for a regulator of PPi transport. In this study, we used these ank/ank mutant mice to assess a noninvasive, quantitative measure of joint ankylosis with near-infrared (NIR) molecular imaging in vivo. METHODS: Three age groups (8, 12, and 18 weeks) of ank/ank (15 mice) and wild-type littermates (12 +/+ mice) were assessed histologically and radiographically. Before imaging, OsteoSense 750 (bisphosphonate pamidronate) was injected i.v. Whole-body images were analyzed by using the multispectral Maestro imaging system. RESULTS: OsteoSense 750 signals in the paw joints were higher in ank/ank mice in all three age groups compared with controls. In the spine, significantly higher OsteoSense 750 signals were detected early, in 8-week-old ank/ank mice compared with controls, although minimal radiographic differences were noted at this time point. The molecular imaging changes in the ank/ank spine (8 weeks) were supported by histologic changes, including calcium apatite crystals at the edge of the vertebral bodies and new syndesmophyte formation. CONCLUSIONS: Changes in joint pathology of ank/ank mice, as evaluated by histologic and radiographic means, are qualitative, but only semiquantitative. In contrast, molecular imaging provides a quantitative assessment. Ankylosis in ank/ank mice developed simultaneously in distal and axial joints, contrary to the previous notion that it is a centripetal process. NIR imaging might be feasible for early disease diagnosis and for monitoring disease progression in ankylosing spondylitis.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21992149
      14. Call Number :
        PKI @ kd.modi @ 3
      15. Serial :
        10471
      1. Author :
        Nakayama, H.; Kawase, T.; Okuda, K.; Wolff, L. F.; Yoshie, H.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Acta Radiol
      6. Products :
      7. Volume :
        52
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        OsteoSense,, Animals; Bone Neoplasms/*pathology/physiopathology; Calcification, Physiologic/*physiology; Diphosphonates/diagnostic use; Feasibility Studies; Inositol/analogs & derivatives/diagnostic use; Mice; Mice, Hairless; Osteosarcoma/*pathology/physiopathology; Radiopharmaceuticals/diagnostic use; Spectroscopy, Near-Infrared/*methods; Technetium Tc 99m Medronate/analogs & derivatives/diagnostic use; Transplantation, Heterologous
      12. Abstract :
        BACKGROUND: In a previous study using a rodent osteosarcoma-grafted rat model, in which cell-dependent mineralization was previously demonstrated to proportionally increase with growth, we performed a quantitative analysis of mineral deposit formation using (99m)Tc-HMDP and found some weaknesses, such as longer acquisition time and narrower dynamic ranges (i.e. images easily saturated). The recently developed near-infrared (NIR) optical imaging technique is expected to non-invasively evaluate changes in living small animals in a quantitative manner. PURPOSE: To test the feasibility of NIR imaging with a dual-channel system as a better alternative for bone scintigraphy by quantitatively evaluating mineralization along with the growth of osteosarcoma lesions in a mouse-xenograft model. MATERIAL AND METHODS: The gross volume and mineralization of osteosarcoma lesions were evaluated in living mice simultaneously with dual-channels by NIR dye-labeled probes, 2-deoxyglucose (DG) and pamidronate (OS), respectively. To verify these quantitative data, retrieved osteosarcoma lesions were then subjected to ex-vivo imaging, weighing under wet conditions, microfocus-computed tomography (muCT) analysis, and histopathological examination. RESULTS: Because of less scattering and no anatomical overlapping, as generally shown, specific fluorescence signals targeted to the osteosarcoma lesions could be determined clearly by ex-vivo imaging. These data were well positively correlated with the in-vivo imaging data (r > 0.8, P < 0.02). Other good to excellent correlations (r > 0.8, P < 0.02) were observed between DG accumulation and tumor gross volume and between OS accumulation and mineralization volume. CONCLUSION: This in-vivo NIR imaging technique using DG and OS is sensitive to the level to simultaneously detect and quantitatively evaluate the growth and mineralization occuring in this type of osteosarcoma lesions of living mice without either invasion or sacrifice. By possible mutual complementation, this dual imaging system might be useful for accurate diagnosis even in the presence of overlapping tissues.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21969703
