The Development of Non-Radiative Probes for In Vivo Applications

Author(s):  
Andrew Tsourkas ◽  
Lee Josephson ◽  
Ralph Weissleder

Recently, the field of activatable probes has been extended from fluorescence to magnetic resonance (MR). Magnetic relaxation switches take advantage of the change in T2 relaxation time that occurs upon binding of multiple bioconjugated superparamagnetic iron-oxide nanoparticles to a target. Here, we use a model system to detect biotinilated BSA using switchable magnetic particles. The presence of the biotinilated BSA results in the aggregation of nanoparticles and leas to a substantial decrease in the T2 relaxation time. Magnetic relaxation switches show great promise for clinical in vitro diagnostics and in vivo imaging since changes in T2 are independent of the sample medium. Tests can be performed in turbid solutions without loss of sensitivity, unlike with fluorescence measurements.

2020 ◽  
Author(s):  
Dokwan Lee ◽  
Ki-Taek Hong ◽  
Tae Seong Lim ◽  
Eugene Lee ◽  
Ye Hyun Lee ◽  
...  

Abstract Background: The role of altered joint mechanics on cartilage degeneration in in vivo models has not been studied successfully due to a lack of pre-injury information. We aimed 1) to develop an accurate in vivo canine model to measure the changes in joint loading and T2 star (T2*) relaxation time before and after unilateral supraspinatus tendon resections, and 2) to find the relationship between regional variations in articular cartilage loading patterns and T2* relaxation time distributions.Methods: Rigid markers were implanted in the scapula and humerus of tested dogs. The movement of the shoulder bones were measured by a motion tracking system during normal gaits. In vivo cartilage contact strain was measured by aligning 3D shoulder models with the motion tracking data. Articular cartilage T2* relaxation times were measured by quantitative MRI scans. Articular cartilage contact strain and T2* relaxation time were compared in the shoulders before and three months after the supraspinatus tendon resections.Results: Excellent accuracy and reproducibility were found in our in vivo contact strain measurements with less than 1% errors. Changes in articular cartilage contact strain exhibited similar patterns with the changes in the T2* relaxation time after resection surgeries. Regional changes in the articular cartilage T2* relaxation time exhibited positive correlations with regional contact strain variations three months after the supraspinatus resection surgeries.Conclusion: This is the first study to measure in vivo articular cartilage contact strains with high accuracy and reproducibility. Positive correlations between contact strain and T2* relaxation time suggest that the articular cartilage extracellular matrix may responds to mechanical changes in local areas.


2007 ◽  
Vol 7 (5) ◽  
pp. 150S
Author(s):  
Paul Anderson ◽  
Victor Haughton ◽  
Donna Blankenbaker ◽  
Nick Marinelli

Author(s):  
Isaac D. Chappell ◽  
Phil Lee ◽  
Terence E. McIff ◽  
E. Bruce Toby ◽  
Kenneth J. Fischer

Osteoarthritis (OA) is a serious and frequently occuring outcome of untreated scapholunate dissocation, the most common form of carpal instability in the wrist [1]. As cartilage degenerates, the water content of surrounding tissue becomes less bound. Magnetic resonance imaging (MRI) T2 relaxation time is longer when water content is less bound [2]. MRI offers the advantageous combination of detailed images of soft tissues such as cartilage with the ability to evaluate free water content. Contrasting the various T2 relaxation times found in the cartilage of healthy wrist surfaces with those of injured wrists is thereby proposed as a method of evaluating cartilage degeneration. We hypothesized that T2 values obtained would be longer for the cartilage of the injured wrists. Though surgical treatment may relieve pain and restore some function to the wrist, it is hypothesized that T2 relaxation time will remain increased after surgery as cartilage regeneration is a very slow process, if it happens at all. The goal of this research is to provide a method to evaluate the biochemical and infer the biomechanical integrity of cartilage for various cartilage surfaces in a wrist after injury.


2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Fei Yan ◽  
Wei Yang ◽  
Xiang Li ◽  
Hongmei Liu ◽  
Xiang Nan ◽  
...  

