Water and lipids are key participants in many biological processes, but there are few non-invasive methods that provide quantification of these components in vivo, and none that can isolate and quantify lipids in the blood. Here we develop a new imaging modality termed shortwave infrared meso-patterned imaging (SWIR-MPI) to provide label-free, non-contact, spatial mapping of water and lipid concentrations in tissue. The method utilizes patterned hyperspectral illumination to target chromophore absorption bands in the 900–1,300 nm wavelength range. We use SWIR-MPI to monitor clinically important physiological processes including edema, inflammation, and tumor lipid heterogeneity in preclinical models. We also show that SWIR-MPI can spatially map blood-lipids in humans, representing an example of non-invasive and contact-free measurements of in vivo blood lipids. Together, these results highlight the potential of SWIR-MPI to enable new capabilities in fundamental studies and clinical monitoring of major conditions including obesity, cancer, and cardiovascular disease.

Biomechanical alterations to the tumor microenvironment include accumulation of solid stresses, extracellular matrix (ECM) stiffening and increased fluid pressure in both interstitial and peri-tumoral spaces. The relationship between interstitial fluid pressurization and ECM remodeling in vascularized tumors is well characterized, while earlier biomechanical changes occurring during avascular tumor growth within the peri-tumoral ECM remain poorly understood. Type I collagen, the primary fibrous ECM constituent, bears load in tension while it buckles under compression. We hypothesized that tumor-generated compressive forces cause collagen remodeling via densification which in turn creates a barrier to convective fluid transport and may play a role in tumor progression and malignancy. To better understand this process, we characterized the structure-function relationship of collagen networks under compression both experimentally and computationally. Here we show that growth of epithelial cancers induces compressive remodeling of the ECM, documented in the literature as a TACS-2 phenotype, which represents a localized densification and tangential alignment of peri-tumoral collagen. Such compressive remodeling is caused by the unique features of collagen network mechanics, such as fiber buckling and cross-link rupture, and reduces the overall hydraulic permeability of the matrix.

Significance: The shortwave infrared (SWIR) optical window (∼900 to 2000 nm) has attracted interest for deep tissue imaging due to the lower scattering of light. SWIR spatial frequency domain imaging (SWIR SFDI) provides wide-field tissue optical property measurements in this wavelength band. Key design and performance characteristics, such as portability, wavelength selection, measurement resolution, and the effect of skin have not yet been addressed for SWIR SFDI.Aim: To fabricate and characterize a SWIR SFDI system for clinical use. Approach:The optimal choice of wavelengths was identified based on optical property uncertainty estimates and imaging depth. A compact light-emitting diode-based dual wavelength SWIR SFDI system was fabricated. A two-layer inverse model was developed to account for the layered structure of skin. Performance was validated using tissue-simulating phantoms and in-vivo measurements from three healthy subjects.Results: The SWIR SFDI system had a μ 0 s resolution of at least 0.03 mm −1 at 880 nm and 0.02 mm −1 at 1100 nm. The two-layer inverse model reduced the error in deeper layer μ 0 s extractions by at least 24% in the phantom study. The two-layer model also increased the contrast between superficial vessels and the surrounding tissue for in-vivo measurements. Conclusion:The clinic-ready SWIR SFDI device is sensitive to small optical property alterations in diffuse media, provides enhanced accuracy in quantifying optical properties in the deeper layers in phantoms, and provided enhanced contrast of subcutaneous blood vessels.

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Systemic sclerosis (SSc) is an autoimmune disease characterized by the widespread deposition of excess collagen in the skin and internal organs, as well as vascular dysfunction. The current standard of care technique used to quantify the extent of skin fibrosis in SSc patients is the modified Rodnan skin score (mRSS), which is an assessment of skin thickness based on clinical palpation. Despite being considered the gold standard, mRSS testing requires a trained physician and suffers from high inter-observer variability. In this study, we evaluated the use of spatial frequency domain imaging (SFDI) as a more quantitative and reliable method for assessing skin fibrosis in SSc patients. SFDI is a wide-field and non-contact imaging technique that utilizes spatially modulated light to generate a map of optical properties in biological tissue. The SFDI data were collected at six measurement sites (left and right forearms, hands, and fingers) of eight control subjects and ten SSc patients. mRSS were assessed by a physician, and skin biopsies were collected from subject’s forearms and used to assess for markers of skin fibrosis. Our results indicate that SFDI is sensitive to skin changes even at an early stage, as we found a significant difference in the measured optical scattering (μs′) between healthy controls and SSc patients with a local mRSS score of zero (no appreciable skin fibrosis by gold standard). Furthermore, we found a strong correlation between the diffuse reflectance (R d ) at a spatial frequency of 0.2 mm−1 and the total mRSS between all subjects (Spearman correlation coefficient = -0.73, p-value < 0.0028), as well as high correlation with histology results. The healthy volunteer results show excellent inter- and intra-observer reliability (ICC > 0.8). Our results suggest that the measurement of tissue μs′ and R d at specific spatial frequencies and wavelengths can provide an objective and quantitative assessment of skin involvement in SSc patients, which could greatly improve the accuracy and efficiency of monitoring disease progression and evaluating drug efficacy.