      14. Call Number :
        PKI @ kd.modi @ 7
      15. Serial :
        10472
      1. Author :
        Penna, F. J.; Chow, J. S.; Minnillo, B. J.; Passerotti, C. C.; Barnewolt, C. E.; Treves, S. T.; Fahey, F. H.; Dunning, P. S.; Freilich, D. A.; Retik, A. B.; Nguyen, H. T.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        J Urol
      6. Products :
      7. Volume :
        185
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        OsteoSense, Animals; Diagnostic Imaging; Disease Models, Animal; Fluorescence; *Kidney Pelvis; Mice; Ureteral Obstruction/*diagnosis
      12. Abstract :
        PURPOSE: Radiological imaging is the mainstay of diagnosing ureteropelvic junction obstruction. Current established radiological modalities can potentially differentiate the varying degrees of obstruction but they are limited in functionality, applicability and/or comprehensiveness. Of particular concern is that some tests require radiation, which has long-term consequences, especially in children. MATERIALS AND METHODS: We investigated the novel use of Genhance 680 dynamic fluorescence imaging to assess ureteropelvic junction obstruction in 20 mice that underwent partial or complete unilateral ureteral obstruction. Ultrasound, mercaptoacetyltriglycine renography, magnetic resonance imaging and fluorescence imaging were performed. RESULTS: Our model of partial and complete obstruction could be distinguished by ultrasound, mercaptoacetyltriglycine renography and magnetic resonance imaging, and was confirmed by histological analysis. Using fluorescence imaging distinct vascular and urinary parameters were identified in the partial and complete obstruction groups compared to controls. CONCLUSIONS: Fluorescence imaging is a feasible alternative radiological imaging modality to diagnose ureteropelvic junction obstruction. It provides continuous, detailed imaging without the risk of radiation exposure.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21511294
      14. Call Number :
        PKI @ kd.modi @ 14
      15. Serial :
        10473
      1. Author :
        Penna, F. J.; Freilich, D. A.; Alvarenga, C.; Nguyen, H. T.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Urology
      6. Products :
      7. Volume :
        78
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        OsteoSense, Animals; Fluorescence; Fluorescent Dyes/*diagnostic use; Guinea Pigs; Lymph Node Excision/*methods; Male; Models, Animal; *Molecular Imaging; Retroperitoneal Space
      12. Abstract :
        OBJECTIVES: To propose that fluorescent molecular imaging has utility in specifically identifying the lymph nodes, thereby enabling more definitive lymph node visualization and dissection. Retroperitoneal lymph node dissection (RPLND) is an invasive procedure with significant morbidity. A minimally invasive approach would be of great clinical benefit but has been limited by the extensive perivascular dissection required to remove all lymphatic tissue. Directed lymph node visualization would allow a limited dissection, making a laparoscopic approach more feasible. METHODS: Ten male Hartley guinea pigs underwent nonsurvival RPLND, 5 with the protease activatable in vivo fluorescent molecular imaging agent, ProSense and 5 without image guidance (control). ProSense was administered 24 hours before surgery and detected 24 hours later using a photodynamic detector. In group 1, RPLND was first performed without molecular imaging followed by image-guided lymph node dissection for residual nodes. In group 2, the near infrared detector was used initially for lymph node excision followed by traditionally unassisted extraction of the residual lymph nodes. The lymph nodes were extracted, counted, and sent for histopathologic analysis. RESULTS: With the assistance of molecular imaging, no additional lymph nodes were identified after complete dissection, and all tissue identified by ProSense was confirmed by histopathologic analysis to be lymph nodes. Without molecular imaging, all lymph nodes were not identified, and in 2 instances, the tissue was incorrectly thought to be lymphatic tissue. CONCLUSIONS: Molecular image-guided RPLND is a promising technique to improve in vivo, live visualization and dissection of lymph nodes and has the potential for application in improving the diagnosis and treatment of other urologic malignancies.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21601249