The goal of this study is to investigate the feasibility of using CD81- (Cluster of Differentiation 81 protein-) targeted microparticles of iron oxide (CD81-MPIO) for magnetic resonance imaging (MRI) of the murine atherosclerosis. CD81-MPIO and IgG- (Immunoglobulin G-) MPIO were prepared by covalently conjugating, respectively, with anti-CD81 monoclonal and IgG antibodies to the surface of the tosyl activated MPIO. The relevant binding capability of the MPIO was examined by incubating them with murine bEnd.3 cells stimulated with phenazine methosulfate (PMS) and its effect in shortening T2 relaxation time was also examined. MRI in apolipoprotein E-deficient mice was studied in vivo. Our results show that CD81-MPIO, but not IgG-MPIO, can bind to the PMS-stimulated bEnd.3 cells. The T2 relaxation time was significantly shortened for stimulated bEnd.3 cells when compared with IgG-MPIO. In vivo MRI in apolipoprotein E-deficient mice showed highly conspicuous areas of low signal after CD81-MPIO injection. Quantitative analysis of the area of CD81-MPIO contrast effects showed 8.96- and 6.98-fold increase in comparison with IgG-MPIO or plain MPIO, respectively (P<0.01). Histological assay confirmed the expression of CD81 and CD81-MPIO binding onto atherosclerotic lesions. In conclusion, CD81-MPIO allows molecular assessment of murine atherosclerotic lesions by magnetic resonance imaging.


1997 ◽  
Vol 15 (10) ◽  
pp. 1177-1186 ◽  
Author(s):  
Gary P. Liney ◽  
Lindsay W. Turnbull ◽  
Martin Lowry ◽  
Lesley S. Turnbull ◽  
Adrian J. Knowles ◽  
...  

Polymers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 3825
Author(s):  
Mauro Petretta ◽  
Alessandro Gambardella ◽  
Giovanna Desando ◽  
Carola Cavallo ◽  
Isabella Bartolotti ◽  
...  

Multifunctional and resistant 3D structures represent a great promise and a great challenge in bone tissue engineering. This study addresses this problem by employing polycaprolactone (PCL)-based scaffolds added with hydroxyapatite (HAp) and superparamagnetic iron oxide nanoparticles (SPION), able to drive on demand the necessary cells and other bioagents for a high healing efficiency. PCL-HAp-SPION scaffolds with different concentrations of the superparamagnetic component were developed through the 3D-printing technology and the specific topographical features were detected by Atomic Force and Magnetic Force Microscopy (AFM-MFM). AFM-MFM measurements confirmed a homogenous distribution of HAp and SPION throughout the surface. The magnetically assisted seeding of cells in the scaffold resulted most efficient for the 1% SPION concentration, providing good cell entrapment and adhesion rates. Mesenchymal Stromal Cells (MSCs) seeded onto PCL-HAp-1% SPION showed a good cell proliferation and intrinsic osteogenic potential, indicating no toxic effects of the employed scaffold materials. The performed characterizations and the collected set of data point on the inherent osteogenic potential of the newly developed PCL-HAp-1% SPION scaffolds, endorsing them towards next steps of in vitro and in vivo studies and validations.


2020 ◽  
Author(s):  
Dokwan Lee ◽  
Ki-Taek Hong ◽  
Tae Seong Lim ◽  
Eugene Lee ◽  
Ye Hyun Lee ◽  
...  

Abstract Background: The role of altered joint mechanics on cartilage degeneration in in vivo models has not been studied successfully due to a lack of pre-injury information. We aimed 1) to develop an accurate in vivo canine model to measure the changes in joint loading and T2 star (T2*) relaxation time before and after unilateral supraspinatus tendon resections, and 2) to find the relationship between regional variations in articular cartilage loading patterns and T2* relaxation time distributions.Methods: Rigid markers were implanted in the scapula and humerus of tested dogs. The movement of the shoulder bones were measured by a motion tracking system during normal gaits. In vivo cartilage contact strain was measured by aligning 3D shoulder models with the motion tracking data. Articular cartilage T2* relaxation times were measured by quantitative MRI scans. Articular cartilage contact strain and T2* relaxation time were compared in the shoulders before and three months after the supraspinatus tendon resections.Results: Excellent accuracy and reproducibility were found in our in vivo contact strain measurements with less than 1% errors. Changes in articular cartilage contact strain exhibited similar patterns with the changes in the T2* relaxation time after resection surgeries. Regional changes in the articular cartilage T2* relaxation time exhibited positive correlations with regional contact strain variations three months after the supraspinatus resection surgeries.Conclusion: This is the first study to measure in vivo articular cartilage contact strains with high accuracy and reproducibility. Positive correlations between contact strain and T2* relaxation time suggest that the articular cartilage extracellular matrix may responds to mechanical changes in local areas.


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