There is provided a non-invasive method of generating image data of intra-cranial tissue using ultrasound energy that is transmitted across a head of a subject throughthe skull of the subject. The method comprises the steps of: a) providing an ultrasound observed data set derived from a measurement of one or more ultrasound waveforms generated by at least one source of ultrasound energy, the ultrasound energy being detected by a plurality of receivers located at an opposing side of a region within the intra-cranial cavity with respect to at least one source such that thereceivers detect ultrasound waveforms from the source which have been transmitted through the skull and intra-cranial cavity, the observed data set comprising a plurality of observed data values; b) providing at least one starting model for at least a portion of the head comprising a skull component and a soft tissue component, the skull component comprising a plurality of model parameters representative of the physicalproperties and morphology of the skull through which intra-cranial tissue is being imaged, and the soft tissue component comprising a plurality of parameters representative of the physical properties of the intra-cranial tissue being imaged; c) generating a predicted data set comprising a plurality of predicted data values from the starting model of the skull and of the intra-cranial tissue; d) comparing theobserved and predicted data values in order to generate an updated model of at least one physical property within at least a region of the intra-cranial cavity possibly by full waveform inversion analysis and e) using the updated model to image a region of the inter-cranial cavity to identify tissue composition and/or morphology within the intra-cranial cavity. The invention may also be applied to imaging other body regions containing at least on interface between bone, soft tissue or gas.