      14. Call Number :
        PKI @ kd.modi @ 13
      15. Serial :
        10474
      1. Author :
        Sabbagh, Y.; Graciolli, F. G.; O'Brien, S.; Tang, W.; dos Reis, L. M.; Ryan, S.; Phillips, L.; Boulanger, J.; Song, W.; Bracken, C.; Liu, S.; Ledbetter, S.; Dechow, P.; Canziani, M. E.; Carvalho, A. B.; Jorgetti, V.; Moyses, R. M.; Schiavi, S. C.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        J Bone Miner Res
      6. Products :
      7. Volume :
        27
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        OsteoSense, Animals; Biopsy; Bone Remodeling; Bone and Bones/metabolism/pathology; Calcification, Physiologic; Cardiovascular Abnormalities/blood/complications/pathology/physiopathology; *Disease Progression; Female; Gene Expression Profiling; Gene Expression Regulation; Glycoproteins/metabolism; Humans; Kidney Failure, Chronic/blood/complications/pathology/physiopathology; Male; Mice; Mice, Inbred C57BL; Middle Aged; Mutation/genetics; Osteoclasts/metabolism/pathology; Osteocytes/*metabolism/*pathology; Protein-Serine-Threonine Kinases/genetics; Renal Osteodystrophy/blood/*metabolism/*pathology/physiopathology; Vascular Calcification; *Wnt Signaling Pathway/genetics
      12. Abstract :
        Chronic kidney disease-mineral bone disorder (CKD-MBD) is defined by abnormalities in mineral and hormone metabolism, bone histomorphometric changes, and/or the presence of soft-tissue calcification. Emerging evidence suggests that features of CKD-MBD may occur early in disease progression and are associated with changes in osteocyte function. To identify early changes in bone, we utilized the jck mouse, a genetic model of polycystic kidney disease that exhibits progressive renal disease. At 6 weeks of age, jck mice have normal renal function and no evidence of bone disease but exhibit continual decline in renal function and death by 20 weeks of age, when approximately 40% to 60% of them have vascular calcification. Temporal changes in serum parameters were identified in jck relative to wild-type mice from 6 through 18 weeks of age and were subsequently shown to largely mirror serum changes commonly associated with clinical CKD-MBD. Bone histomorphometry revealed progressive changes associated with increased osteoclast activity and elevated bone formation relative to wild-type mice. To capture the early molecular and cellular events in the progression of CKD-MBD we examined cell-specific pathways associated with bone remodeling at the protein and/or gene expression level. Importantly, a steady increase in the number of cells expressing phosphor-Ser33/37-beta-catenin was observed both in mouse and human bones. Overall repression of Wnt/beta-catenin signaling within osteocytes occurred in conjunction with increased expression of Wnt antagonists (SOST and sFRP4) and genes associated with osteoclast activity, including receptor activator of NF-kappaB ligand (RANKL). The resulting increase in the RANKL/osteoprotegerin (OPG) ratio correlated with increased osteoclast activity. In late-stage disease, an apparent repression of genes associated with osteoblast function was observed. These data confirm that jck mice develop progressive biochemical changes in CKD-MBD and suggest that repression of the Wnt/beta-catenin pathway is involved in the pathogenesis of renal osteodystrophy.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22492547
      14. Call Number :
        PKI @ kd.modi @ 10
      15. Serial :
        10475
      1. Author :
        Snoeks, T. J.; Khmelinskii, A.; Lelieveldt, B. P.; Kaijzel, E. L.; Lowik, C. W.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Bone
      6. Products :
      7. Volume :
        48
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        OsteoSense, Animals; Bone Neoplasms/radionuclide imaging/*secondary; Diagnostic Imaging/*methods; Forecasting; Optics and Photonics/*trends; Positron-Emission Tomography/methods; Tomography, Emission-Computed, Single-Photon/methods; X-Ray Microtomography/methods; X-Rays
      12. Abstract :
