LAMMP Technology Cores
Diffuse Optical Technologies
The Diffuse Optical Technologies Core (DOT) couples spatial, spectral, and temporal frequency modulation techniques with advanced computational models to provide access to absolute quantitation of absorption, scattering, fluorescence and speckle contrast.Two primary technological approaches:
Wide-field Functional Imaging (WiFI)
non-contact functional imaging of superficial tissues (<5mm)
Diffuse Optical Spectroscopy and Imaging (DOSI)
fiber-based functional imaging of deep tissues (>5mm)
Quantitative characterization of tissue structure and function across spatial scales is one of the most challenging problems in Medical Imaging. Field of view, depth of interrogation, and resolution are critical features that dramatically impact image quality and information content. Optical methods can potentially provide a single platform for imaging biological tissues with resolution and depth sensitivity from microns to centimeters, limited by fundamental light-tissue interactions.
The broad goal of the Wide-field Functional Imaging (WiFI) core is to develop an integrated imaging platform capable of quantitative subsurface metabolic imaging across spatial scales.
WiFI will simultaneously measure tissue blood flow, biochemical composition (i.e. oxy- and deoxy- hemoglobin, water and lipid content), and molecular fluorescence in turbid tissues. It will possess sufficient spatio-temporal resolution to study both fast (i.e., ms timescale) and localized (i.e., tens of µm to mm) events at depths of several millimeters in thick tissues. This platform will enable quantitative insight into disease progression and therapeutic response in areas such as wound healing, neuroscience and cancer. To achieve this objective, we propose to design and fabricate a series of instruments based on the integration of two wide-field imaging modalities that have been developed over the course of the most recent LAMMP funding period: spatial frequency domain imaging (SFDI; aka Modulated Imaging, MI); both reflectance and fluorescence imaging modes and laser speckle imaging (LSI).
SFDI Images of laser treated port wine stain (PWS): SFDI derived PWS data for subject 1 (measurement 1a). Collage of pre-operative (left) and postoperative (right) (a) color images, t (b) absorption map, (c) scattering map, (d) deoxy-hemoglobin maps, (e) total hemoglobin and (f) tissue oxygen saturation. Elevated ctTHb and stO2 (relative to surrounding normal skin) are seen in lesion prior to laser treatment. An increase in ctHHb, ctTHb, and decrease in stO2 (relative to pre-treatment concentrations) is evident immediately after treatment. From: Spatial frequency domain imaging of port wine stain biochemical composition in response to laser therapy: A pilot study. Mazhar A, Sharif SA, Cuccia JD, Nelson JS, Kelly KM, Durkin AJ. Lasers Surg Med. 2012 Aug 21.
Diffuse Optical Spectroscopic Imaging (DOSI) is a technology designed to "see" metabolic tissue function and tissue architecture deep below tissue surfaces. DOSI provides high spectral resolution (as with MRS) with a low spatial resolution of functional quantities (as with PET) using a handheld probe and portable interface (as with ultrasound). We are heavily engaged in translational research, where we conceptualize, construct, and test unique instruments designed to solve important medical/biomedical problems.
DOSI instruments are designed to visualize tissue structures and functional events deep below the surface of tissues (~ cm) with low spatial resolution (5-10mm) and high metabolic sensitivity. The spectral dependence of absorption and scattering contains rich functional and structural detail that can quantify molecular composition and morphology. DOSI methods employ broadband near infrared (NIR) spectra (650-1050 nm) improve the recovered biochemical information for multiple tissue constituents (e.g. oxy- and deox- hemoglobin, methemoglobin, water, lipid, and cytochromes), as well as functionally-relevant variations in molecular state. These technologies are fast enough to characterize hemodynamic processes (ms timescale) and robust enough to facilitate longitudinal studies (over several months) where each subject serves as its own control.
