The sensitive and specific detection of premalignant and malignant lesions is a crucial and indispensable prerequisite for optimal treatment outcome and prognosis. Surgical biopsy, which is currently the primary diagnostic tool, often causes patient anxiety and discomfort, undesirable side effects, and sampling errors. For example, multiple prostate biopsies miss up to 30% of cancer present at the time of biopsy.^{1, 2, 3} An urgent need exists to develop cost-effective, minimally invasive imaging technologies to identify premalignancy and malignancy with high sensitivity and specificity.⁴ Optical imaging tools such as reflectance confocal microscopy, optical coherence tomography (OCT), and optical coherence microscopy (OCM) are promising diagnostic tools for detecting cancer at an early stage.⁵ Optical imaging is particularly useful for in vivo applications because it uses near-infrared wavelengths $\left(770\text{to}1300\mathrm{nm}\right)$ that avoid predominant absorption in tissue.⁶

We demonstrate a fiber-based probe for maximum collection of the coherent anti-Stokes Raman scattering (CARS) signal in biological tissues. We discuss the design challenges including capturing the back-scattered forward generated CARS signal in the sample and the effects of fiber nonlinearities on the propagating pulses. Three different single mode fibers (fused silica fiber, photonic crystal fiber and double-clad photonic crystal fiber) were tested for the probe design. We investigated self-phase modulation, stimulated Raman scattering (SRS) and four-wave-mixing (FWM) generation in the fiber: nonlinear processes expected to occur in a two-beam excitation based probe. While SPM and SRS induced spectral broadening was negligible, a strong non phase-matched FWM contribution was found to be present in all the tested fibers for excitation conditions relevant to CARS microscopy of tissues. To spectrally suppress this strong contribution, the probe design incorporates separate fibers for excitation light delivery and for signal detection, in combination with dichroic optics. CARS images of the samples were recorded by collecting the back-scattered forward generated CARS signal in the sample through a multi-mode fiber. Different biological tissues were imaged ex vivo in order to assess the performance of our fiber-delivered probe for CARS imaging, a tool which we consider an important advance towards label-free, in vivo probing of superficial tissues.

Lipid deposition inside the arterial wall is a key indicator of plaque vulnerability. An intravascular photoacoustic (IVPA) catheter is considered a promising device for quantifying the amount of lipid inside the arterial wall. Thus far, IVPA systems suffered from slow imaging speed (~50 s per frame) due to the lack of a suitable laser source for high-speed excitation of molecular overtone vibrations. Here, we report an improvement in IVPA imaging speed by two orders of magnitude, to 1.0 s per frame, enabled by a custom-built, 2-kHz master oscillator power amplifier (MOPA)-pumped, barium nitrite [Ba(NO₃)₂] Raman laser. This advancement narrows the gap in translating the IVPA technology to the clinical setting.

We compare, in detail, the phase-resolved color Doppler (PRCD), phase-resolved Doppler variance (PRDV) and intensity-based Doppler variance (IBDV) methods. All the methods are able to quantify flow speed when the flow rate is within a certain range, which is dependent on the adjacent A-line time interval. While PRCD is most sensitive when the flow direction is along the probing beam, PRDV and IBDV can be used to measure the flow when the flow direction is near perpendicular to the probing beam. However, the values of PRDV and IBDV are Doppler angle-dependent when the Doppler angle is above a certain threshold. The sensitivity of all the methods can be improved by increasing the adjacent A-line time interval while still maintaining a high sampling density level. We also demonstrate for the first time, to the best of our knowledge, high resolution inter-frame PRDV method. In applications where mapping vascular network such as angiogram is more important than flow velocity quantification, IBDV and PRDV images show better contrast than PRCD images. The IBDV and PRDV show very similar characteristics and demonstrate comparable results for vasculature mapping. However, the IBDV is less sensitive to bulk motion and with less post-processing steps, which is preferred for fast data processing situations. In vivo imaging of mouse brain with intact skull and human skin with the three methods were demonstrated and the results were compared. The IBDV method was found to be able to obtain high resolution image with a relative simple processing procedure.

Optical coherence tomography (OCT) is an evolving imaging modality that combines interferometry with low-coherence light to produce high-resolution tissue imaging. Cross-sectional in vivo images were obtained using an OCT device consisting of a Michelson interferometer, 1.3-μm broadband light source, and a handheld fiberoptic imaging probe. Image pixel resolution approached 10 μm. The mucosa of the oral cavity and oropharynx were examined in 41 patients during operative endoscopy. Optical coherence tomographic imaging was combined with endoscopic photography for gross and histologic image correlation. Optical coherence tomographic images of the oral cavity and oropharynx provided microanatomical information on the epithelium, basement membrane (BM), and supporting lamina propria (LP) of the mucosa. Normal microstructures identified in these tissues included an overlying keratin layer, papillae, ducts, glands, and blood vessels. Regions of pathologic features studied included mature scar, granulation tissue, mucous cysts, leukoplakia, and invasive cancer. Optical coherence tomographic imaging showed distinct zones of normal, altered, and ablated tissue microstructures for each pathologic process studied. Abnormal findings were directly compared with regions of normal tissue or conventional histopathologic features when tissue for analysis was available. This study provides a composite series of in vivo OCT images of the oral cavity and oropharynx in a variety of normal regions and pathologic states as well as outline future applications of OCT technology.

Optical coherence tomography is an emerging non-invasive technology that provides high resolution, cross-sectional tomographic images of internal structures of specimens. OCT images, however, are usually degraded by significant speckle noise. Here we introduce to our knowledge the first 3D approach to attenuating speckle noise in OCT images. Unlike 2D approaches which only consider information in individual images, 3D processing, by analyzing all images in a volume simultaneously, has the advantage of also taking the information between images into account. This, coupled with the curvelet transform’s nearly optimal sparse representation of curved edges that are common in OCT images, provides a simple yet powerful platform for speckle attenuation. We show the approach suppresses a significant amount of speckle noise, while in the mean time preserves and thus reveals many subtle features that could get attenuated in other approaches.