Imaging of tissue blood flow (BF) distributions provides vital information for the diagnosis and therapeutic monitoring of various vascular diseases. The innovative near-infrared speckle contrast diffuse correlation tomography (scDCT) technique produces full 3D BF distributions. Many advanced features are provided over competing technologies including high sampling density, fast data acquisition, noninvasiveness, noncontact, affordability, portability, and translatability across varied subject sizes. The basic principle, instrumentation, and data analysis algorithms are presented in detail. The extensive applications are summarized such as imaging of cerebral BF (CBF) in mice, rat, and piglet animals with skull penetration into deep brain. Clinical human testing results are described by recovery of BF distributions on preterm infants (CBF) through incubator wall, and on sensitive burn tissues and mastectomy skin flaps without direct device-tissue interactions. Supporting activities outlined include integrated capability for acquiring surface curvature information, rapid 2D blood flow mapping, and optimizations via tissue-like phantoms and computer simulations. These applications and activities both highlight and guide the reader as to the expected abilities and limitations of scDCT for adapting into their own preclinical/clinical research, use in constrained environments (i.e., neonatal intensive care unit bedside), and use on vulnerable subjects and measurement sites.

"Imaging of tissue blood flow (BF) distributions provides vital information for the diagnosis and therapeutic monitoring of various vascular diseases. The innovative near-infrared speckle contrast diffuse correlation tomography (scDCT) technique produces full 3D BF distributions. Many advanced features are provided over competing technologies including high sampling density, fast data acquisition, noninvasiveness, noncontact, affordability, portability, and translatability across varied subject sizes. The basic principle, instrumentation, and data analysis algorithms are presented in detail. The extensive applications are summarized such as imaging of cerebral BF (CBF) in mice, rat, and piglet animals with skull penetration into deep brain. Clinical human testing results are described by recovery of BF distributions on preterm infants (CBF) through incubator wall, and on sensitive burn tissues and mastectomy skin flaps without direct device-tissue interactions. Supporting activities outlined include integrated capability for acquiring surface curvature information, rapid 2D blood flow mapping, and optimizations via tissue-like phantoms and computer simulations. These applications and activities both highlight and guide the reader as to the expected abilities and limitations of scDCT for adapting into their own preclinical/clinical research, use in constrained environments (i.e., neonatal intensive care unit bedside), and use on vulnerable subjects and measurement sites"--

Imaging of tissue blood flow (BF) distributions provides vital information for the diagnosis and therapeutic monitoring of various vascular diseases. The innovative near-infrared speckle contrast diffuse correlation tomography (scDCT) technique produces full 3D BF distributions. Many advanced features are provided over competing technologies including high sampling density, fast data acquisition, noninvasiveness, noncontact, affordability, portability, and translatability across varied subject sizes. The basic principle, instrumentation, and data analysis algorithms are presented in detail. The extensive applications are summarized such as imaging of cerebral BF (CBF) in mice, rat, and piglet animals with skull penetration into deep brain. Clinical human testing results are described by recovery of BF distributions on preterm infants (CBF) through incubator wall, and on sensitive burn tissues and mastectomy skin flaps without direct device-tissue interactions. Supporting activities outlined include integrated capability for acquiring surface curvature information, rapid 2D blood flow mapping, and optimizations via tissue-like phantoms and computer simulations. These applications and activities both highlight and guide the reader as to the expected abilities and limitations of scDCT for adapting into their own preclinical/clinical research, use in constrained environments (i.e., neonatal intensive care unit bedside), and use on vulnerable subjects and measurement sites.

