Precise Deciphering of Brain Vasculatures and Microscopic Tumors with Dual NIR‐II Fluorescence and Photoacoustic Imaging

Abstract

simultaneously achieve high contrast, good spatiotemporal resolution, deep penetration, and good sensitivity. [7][8][9][10] Although conventional in vivo NIR-I brain fluorescence imaging has advantages in high sensitivity, good temporal resolution, and real-time wide-field image, it suffers from low penetration, non-negligible autofluorescence, and scattering-limited spatial resolution. [7,11] On the other hand, brain photoacoustic (PA) imaging (PAI) with reconstruction of acoustic waves generated by light absorbers after pulsed NIR laser illumination has demonstrated good ultrasonic spatial resolution, and much deeper penetration than fluorescence imaging, because ultrasound attenuates far less than light in vivo. [12] However, conventional PAI often shows severe background interference owing to the negligible tissue absorbance within NIR-I region. [9,12] In addition, multimodal brain imaging with combined desirable features of different imaging modalities could overcome shortcomings of single modality and improve diagnostic accuracy. [2,8,9,13] So far, multimodal imaging generally requires administration of different contrast agents or nanoparticles (NPs) containing multiple components, [2,8,13] which faces the challenges of different location for the former and low NP reproducibility for the latter. It is Diagnostics of cerebrovascular structures and microscopic tumors with intact blood-brain barrier (BBB) significantly contributes to timely treatment of patients bearing neurological diseases. Dual NIR-II fluorescence and photoacoustic imaging (PAI) is expected to offer powerful strength, including good spatiotemporal resolution, deep penetration, and large signal-to-background ratio (SBR) for precise brain diagnostics. Herein, biocompatible and photostable conjugated polymer nanoparticles (CP NPs) are reported for dualmodality brain imaging in the NIR-II window. Uniform CP NPs with a size of 50 nm are fabricated from microfluidics devices, which show an emission peak at 1156 nm with a large absorptivity of 35.2 L g −1 cm −1 at 1000 nm. The NIR-II fluorescence imaging resolves hemodynamics and cerebral vasculatures with a spatial resolution of 23 µm at a depth of 600 µm. The NIR-II PAI enables successful noninvasive mapping of deep microscopic brain tumors (<2 mm at a depth of 2.4 mm beneath dense skull and scalp) with an SBR of 7.2 after focused ultrasound-induced BBB opening. This study demonstrates that CP NPs are promising contrast agents for brain diagnostics. Brain ImagingClear pinpointing of cerebral vasculature and tumor structures with different morphologies and biology characteristics in complex central neural system significantly benefits patients bearing brain pathologies like neurological disorder, traumatic injury, stroke, Alzheimer's disease, and even early-and late-stage tumors. [1][2][3][4][5][6][7][8][9] Conventional neuroimaging modalities exhibit certain intrinsic limitations in each modality, which could not

Camouflaging Nanoparticles with Brain Metastatic Tumor Cell Membranes: A New Strategy to Traverse Blood–Brain Barrier for Imaging and Therapy of Brain Tumors

“…So far, some drug delivery strategies have been proposed for the transportation of cargos crossing BBB to enter the CNS, such as adsorptive‐mediated transcytosis (AMT), carrier‐mediated transport (CMT), and receptor‐mediated transcytosis (RMT). [ 6,9 ] Nanoparticles conjugating a positively charged moiety, such as a cell penetrating peptide (CPP), can contact with the membrane surface of BBB (with negative charge) to traverse the BBB by AMT. [ 5,10 ] But the ability of such nanoparticles to traverse the BBB is relatively low because of limited affinity, lack of selectivity, and easy immune clearance.…”

NIR-II fluorescence microscopic imaging of cortical vasculature in non-human primates

“…Thus far, several types of NIR-II fluorescent probes, including carbon nanotubes 34 , rare-earth doped nanoparticles 35 , quantum dots 36 , small-molecule organic dyes 37 and organic nanoparticles 38,39 , have been utilized for in vivo imaging of small animals.…”

Recent Progress in NIR-II Contrast Agent for Biological Imaging

“…At present, this field has become a vital resource for biomedical diagnosis and treatment, and many research groups are competing to continue pushing forward in expanding its study. Several high-level research papers and reviews have been reported recently, such as Guo et al (2019), who used NIR-II fluorescence and photoacoustic imaging to study the precise identification of the vascular system and micro-tumors in 2019. It is well-known that the diagnosis of cerebrovascular structure with complete blood-brain barrier and microtumors is of great significance for the timely treatment of patients with nervous system diseases.…”