Blood flow in murine epicardial and intra-myocardial coronary arteries was measured in vivo with spectral domain optical Doppler tomography (SD-ODT). Videos at frame rates up to 180 fps were collected and processed to extract phase shifts associated with moving erythrocytes in the coronary arteries. Radial averaging centered on the vessel lumen provided spatial smoothing of phase noise in a single cross-sectional frame for instantaneous peak velocity measurement without distortion of the flow profile. Temporal averaging synchronized to the cardiac cycle (i.e., gating) was also performed to reduce phase noise, although resulting in lower flow profiles. The vessel angle with respect to incident imaging beam was measured with three-dimensional raster scans collected from the same region as the high speed cross-sectional scans. The variability in peak phase measurement was 10-15% from cycle to cycle on a single animal but larger for measurements among animals. The inter-subject variability is attributed to factors related to real physiological and anatomical differences, instrumentation variables, and measurement error. The measured peak instantaneous flow velocity in a ~40-µm diameter vessel was 23.5 mm/s (28 kHz Doppler phase shift). In addition to measurement of the flow velocity, we observed several dynamic features of the vessel and surrounding myocardium in the intensity and phase sequences, including asymmetric vessel deformation and rapid flow reversal immediately following maximum flow, in confirmation of known coronary artery flow dynamics. SD-ODT is an optical imaging tool that can provide in vivo measures of structural and functional information on cardiac function in small animals.

A new concept for cancer screening has been preliminarily investigated. A cancer targeting agent loaded with a near-infrared (NIR) dye was topically applied on the tissue to highlight cancer-suspect locations and guide optical coherence tomography (OCT) imaging, which was used to further investigate tissue morphology at the micron scale. A pilot study on ApcMin mice has been performed to preliminarily test this new cancer screening approach. As a cancer-targeting agent, poly(epsilon-caprolactone) microparticles (PCLMPs), labeled with a NIR dye and functionalized with an RGD (argenine-glycine-aspartic acid) peptide, were used. This agent recognizes the ανβ3 integrin receptor (ABIR), which is over-expressed by epithelial cancer cells. The contrast agent was administered topically in vivo in mouse colon. After incubation, the animals were sacrificed and fluorescence-guided high resolution optical coherence tomography (OCT) imaging was used to visualize colon morphology. The preliminary results show preferential staining of the abnormal tissue, as indicated by both microscopy and laser-induced fluorescence imaging, and OCT’s capability to differentiate between normal mucosal areas, early dysplasia, and adenocarcinoma. Although very preliminary, the results of this study suggest that fluorescence-guided OCT imaging might be a suitable approach for cancer screening. If successful, this approach could be used by clinicians to more reliably diagnose early stage cancers in vivo.

A new type of freeze-drying microscope based upon time-domain optical coherence tomography is presented here (OCT-FDM). The microscope allows for real-time, in situ 3D imaging of pharmaceutical formulations in vials relevant for manufacturing processes with a lateral resolution of <7 μm and an axial resolution of <5 μm. Correlation of volumetric structural imaging with product temperature measured during the freeze-drying cycle allowed investigation of structural changes in the product and determination of the temperature at which the freeze-dried cake collapses. This critical temperature is the most important parameter in designing freeze-drying processes of pharmaceutical products.

We demonstrate for the first time that optical coherence tomography (OCT) imaging can reliably distinguish between morphologic features of low risk pancreatic cysts (i.e., pseudocysts and serous cystadenomas) and high risk pancreatic cysts (i.e., mucinous cystic neoplasms and intraductal papillary mucinous neoplasms). In our study fresh pancreatectomy specimens (66) from patients with cystic lesions undergoing surgery were acquired and examined with OCT. A training set of 20 pathology-OCT correlated tissue specimens were used to develop criteria for differentiating between low and high risk cystic lesions. A separate (validation) set of 46 specimens were used to test the OCT criteria by three clinicians, blinded to histopathology findings. Histology was finally used as a ‘gold’ standard for testing OCT findings. OCT was able to reveal specific morphologic features of pancreatic cysts and thus to differentiate between low-risk and high-risk cysts with over 95% sensitivity and specificity. This pilot study suggests that OCT could be used by clinicians in the future to more reliably differentiate between benign and potentially malignant pancreatic cysts. However, in vivo use of OCT requires a probe that has to fit the bore of the pancreas biopsy needle. Therefore, we have developed such probes and planned to start an in vivo pilot study within the very near future.