2D maps of tumor metabolism derived from tissue optical properties are generated by measuring broadband absorption and scattering spectra (650-1000 nm) along a grid of discrete points on the surface of the breast. On the left is a grid (spacing 10 mm) with each dot representing a DOSI measurement site where broadband absorption and scattering spectra were acquired. On the right, maps of tissue optical index (TOI=ctHHbxctH2O/ctLipids) were generated from the measured spectra; map points were interpolated for display purposes. Representative TOI maps of a breast lesion at two time points are shown with absorption spectra from normal (N) and tumor (T) regions as indicated in the TOI maps. In this example, a pathological complete response was achieved with spectra in the T region approaching those of the N region. From: Cerussi AE, Tanamai VW, Hsiang D, Butler J, Mehta RS, Tromberg BJ. Diffuse optical spectroscopic imaging correlates with final pathological response in breast cancer neoadjuvant chemotherapy. Philos Transact A Math Phys Eng Sci. 2011;369(1955):4512-30.
Current Research Goals
General research strategy for fiber-based deep tissue (> 3mm) functional imaging:
- Miniature point-of-care imaging devices using low-cost consumer electronics
- Handheld, portable broadband spectroscopic multi-channel instruments for clinical translation
- Broadband spectral tomography instruments for hyperspectral tomography
- Optical probes designed for specific tissue sites (i.e., breast, brain, muscle, endoscopy)
- Improved imaging localization by exploiting spectral, temporal and spatial information content
Bernard Choi, Ph.D.
Anthony Durkin, Ph.D.
Additional PersonnelDOSI Group
Diffuse optical imaging using spatially and temporally modulated light.
O'Sullivan TD, Cerussi AE, Cuccia DJ, Tromberg BJ.
J Biomed Opt. 2012 Jul;17(7):071311.
PMID: 22894472 [PubMed - in process]
Determination of the effect of source intensity profile on speckle contrast using coherent spatial frequency domain imaging.
Rice TB, Konecky SD, Owen C, Choi B, Tromberg BJ.
Biomed Opt Express. 2012 Jun 1;3(6):1340-9. Epub 2012 May 11.
PMID: 22741080 [PubMed] Free PMC Article
Imaging scattering orientation with spatial frequency domain imaging.
Konecky SD, Rice T, Durkin AJ, Tromberg BJ.
J Biomed Opt. 2011 Dec;16(12):126001.
PMID: 22191918 [PubMed - indexed for MEDLINE]
Spatial frequency domain imaging of port wine stain biochemical composition in response to laser therapy: A pilot study.
Mazhar A, Sharif SA, Cuccia JD, Nelson JS, Kelly KM, Durkin AJ.
Lasers Surg Med. 2012 Aug 21. doi: 10.1002/lsm.22067. [Epub ahead of print]
PMID: 22911574 [PubMed - as supplied by publisher]
Wide-field functional imaging of blood flow and hemoglobin oxygen saturation in the rodent dorsal window chamber.
Moy AJ, White SM, Indrawan ES, Lotfi J, Nudelman MJ, Costantini SJ, Agarwal N, Jia W, Kelly KM, Sorg BS, Choi B.
Microvasc Res. 2011 Nov;82(3):199-209. Epub 2011 Jul 23. Review.
PMID: 21787792 [PubMed - indexed for MEDLINE]
Baseline tumor oxygen saturation correlates with a pathologic complete response in breast cancer patients undergoing neoadjuvant chemotherapy.
Ueda S, Roblyer D, Cerussi A, Durkin A, Leproux A, Santoro Y, et al.
Cancer Res; 72(17); 4318-28.
Head-up tilt and hyperventilation produce similar changes in cerebral oxygenation and blood volume: an observational comparison study using frequency-domain near-infrared spectroscopy.
Meng L, Mantulin WW, Alexander BS, Cerussi AE, Tromberg BJ, Yu Z, et al.
Canadian Journal of Anesthesia/Journal canadien d'anesthée. 2012;59(4):357-65.
Molecular imaging of water binding state and diffusion in breast cancer using Diffuse Optical Spectroscopy and Diffusion Weighted MRI.
Chung SH, Yu H, Su M-Y, Cerussi AE, Tromberg BJ.
J Biomed Opt. 2012;17(7):071304.
Tissue phantoms in multicenter clinical trials for diffuse optical technologies.
Cerussi AE, Warren R, Hill B, Roblyer D, Leproux A, Durkin AF, et al.
Biomed Opt Express. 2012;3(5):966-71. PMCID: PMCPMC3342201.