Label-Free Visualization and Quantification of Biochemical Markers of Atherosclerotic Plaque Progression Using Intravascular Fluorescence Lifetime

Mesoscopic fluorescence lifetime imaging: Fundamental principles, clinical applications and future directions

“…For uneven surfaces with flaps and creases, as well as for intraluminal imaging of small diameter vessels or airways, a point‐scanning approach may be better suited. Optical fiber‐based imaging provides the flexibility to address free‐hand scanning on small and irregular surfaces for tumor detection [109,110] as well as helical scanning for cardiovascular imaging [113,114]. The image resolution may be adapted using microscope and microendoscope objectives or distal‐end optics on fiber optic probes according to the level of detail necessary for each application [115].…”

“…The core of a recently reported FLIm instrument is compatible with multiple imaging optical fiber probes that adapt to different scanning modalities and that can couple with existing clinical tools. Examples include catheterized helical scanning mechanisms for intravascular imaging [108,113] and highly flexible free‐hand scanning during intraoperative interventions. The latter include brain tumor resection surgery, where the FLIm instrument interfaces with a neurosurgical microscope (eg, OPMI Pentero 900 (Carl Zeiss Meditec, Jena, Germany) [109]; and oral and oropharyngeal surgery for tumor removal with surgical robotic platforms (eg, da Vinci Surgical System [Intuitive Surgical, Sunnyvale, California] introducer sheaths [Si model] and graspers [SP model]) [110,123,127], which display the acquired FLIm data in an image format onto the surgeon's field‐of‐view.…”

“…Integration with ultrasound can be performed as a forward‐viewing system [128] and for intravascular imaging, also known as intravascular ultrasound (IVUS; Figure 2E). The last generation of a FLIm‐IVUS device combines an optical channel for FLIm and a 40 MHz ultrasound transducer into an 800 μm diameter rotating imaging core (overall cross‐section including imaging sheath: 3.7 Fr), suitable for the interrogation of coronary arteries in vivo [108,113].…”

“…Initial spectroscopic measurements [50, 209], followed by time‐resolved fluorescence spectroscopy and more recent FLIm technique for analysis of atherosclerosis lesions [210–214] have demonstrated how tissue autofluorescence properties enable the characterization of atherosclerotic lesions. Figure 7 depicts results from a recent study [113] conducted in coronary segments from 32 human hearts (obtained from donors/transplants). This study has provided additional insights into key biochemical and morphological features of human plaques correlated with FLIm parameters.…”

“…Intravascular FLIm enables label‐free identification of biological species associated with plaque progression (representative results); adapted from Reference [113] Left panel: lesions consistent with new plaque formation are associated with an increase in 390 nm lifetime and intensity (AIT, adaptive intimal thickening; PIT, pathological intimal thickening). Central panel: the amount of superficial mFC assessed using a semi‐quantitative scale using CD68 immunohistostaining (0, absent; 1, <10%; 2, 11%‐25%; 3, 25%‐50%; and 4, >50% of superficial 200 μm) is associated with a corresponding increase in 540 nm band lifetime.…”