        Optical Imaging has evolved into one of the standard molecular imaging modalities used in pre-clinical cancer research. Bone research however, strongly depends on other imaging modalities such as SPECT, PET, x-ray and muCT. Each imaging modality has its own specific strengths and weaknesses concerning spatial resolution, sensitivity and the possibility to quantify the signal. An increasing number of bone specific optical imaging models and probes have been developed over the past years. This review gives an overview of optical imaging modalities, models and probes that can be used to study skeletal complications of cancer in small laboratory animals.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20688203
      14. Call Number :
        PKI @ kd.modi @ 6
      15. Serial :
        10476
      1. Author :
        Tremoleda, J. L.; Khalil, M.; Gompels, L. L.; Wylezinska-Arridge, M.; Vincent, T.; Gsell, W.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        EJNMMI Res
      6. Products :
      7. Volume :
        1
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        OsteoSense
      12. Abstract :
        Preclinical models for musculoskeletal disorders are critical for understanding the pathogenesis of bone and joint disorders in humans and the development of effective therapies. The assessment of these models primarily relies on morphological analysis which remains time consuming and costly, requiring large numbers of animals to be tested through different stages of the disease. The implementation of preclinical imaging represents a keystone in the refinement of animal models allowing longitudinal studies and enabling a powerful, non-invasive and clinically translatable way for monitoring disease progression in real time. Our aim is to highlight examples that demonstrate the advantages and limitations of different imaging modalities including magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), single-photon emission computed tomography (SPECT) and optical imaging. All of which are in current use in preclinical skeletal research. MRI can provide high resolution of soft tissue structures, but imaging requires comparatively long acquisition times; hence, animals require long-term anaesthesia. CT is extensively used in bone and joint disorders providing excellent spatial resolution and good contrast for bone imaging. Despite its excellent structural assessment of mineralized structures, CT does not provide in vivo functional information of ongoing biological processes. Nuclear medicine is a very promising tool for investigating functional and molecular processes in vivo with new tracers becoming available as biomarkers. The combined use of imaging modalities also holds significant potential for the assessment of disease pathogenesis in animal models of musculoskeletal disorders, minimising the use of conventional invasive methods and animal redundancy.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22214535
      14. Call Number :
        PKI @ kd.modi @ 15
      15. Serial :
        10477
      1. Author :
        van der Horst, G.; van der Pluijm, G.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Future Oncol
      6. Products :
      7. Volume :
        8
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        OsteoSense, Animals; Bone Neoplasms/*diagnosis/*secondary; Diagnostic Imaging/*methods; Disease Models, Animal; Disease Progression; Humans; Molecular Imaging/methods; Neoplasm Metastasis/diagnosis
      12. Abstract :
        Bone metastasis is a complex process that ultimately leads to devastating metastatic bone disease. It is therefore of key interest to unravel the mechanisms underlying the multistep process of skeletal metastasis and cancer-induced bone disease, and to develop better treatment and management of patients with this devastating disease. Fortunately, novel technologies are rapidly emerging that allow real-time imaging of molecules, pathogenic processes, drug delivery and drug response in preclinical in vivo models. The outcome of these experimental studies will facilitate clinical cancer research by improving the detection of cancer cell invasion, metastasis and therapy response.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22515445
      14. Call Number :
        PKI @ kd.modi @ 16
      15. Serial :
        10478
      1. Author :
        Pribaz, J. R.; Bernthal, N. M.; Billi, F.; Cho, J. S.; Ramos, R. I.; Guo, Y.; Cheung, A. L.; Francis, K. P.; Miller, L. S.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Journal of orthopaedic research : official publication of the Orthopaedic Research Society
