Detection of tumor response to treatment in the clinic is largely based on imaging a reduction of tumor size as a marker of treatment response. However, reductions in tumor size may take several weeks and are therefore difficult to detect if a rapid evaluation of a treatment strategy is needed. Therefore, for early detection of tumor response to treatment, novel response markers are to be found. Alternative response markers, e.g. ¹⁸F-FDG-uptake, which is reduced in gastrointestinal tumors already 24 h after treatment with Imatinib, have been demonstrated but involve ionizing radiation and thus make repeated exams difficult. Further alternative techniques, such as diffusion-weighted imaging (DWI) have been shown to report on a reduction in tumor cellularity resulting in increased ADCs as a marker for treatment response that precedes reduction in tumor size. Importantly, the MRI contrast being generated using the diffusion properties of water molecules does not involve exogenous contrast agents. It therefore represents an exquisite non-invasive way to probe the tumor microenvironment using commercially available clinical MRI equipment which renders clinical translation of diffusion-based MRI protocols feasible.

In our group we optimize and develop protocols for probing diffusion microstructure in vivo using DWI for applications in oncology. ADCs and image performance are evaluated using established phantoms for ADC validation and characterisation of image artifacts. The quality of in vivo diffusion-weighted MRI acquisition heavily depends on the reduction of motion artifacts which we want to tackle both by respiratory gating and retrospective artefact reduction.

However, ADC does not always increase with successful treatment progression and is a relatively late marker of cell death only sensitive upon excessive necrosis. Therefore, there is a need for novel IBs to image early necrotic cell death.

Recently, a novel MRI contrast mechanism based on pulsed field gradient magnetic resonance methods has been introduced for in vivo measurements, which detects transmembrane water exchange, quantified by the so-called apparent exchange rate (AXR). The technique named ‘filter-exchange imaging’ (FEXI) relies on a dual diffusion-weighted MRI sequence and has been pioneered by a group of researchers from Lund University. In our recent publication in Nature Biotechnology we showed that it is even sensitive enough to pick up a small amount of ca. 100,000 cells that have been genetically modified to express water channel proteins thereby altering their transmembrane water permeability (Figure 1).