## 4 Cutting Edge Time Domain Diffuse Optical Spectroscopy and Imaging  
This Special Issue highlights the issues at the cutting edge of TD DOS and DOT. It covers all aspects related to TD measurements described above, including advances in hardware, methodology, theory of light propagation, and clinical applications. The Special Issue has two reviews and 10 original research papers. One review paper by [PERSON], [PERSON] and [PERSON] provides a comprehensive review of the past and current status of TD DOS and TD DOT, with chronological summaries of the major events in instrument and theoretical method developments [14]. This paper will help readers who are new to NIRS and also experts to obtain an overview of TD measurements and broaden their knowledge and understanding. The second review is by [PERSON] and [PERSON] and focuses on clinical applications in brain monitoring, where they also describe recent developments in instrumentation and methodologies that have the potential to affect and broaden the clinical use of TD measurements [15]. Five of 10 original papers deal with clinical applications that utilize the strengths of TD measurements. [PERSON] and [PERSON] applied TD DOS to three studies on breast cancer, reporting the detection rate of breast cancer, tumor hemodynamic responses to neoadjuvant chemotherapy, and antiangiogenic therapy [16]. [PERSON] et al., who measured skeletal muscle oxygenation in the lower extremities during 3 h of continuous sitting, report that compression stockings suppress increases in extracellular water in the lower extremities, leading to reduced blood volume and oxygenation levels in skeletal muscles [17]. The study by [PERSON] et al. measured cerebral blood volume and optical properties in five term neonates from 2-3 min to 15 min after birth, and demonstrate that TD DOS can stably measure the cerebral hemodynamics of neonates in the labor room [18]. [PERSON] et al. examined the effects of aging, cognitive dysfunction, and brain atrophy on Hb concentrations and optical pathlengths at rest in the prefrontal cortex in 202 elderly subjects, concluding that TD DOS enables an evaluation of the relation between prefrontal oxygenation at rest and cognitive function [19]. [PERSON] et al. employed TD DOS to test their hypothesis that total Hb concentration in abdominal subcutaneous adipose tissue correlates negatively with risk factors for developing metabolic diseases and were able to verify the hypothesis [20]. [PERSON] et al. conducted basic research into the application of TD measurements to breast cancer, and report that the validity of TD DOS measurements of the lipid and water contents of the breast is confirmed by a comparison of the TD DOS values to the values measured by dual-energy computed tomography [21]. The paper by [PERSON] et al. deals with hardware, a TD fast gated NIRS system, and presents results showing that the gating approach can improve the contrast and contrast-noise ratio for the detection of absorption changes, irrespective of the source-detector separation distance [22]. Three papers present theoretical studies. To recover the optical properties from boundary measurements, iterative inversion schemes, where a theoretical TPSF is derived from the analytical solution to the PDE and fitted to the measured temporal profile of detected light intensity, are often used [23]. However, in these schemes, the initial guesses need to be close to the true values. [PERSON] et al. propose a scheme combining Markov chain Monte Carlo and iterative methods to overcome thisweakness in iterative schemes [24]. In TD DOT, regarding the datatypes obtained from the TPSF, such as temporal windows and Fourier transformations, determining which datatypes are used for image reconstruction is crucial for computational efficiency as well as for image quality. [PERSON] et al.