MRI and image quantitation for drug assessment - Growth effects of anabolic steroids and precursors

MRI and image quantitation play an expanding role in modern drug research, because MRI offers high resolution and non-invasive ability, and provides excellent soft tissue contrast. Moreover, with development of effective image segmentation and analysis methods, in-vivo and serial tissue growth measurements could be assessed. In the study, MR image acquisition and analysis protocol were established and validated for investigating the effects of anabolic steroids and precursors on muscle growth and body composition in a guinea pig model. Semi-automatic and interactive segmentation methods were developed to accurately label the tissue of interest for tissue volume estimation. In addition, a longitudinal tissue area outlining procedure was proposed for study of tissue geometric features in relation to tissue growth. Finally, a fully automatic data retrieval and analysis scheme was implemented to facilitate the overall huge amount of image quantitation, statistical analysis, as well as study group comparisons. As a result, highly significant differences in muscle and organ growth were detected between intact and castrated guinea pigs using the selected anabolic steroids, indicating the viability of employing such protocol to assess other anabolic steroids. Furthermore, the anabolic potential of selected steroid precursors and their effects on muscle growth, in comparison with that in respective positive control groups of castrated guinea pigs, were evaluated with the proposed protocol. © 2005 IEEE.published_or_final_versio

Gradient reversal technique revisited for simultaneous water and fat imaging at high field

Qualitative and quantitative MR imaging of water and fat is of great importance in obesity and diabetic research, osteoarthritis cartilage visualization, body composition measurement, and drug evaluation studies. In this study, we revisited the gradient reversal technique, along with a chemical-shift-specific sliceselection (C4S) method. Simultaneous water and fat imaging approach was implemented at 11.7T. Using this technique, high quality water and fat images at the identical slice locations with in-plane chemical-shift correction were acquired in a single acquisition without increase in acquisition time. Applications in in vivo quantitative tissue lipid imaging were demonstrated.published_or_final_versio

MRI and image quantitation for assessment of the growth effects of anabolic steroid precursors in a guinea pig model

MRI and image quantitation play an expanding role in modern drug research. With effective image segmentation and analysis methods, in vivo and longitudinal tissue growth can be assessed. The effects of the nandrolone and testosterone steroids on muscle growth have been investigated previously, in which MRI acquisition and analysis protocol were established, and excellent correlations were found between MRI measurement and dissection analyzes. In this study, the MRI protocol was used to evaluate the anabolic potential of 4 steroid precursors. The effects on muscle growth in castrated guinea pigs, in comparison with that of respective positive control steroids were determined.MRI and image quantitation play an expanding role in modern drug research. With effective image segmentation and analysis methods, in vivo and longitudinal tissue growth can be assessed. The effects of the nandrolone and testosterone steroids on muscle growth have been investigated previously, in which MRI acquisition and analysis protocol were established, and excellent correlations were found between MRI measurement and dissection analyzes. In this study, the MRI protocol was used to evaluate the anabolic potential of 4 steroid precursors. The effects on muscle growth in castrated guinea pigs, in comparison with that of respective positive control steroids were determined.published_or_final_versio

Single-breathhold myocardial T2 and T2* quantification in normal volunteer subjects at 3T

Myocardial Tissue Characterization: Fat, Hemorrhage & Edema - Poster presentationIncreased B0 and B1 inhomogeneity, together with increased motion artifacts, present challenges for cardiac imaging and quantitation at 3T. This study measured myocardial T2 in normal subjects at 3T using a novel single-breathhold black-blood hybrid TSE/MESE T2 measurement protocol. The average myocardial T2 was found to be 39.6±7.4ms, with peak-to-peak variations of the measured T2 values < 5%. The results demonstrate the feasibility of myocardial T2 quantitation at 3T.published_or_final_versionThe 17th Scientific Meeting & Exhibition of the International Society of Magnetic Resonance in Medicine (ISMRM), Honolulu, HI., 18-24 April 2009. In Proceedings of ISMRM 17th Scientific Meeting & Exhibition, 2009, p. 375

Non-viral Smad7 gene delivery and attenuation of postoperative peritoneal adhesion in an experimental model

