A microscope (1; 1'; 1"; 1'") for high spatial resolution imaging a structure of interest in a sample comprising a substance, said substance having a first state with first spectral properties and a second state with second spectral properties, the microscope (1; 1'; 1 "; 1'") comprising: - an objective-lens assembly having first and second sides opposite to each other, and presenting first and second focal planes respectively on said first and second sides, the sample being intended to be placed on the first side, - a transfer light source (4,4b) arranged on the second side of the objective-lens assembly to emit a transfer light beam towards the sample through the objective-lens assembly, said transfer light beam having an intensity and a phase profile, - a light beam modulating device placed between the transfer light source (4,4b) and the objective-lens assembly, said light beam modulating device being adapted to spatially vary the transfer light beam so that said transfer light beam after having passed trough said light beam modulating device and the objective-lens assembly presents at least a first intensity area with a first intensity adapted to transfer the substance in the second state to the first state, and at least a second intensity area with a second intensity adapted not to transfer the substance between the first and second states, - a probe detector adapted to detect an optical measurement signal from a portion of the substance in the second state, said microscope (1; 1'; 1"; 1'") being characterised in that it comprises a phase contrast microscopy system which includes: - the light beam modulating device further adapted to generate a phase contrast, - an illuminating light source arranged to emit an illuminating light beam (17; 5b) towards the sample, wherein said illuminating light source either coincides with the transfer light source (4,4b) or is a separate light source, said illuminating light beam (17; 5b) having an intensity and a phase profile, - an intensity detector arranged to detect the intensity of the illuminating light beam (17; 5b) after said illuminating light beam (17; 5b) has passed at least once through the sample, the objective lens assembly and the light beam modulating device. - an objective-lens assembly having first and second sides opposite to each other, and presenting first and second focal planes respectively on said first and second sides, the sample being intended to be placed on the first side, - a transfer light source (4,4b) arranged on the second side of the objective-lens assembly to emit a transfer light beam towards the sample through the objective-lens assembly, said transfer light beam having an intensity and a phase profile, - a light beam modulating device placed between the transfer light source (4,4b) and the objective-lens assembly, said light beam modulating device being adapted to spatially vary the transfer light beam so that said transfer light beam after having passed trough said light beam modulating device and the objective-lens assembly presents at least a first intensity area with a first intensity adapted to transfer the substance in the second state to the first state, and at least a second intensity area with a second intensity adapted not to transfer the substance between the first and second states, - a probe detector adapted to detect an optical measurement signal from a portion of the substance in the second state, - the light beam modulating device further adapted to generate a phase contrast, - an illuminating light source arranged to emit an illuminating light beam (17; 5b) towards the sample, wherein said illuminating light source either coincides with the transfer light source (4,4b) or is a separate light source, said illuminating light beam (17; 5b) having an intensity and a phase profile, - an intensity detector arranged to detect the intensity of the illuminating light beam (17; 5b) after said illuminating light beam (17; 5b) has passed at least once through the sample, the objective lens assembly and the light beam modulating device.