Jöbsis was the first to describe the in vivo application of near-infrared spectroscopy (NIRS), also called diffuse optical spectroscopy (DOS). NIRS was originally designed for the clinical monitoring of tissue oxygenation, and today it has also become a useful tool for neuroimaging studies (functional near-infrared spectroscopy, fNIRS). However, difficulties in the selective and quantitative measurements of tissue hemoglobin (Hb), which have been central in the NIRS field for over 40 years, remain to be solved. To overcome these problems, time-domain (TD) and frequency-domain (FD) measurements have been tried. Presently, a wide range of NIRS instruments are available, including commonly available commercial instruments for continuous wave (CW) measurements, based on the modified Beer–Lambert law (steady-state domain measurements). Among these measurements, the TD measurement is the most promising approach, although compared with CW and FD measurements, TD measurements are less common, due to the need for large and expensive instruments with poor temporal resolution and limited dynamic range. However, thanks to technological developments, TD measurements are increasingly being used in research, and also in various clinical settings. This Special Issue highlights issues at the cutting edge of TD DOS and diffuse optical tomography (DOT). It covers all aspects related to TD measurements, including advances in hardware, methodology, the theory of light propagation, and clinical applications.

The non-invasive and, often, continuous measurement of the hemodynamics of the body, and for the main purposes of this thesis, the brain, is desired because both the instantaneous values and their changes over time constantly adapt to the conditions affecting the body and its environment. They are altered in pathological situations and in response to increased function. It is desirable for these measurements to be continuous, reliable, minimally invasive, and relatively inexpensive. In recent years, optical techniques that, by using diffusing and deep-reaching (up to few centimeters) light at skin-safe levels of intensity, combine the aforementioned characteristics, have increasingly become used in clinical and research settings. However, to date there is, on one side the need to expand the number and scope of translational studies, and, on the other, to address shortcomings like the contamination of signals from unwanted tissue volumes (partial volume effects). A further important goal is to increase the depth of penetration of light without affecting the non-invasive nature of diffuse optics.My PhD was aimed at several aspects of this problem; (i) the development of new, more advanced methods, i.e. the time/pathlength resolved, to improve the differentiation between superficial and deeper tissues layers, (ii) the exploration of new application areas, i.e. to characterize the microvascular status of bones, to study the functional response of the baby brain, and (iii) to improve the quality control of the systems , i.e. by introducing a long shelf-life dynamic phantom.In conceptual order, first I introduce long shelf-life reference standards for diffuse correlation spectroscopy. Secondly, I describe the use of an existing hybrid time domain and diffuse correlation spectroscopy system to monitor the changes that some pathological conditions, in this case osteoporosis and human immunodeficiency virus infection, may have on many aspects of the human bone tissue that are currently not easy to measure (i.e. invasively assessed) by conventional techniques. Thirdly, I describe the development of a novel time domain optical technique that intimately combines, introducing many previously unmet advancements, the two previously cited optical spectroscopy techniques. For the first time I was able to produce a time domain device and protocol that can monitor the blood flow in vivo in the head and muscles of healthy humans. Lastly, I describe a device and method that I have used to monitor changes in blood flow in healthy human infants of three to five months of age, for the first time in this age bracket, as a marker of activation following visual stimulation. Overall, this work pushes the limit of the technology that makes use of diffuse light to minimally invasively, continuously, and reliably monitor endogenous markers of pathological and physiological processes in the human body.

Diffuse Optical Tomography has drawn more and more interests in the biomedical field over the recent couple of decades due to its ability to noninvasively recover not only tissue structural information but also functional and molecular properties. The contrasts that optical parameters could demonstrate in DOT are usually higher than those of the conventional methods. Based on these contrasts, different approaches had been developed applying DOT for imaging, and so far lots of efforts were spent on detecting breast cancer by imaging tissue absorption and scattering coefficients as well as hemoglobin concentration and oxygen saturation level. In this work, we tried to expand the ability of DOT in breast cancer detection by introducing Phase-contrast diffuse optical tomography (PCDOT). PCDOT uses near-infrared diffusing light to non-invasively reconstruct tissue refractive index (RI) distribution. RI depends on the tissue's physical and chemical properties and previous study revealed that it might serve as a promising imaging parameter in breast cancer detection. We've first developed a 2-step method to improve the PCDOT image both qualitatively and quantitatively at single-wavelength; then we've introduced a multispectral PCDOT algorithm to more efficiently reconstruct RI simultaneously with other tissue functional parameters and attempted to improve this algorithm by different structural regularization methods.