Current imaging techniques capable of tracking nanoparticles in vivo supply either a large field of view or cellular resolution, but not both. Here, we demonstrate a multimodality imaging platform of optical coherence tomography (OCT) techniques for high resolution, wide field of view in vivo imaging of nanoparticles. This platform includes the first in vivo images of nanoparticle pharmacokinetics acquired with photothermal OCT (PTOCT), along with overlaying images of microvascular and tissue morphology. Gold nanorods (51.8 ± 8.1 nm by 15.2 ± 3.3 nm) were intravenously injected into mice, and their accumulation into mammary tumors was non-invasively imaged in vivo in three dimensions over 24 hours using PTOCT. Spatial frequency analysis of PTOCT images indicated that gold nanorods reached peak distribution throughout the tumors by 16 hours, and remained well-dispersed up to 24 hours post-injection. In contrast, the overall accumulation of gold nanorods within the tumors peaked around 16 hours post-injection. The accumulation of gold nanorods within the tumors was validated post-mortem with multiphoton microscopy. This shows the utility of PTOCT as part of a powerful multimodality imaging platform for the development of nanomedicines and drug delivery technologies.

HER2-amplified (HER2 + ) breast cancers are treated with the anti-HER2 monoclonal antibody trastuzumab. Although trastuzumab reduces production of the angiogenic factor VEGF in HER2 + tumors, the acute and sustained effects of trastuzumab on the tumor vasculature are not understood fully, particularly in trastuzumab-resistant tumors. We used mouse models of trastuzumab sensitive and trastuzumab-resistant HER2 + breast cancers to measure dynamic changes in tumor microvessel density and hemoglobin oxygenation (sO 2 ) in vivo using quantitative hyperspectral imaging at 2, 5, 9, and 14 days after antibody treatment. Further analysis quantified the distribution of microvessels into low and high oxygenation groups, and monitored changes in these distributions with trastuzumab treatment. Gold standard immunohistochemistry was performed to validate complementary markers of tumor cell and vascular response to treatment. Trastuzumab treatment in both responsive and resistant tumors resulted in decreased sO 2 5 days after initial treatment when compared to IgG-treated controls (p<0.05). Importantly, responsive tumors showed significantly higher vessel density and significantly lower sO 2 than all other groups at 5 days post-treatment (p<0.05). Distribution analysis of vessel sO 2 showed a significant (p<0.05) shift of highly oxygenated vessels towards lower oxygenation over the time-course in both trastuzumab-treated responsive and resistant tumors. This study suggests that longitudinal hyperspectral imaging of microvessel sO 2 and density could distinguish trastuzumabresponsive from trastuzumab-resistant tumors, a finding that could be exploited in the post-neoadjuvant setting to guide post-surgical treatment decisions. Udove, A. Ullrich, and et, "Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer," Science 244(4905), 707-712 (1989). 3. J. S. Ross and J. A. Fletcher, "The HER-2/neu oncogene in breast cancer: prognostic factor, predictive factor, and target for therapy," Stem Cells 16(6), 413-428 (1998) ©2014 Optical Society of America

Poole KM, Tucker-Schwartz JM, Sit WW, Walsh AJ, Duvall CL, Skala MC. Quantitative optical imaging of vascular response in vivo in a model of peripheral arterial disease. Am J Physiol Heart Circ Physiol 305: H1168 -H1180, 2013. First published August 16, 2013 doi:10.1152/ajpheart.00362.2013.-The mouse hind limb ischemia (HLI) model is well established for studying collateral vessel formation and testing therapies for peripheral arterial disease, but there is a lack of quantitative techniques for intravitally analyzing blood vessel structure and function. To address this need, non-invasive, quantitative optical imaging techniques were developed to assess the timecourse of recovery in the mouse HLI model. Hyperspectral imaging and optical coherence tomography (OCT) were used to non-invasively image hemoglobin oxygen saturation and microvessel morphology plus blood flow, respectively, in the anesthetized mouse after induction of HLI. Hyperspectral imaging detected significant increases in hemoglobin saturation in the ischemic paw as early as 3 days after femoral artery ligation (P Ͻ 0.01), and significant increases in distal blood flow were first detected with OCT 14 days postsurgery (P Ͻ 0.01). Intravital OCT images of the adductor muscle vasculature revealed corkscrew collateral vessels characteristic of the arteriogenic response to HLI. The hyperspectral imaging and OCT data significantly correlated with each other and with laser Doppler perfusion imaging (LDPI) and tissue oxygenation sensor data (P Ͻ 0.01). However, OCT measurements acquired depth-resolved information and revealed more sustained flow deficits following surgery that may be masked by more superficial measurements (LDPI, hyperspectral imaging). Therefore, intravital OCT may provide a robust biomarker for the late stages of ischemic limb recovery. This work validates non-invasive acquisition of both functional and morphological data with hyperspectral imaging and OCT. Together, these techniques provide cardiovascular researchers an unprecedented and comprehensive view of the temporal dynamics of HLI recovery in living mice. peripheral arterial disease; hyperspectral imaging; optical coherence tomography; ischemia; intravital imaging PERIPHERAL ARTERIAL DISEASE (PAD) affects an estimated 8 million Americans and is associated with increased risk of myocardial infarction, stroke, and reduced quality of life (1,40,53). Development of novel PAD treatments that are less invasive and more effective than the current standard of care is a significant focus within basic and clinical cardiovascular research. Although promising results from preclinical studies have justified translation of pro-angiogenic therapies, recent clinical trials have yielded only mildly encouraging, insignificant trends toward improvement in secondary endpoints (17,28,31,33,38). There are several factors that may contribute to the disparity between successful preclinical studies and unsuccessful clinical trials. For example, novel therapeutic strategies are often evaluated with the mo...

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