## 4 PAI in Combination with Other Imaging Techniques  
Both multimodal imaging and detection are increasingly used in practical applications to ensure an enhanced accuracy and/or to attain more comprehensive answers to targeted questions. [PERSON] et al. designed and synthesized a multifunctional probe using a NIR ultra-high absorbing croonium dye for amyloid (CDA), which can be used to strongly bind the hydrophobic channels of cerebrovascular amyloid beta (A\(\beta\)) fibers. Labelled with radioactive 18F, the multifunctional probe allowed for the ultrasensitive PAT/positron emission tomography (PET)/fluorescence imaging (FI) of A\(\beta\) plaques in the brain cortex [77]. PAT has been used in multimodal detection to image pathological sites on cortical vessels with a high spatial resolution and optical specificity, whereas PET has revealed a whole-body anatomy with quantitative biodistribution information. PAT has also been employed in combination with fluorescence molecular imaging (FMI) to non-invasively detect tumours through an intact skull, by combining targeted cancer stem cells nanoparticles. These nanoparticles accumulated specifically in the tumour area, allowing glioma to be precisely revealed at the cellular level [78]. This combination of optical PAT and FMI navigation fulfilled the promise of precise visual imaging in glioma detection and the resection in deep tissue. Mesenchymal stem cells (MSCs) have been used in a variety of successful applications against glioblastoma multiform (GBM) identifying brain tumours. A recent development involves gold-coated superparamagnetic iron oxides (SPIO) loaded with bone marrow-derived MSC nanoparticles (SPIO@Au-loaded MSCs) which were used in PA and magnetic resonance (MR) dual-modal imaging [79]. The synthesized SPIO@Au-loaded MSCs function as contrast enhancing agents for PA and MR, because gold nanoshells produce surface plasmon resonance in the NIR region, while SPIO nanocores produce strong MR signals through the skull. The experiments revealed that carotid artery-injected MSCs labelled with SPIO@Au at 4 ug/mL did not induce cell death or any adverse effects on differentiation or migration, and could be tracked in vivo via MR and PA imaging. This provides a powerful tool for the design and real-time monitoring of stem cell-mediated brain tumour therapies. It is also worth noting that gold nanoshells on nanoparticle surfaces permitted the use of laser ablation to kill cancer cells, as in photothermal ablation therapy. Based on the research above, it appears integrating the nanocomposite design with the multimodal imaging capabilities of PAI, FI and MR imaging (MRI) offers multiple advantages for the sensitive imaging of early-stage glioblastoma tumours, while compensating for the limitations of each imaging modality. Recently, [PERSON] et al. developed multifunctional nanoagents, based on NIR light-absorbing and NIR-emissive small molecules (TC1), and integrated them with ultra-small iron oxide nanoparticles (UIONPs) [80]. To resolve the fluorescence quenching problem induced by the immediate proximity of UIONPs and the TC1, they fabricated HALF (which is the nanocomposite volume to be half-occupied by UIONPs) to create spatial distance between the two components. Decorated with a peptide ligand cRGD for improved brain tumour targeting, HALF-cRGD was demonstrated, experimentally, to be a good imaging contrast agent in multimodal imaging (FI, PAI and MRI) and an effective photothermal therapeutic agent for brain tumours. [PERSON] et al. used multimodal techniques, combining real-time non-invasive bioluminescence imaging (BLI), high-resolution in vivo PAI and neuropathological analyses to provide an accurate validation of traumatic brain injury (TBI) pathology, by subjecting NFxB-RE-Luc transgenic male and female mice to TBI (Model #10,499, Ta-conic Biosciences, Rensselaer, NY, USA) [81].