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Methods

BOLD Contrast

BOLD(Blood Oxygen Level Dependent) was first shown in vivo  by Ogawa et al, it is based on the difference in magnetic properties between two oxygenation states of hemoglobin. Deoxyhemoglobin is paramagnetic and introduces an inhomogeneity into the nearby magnetic field, whereas oxyhemoglobin is weakly diamagnetic and has little effect.
Based on the inherent paramagnetic properties of deoxyhemoglobin one can derive susceptibility-weighted (T2*) or transverse relaxation−weighted (T2). Detection and imaging in vivo rely on spatial and temporal changes in blood oxygenation, flow and volume. In the field of cancer BOLD-contrast MRI has been applied monitoring tumor response to vasomodulators, analysis of tumor vessel functionality, maturation, and angiogenesis. (Rinat Abramovitch, 1998, Carmeliet P., 1998, Michal Neeman, 2001)

Blood volume

(Rinat Abramovitch, 1998)

Permeability

MRI OF LYMPHATIC CLEARANCE

In normal tissue macromolecules are cleared from the interstitial space through the lymphatic vessels.  In tumors, where the lymphatics are frequently not functional, material drainage occurs from the tumor rim, through peritumor lymphatics. Administration of macromolecular contrast material, either   interstitially or intravenously, enables us to follow this drainage pathway. In the MRI Lymphatic drain can be detected as delayed enhancement in regions found downstream of the permeable vessels. Kinetic analysis of contrast enhancement can be used to map the direction and rate of lymphatic drain.
When contrast material is introduced intravenously, the slow process of lymphatic drain is masked by the signal originating from vascular permeability which is much faster. In order to overcome this signal masking we use avidin chase. The intravenous injection of the contrast material is followed by an injection of avidin, the biotinylated contrast material (biotin-BSA-GdDTPA) is linked to the avidin and rapid clearance is performed by liver and spleen macrophages. The area which remains highlighted after the avidin chase is where vascular hyperpermeability is present. Clearance of the interstitial contrast material allows  us to follow the rate and direction of lymphatic clearance.
(Hagit Dafni, 2002, Hagit Dafni, 2002, Hagit Dafni, 2003)

Cell tracking

(Dorit Granot, 2007)

Reporter gene

(Batya Cohen, 2007, Batya Cohen, 2005, Z. Gottesfeld and Neeman M, 1996)

ECM remodeling

(Liora Shiftan, 2005, Liora Shiftan, 2006, Galit Mazooz, 2005)