## 4 Clinical Relevance of Non-Invasive Imaging Probes  
The ability to image the individual components of the ECM to gain an insight into the live biological processes that ultimately manifest as various CVDs is of great clinical value. The clinical translational scope is multifaceted. Patients can be identified at an earlier stage in the disease process, potentially prior to phenotypical or symptomatic presentation. This will subsequently enable the initiation of either prophylactic or therapeutic treatment at a much earlier stage, which may translate into improved clinical outcomes. The dynamic nature of ECM biology can be leveraged to monitor patients over time, including their response to treatment. Furthermore, the quantitative and targeted imaging of ECM components could be utilised as an additional tool to titrate and if needed alter therapeutic strategies. Similarly, molecular imaging of ECM components could play a significant role in therapeutic drug development both in pre-clinical and clinical trials to assess the efficacy of pharmacological interventions at both the cellular and molecular levels.  
However, these probes are largely still at the developmental stage and no single probe has yet been established for routine clinical decision-making. They remain expensive to implement and are mainly used by a select group of academic and commercial institutions. In addition to large clinical efficacy trials, long-term data on the potential effect these imaging probes may have on the physiological function of the ECM is required before large-scale clinical trials take place. Nuclear imaging probes have a distinct advantage over MRI probes in the sense that a significantly lower concentration of probe is required to achieve the required threshold for detection. This lowers the developmental cost of probes and accelerates human trials as expensive and time-consuming toxicity studies in humans can often be extenuated due to micromolar dosing. However, MRI retains the advantage of superior spatial resolution, intrinsic tissue characterisation and lack of ionising radiation. Furthermore, once the initial hurdle of probe safety and efficacy has been overcome, long-term production, storage and maintenance of MRI probes is cheaper and more scalable compared to nuclear imaging probes, for instance no requirement for cyclotrons in close proximity to scanners, longer and safer storage once manufactured. Furthermore, access to MRI scanners is relatively cheaper compared to PET. Hybrid scanners (e.g., PET/MR) have been developed to take advantage of the higher sensitivity of PET whilst at the same time enjoying the benefits of MRI (e.g., higher spatial resolution). However, they are very expensive, limited to a select group of centres and ionising radiation remains a persistent drawback.  
One area that is attracting interest is the idea of using ECM probes with PET in clinical proof of concept studies by taking advantage of the significantly lower dose that is required as a pragmatic bridge to full MRI only probe development. Once a clear proof of concept in man is established, resources and focus can shift towards toxicity and safety studies for MRI only probes. This strategy can streamline the pathway and significantly increase the likelihood of successful probe development.