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        N/A
      12. Abstract :
        Post-arthroplasty infections are a devastating problem in orthopaedic surgery. While acute infections can be treated with a single stage washout and liner exchange, chronic infections lead to multiple reoperations, prolonged antibiotic courses, extended disability, and worse clinical outcomes. Unlike previous mouse models that studied an acute infection, this work aimed to develop a model of a chronic post-arthroplasty infection. To achieve this, a stainless steel implant in the knee joints of mice was inoculated with a bioluminescent Staphylococcus aureus strain (1 x 10(2) -1 x 10(4) colony forming units, CFUs) and in vivo imaging was used to monitor the bacterial burden for 42 days. Four different S. aureus strains were compared in which the bioluminescent construct was integrated in an antibiotic selection plasmid (ALC2906), the bacterial chromosome (Xen29 and Xen40), or a stable plasmid (Xen36). ALC2906 had increased bioluminescent signals through day 10, after which the signals became undetectable. In contrast, Xen29, Xen40, and Xen36 had increased bioluminescent signals through 42 days with the highest signals observed with Xen36. ALC2906, Xen29, and Xen40 induced significantly more inflammation than Xen36 as measured by in vivo enhanced green fluorescence protein (EGFP)-neutrophil flourescence of LysEGFP mice. All four strains induced comparable biofilm formation as determined by variable-pressure scanning electron microscopy. Using a titanium implant, Xen36 had higher in vivo bioluminescence signals than Xen40 but had similar biofilm formation and adherent bacteria. In conclusion, Xen29, Xen40, and especially Xen36, which had stable bioluminescent constructs, are feasible for long-term in vivo monitoring of bacterial burden and biofilm formation to study chronic post-arthroplasty infections and potential antimicrobial interventions. (c) 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21837686
      14. Call Number :
        142237
      15. Serial :
        6983
      1. Author :
        Liao, A. H.; Li, Y. K.; Lee, W. J.; Wu, M. F.; Liu, H. L.; Kuo, M. L.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Ultrasound Med Biol
      6. Products :
      7. Volume :
        38
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        4T1-luc2, IVIS, Bioluminescence
      12. Abstract :
        The application of drug-loaded microbubbles (MBs) in combination with ultrasound (US), which results in an increase in capillary permeability at the site of US-sonication-induced MB destruction, may be an efficient method of localized drug delivery. This study investigated the mechanism underlying the US-mediated release of luciferin-loaded MBs through the blood vessels to targeted cells using an in vivo bioluminescence imaging (BLI) system. The luciferin-loaded MBs comprised an albumin shell with a diameter of 1234 +/- 394 nm (mean +/- SD) and contained 2.48 x 10(9) bubbles/mL; within each MB, the concentration of encapsulated luciferin was 1.48 x 10(-)(1)(0) mg/bubble. The loading efficiency of luciferin in MBs was only about 19.8%, while maintaining both the bioluminescence and acoustic properties. In vitro and in vivo BLI experiments were performed to evaluate the US-mediated release of luciferin-loaded MBs. For in vitro results, the increase in light emission of luciferin-loaded albumin-shelled MBs after destruction via US sonication (6.24 +/- 0.72 x 10(7) photons/s) was significantly higher than that in the luciferin-loaded albumin-shelled MBs (3.11 +/- 0.33 x 10(7) photons/s) (p < 0.05). The efficiency of the US-mediated release of luciferin-loaded MBs in 4T1-luc2 tumor-bearing mice was also estimated. The signal intensity of the tumor with US destruction at 3 W/cm(2) for 30 s was significantly higher than without US destruction at 3 (p = 0.025), 5 (p = 0.013), 7 (p = 0.012) and 10 (p = 0.032) min after injecting luciferin-loaded albumin-shelled MBs. The delivery efficiency was, thus, improved with US-mediated release, allowing reduction of the total injection dose of luciferin.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22929655
      14. Call Number :
        PKI @ kd.modi @ 8
      15. Serial :
        10481