Background: Postoperative intra-abdominal adhesion is associated with high morbidity and mortality. Smad7, a protein that occupies a strategic position in fibrogenesis, inhibits the transforming growth factor (TGF) β/Smad signalling pathway. In this study the therapeutic potential of exogenous Smad7 in preventing fibrogenesis in postoperative intra-abdominal adhesion was investigated. Methods: Intra-abdominal adhesion was induced in a rodent model by peritoneal abrasion. Smad7 was delivered into the peritoneal cavity by a non-viral ultrasound-microbubble-mediated naked gene transfection system. The effect of Smad7 transgene on adhesion formation was studied by measuring changes in TGF-β, fibrogenic factors, α-SMA and Smad2/3 activation in the anterior abdominal wall. Results: Four weeks after surgical abrasion, all rats developed significant peritoneal adhesion with enhanced TGF-β expression, increased levels of extracellular matrix components and activated myofibroblasts, accompanied by decreased Smad7 expression and increased Smad2/3 activation. In rats treated with the Smad7 transgene, the incidence and severity of peritoneal adhesion were significantly reduced, with biochemical downregulation of fibrogenic factors and inhibition of Smad2/3 activation. Serial quantitation using magnetic resonance imaging revealed a significant reduction in adhesion areas from day 14 onwards. Conclusion: Ultrasound-microbubble-mediated gene transfection provides timely targeted gene delivery for the treatment of postoperative peritoneal adhesions. Copyright © 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons Ltd.postprin

Automated adaptive analysis of tagged magnetic resonance images of the mouse heart

The full potential of tagged MRI of the mouse heart for non-invasive evaluation of cardiac mechanics in transgenic animals has not been realized due to excessive user involvement with available image processing algorithms. Therefore, we developed an automated, rapid, high-resolution analysis technique, called High Density Mapping (HDM), that uses spectral correlation to efficiently quantify regional wall deformation, does not entail tracking of individual tags, and involves minimal user interaction. HDM analysis distinguishes regional mechanics in healthy and infarcted mice within 2 minutes. This new method may help promote the practical use of tagged MRI in mice and other species.published_or_final_versio

Gas-filled microbubbles as intravascular R(2)* contrast agent for liver MRI

Session 73: Contrast Agents & Microvascular Function: Methods - Oral presentationGas-filled microbubbles possess the potential to become a unique MR contrast agent because of their magnetic susceptibility effect, high biocompatibility and unique cavitation and sonoporation properties. In this study, microbubble susceptibility induced changes were investigated using custom-made albumin-coated microbubbles and a commercially available lipid-based clinical ultrasound contrast agent SonoVue® in rat livers in vivo with dynamic susceptibility weighted MRI at 7T. The results demonstrate the potential of gas-filled microbubble as an intravascular R(2)* contrast agent for liver MRI at high field.published_or_final_versionThe 17th Scientific Meeting & Exhibition of the International Society of Magnetic Resonance in Medicine (ISMRM), Honolulu, HI., 18-24 April 2009. In Proceedings of ISMRM 17th Scientific Meeting & Exhibition, 2009, p. 72

MRI detection of peritoneal adhesion with dialysate enhancement

This study investigated the use of clinical peritoneal dialysis fluid (dialysate) as a peritoneal contrast agent to visualize peritoneal adhesions in rats at 7 Tesla. Intraperitoneal injection of dialysate (~0.1 mL/g) allowed the MR detection of peritoneal adhesions that were surgically induced in all rats studied (N = 6). MR measurements of adhesion surface areas correlated well with the postmortem estimations (R = 0.99). T1 and T2 values of undiluted dialysate were found to be 3017.5¡Ó35.3 ms and 108.4¡Ó2.0 ms, respectively. These findings demonstrated dialysate-enhanced MRI as a potentially valuable technique in clinical detection and evaluation of post-surgical peritoneal adhesion and to monitor therapeutic interventions (i.e., against peritoneal adhesion) in future preclinical research.published_or_final_versio

Myocardial fiber length mapping with MR diffusion tensor imaging

Diffusion tensor MRI is emerging as a rapid, nondestructive method to map myocardial fiber organization. A precise biological description of myocardial fiber performance requires knowledge of four variables: length, force, velocity and time. However, study of quantification of myocardial fiber length is lacking. The current study aims to show myocardial fiber length maps of formalin-fixed heats. Diffusion tensor MRI with medium diffusion resolution (15 directions) was performed in one isolated pig heart. Fiber length maps were investigated in multiple short-axis slices. The results provide supplementary information of myocardial fiber organization. To our knowledge, the present study is the first report of the myocardial fiber length mapping. © 2005 IEEE.published_or_final_versio

Axial and radial diffusivities as potential markers for characterization of white matter lesions and predicting lesion outcome in a neonatal rat hypoxia-ischemia model

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