High-Speed Time-Domain Diffuse Optical Tomography with a Sensitivity Equation-based Neural Network.

Steady progress in time-domain diffuse optical tomography (TD-DOT) technology is allowing for the first time the design of low-cost, compact, and high-performance systems, thus promising more widespread clinical TD-DOT use, such as for recording brain tissue hemodynamics. TD-DOT is known to provide more accurate values of optical properties and physiological parameters compared to its frequency-domain or steady-state counterparts. However, achieving high temporal resolution is still difficult, as solving the inverse problem is computationally demanding, leading to relatively long reconstruction times. The runtime is further compromised by processes that involve 'nontrivial' empirical tuning of reconstruction parameters, which increases complexity and inefficiency. To address these challenges, we present a new reconstruction algorithm that combines a deep-learning approach with our previously introduced sensitivity-equation-based, non-iterative sparse optical reconstruction (SENSOR) code. The new algorithm (called SENSOR-NET) unfolds the iterations of SENSOR into a deep neural network. In this way, we achieve high-resolution sparse reconstruction using only learned parameters, thus eliminating the need to tune parameters prior to reconstruction empirically. Furthermore, once trained, the reconstruction time is not dependent on the number of sources or wavelengths used. We validate our method with numerical and experimental data and show that accurate reconstructions with 1 mm spatial resolution can be obtained in under 20 milliseconds regardless of the number of sources used in the setup. This opens the door for real-time brain monitoring and other high-speed DOT applications.

Postintervention monitoring of peripheral arterial disease wound healing using dynamic vascular optical spectroscopy.

Significance: Due to the persistence of chronic wounds, a second surgical intervention is often necessary for patients with peripheral arterial disease (PAD) within a year of the first intervention. The dynamic vascular optical spectroscopy system (DVOS) may assist physicians in determining patient prognosis only a month after the first surgical intervention. Aim: We aim to assess the DVOS utility in characterizing wound healing in PAD patients after endovascular intervention. Approach: The DVOS used near-infrared light ( 670 < λ < 850 nm ) to record hemodynamic response to a cuff inflation in 14 PAD patients with lower limb ulcers immediately before, immediately after, and at a first follow-up 3 to 4 weeks after intervention. Ankle-brachial index (ABI) and arterial duplex ultrasound (A-DUS) measurements were obtained when possible. Results: The total hemoglobin plateau time differed significantly between patients with ulcers that reduced in size ( N = 9 ) and patients with ulcers that did not ( N = 5 ) 3 to 4 weeks after intervention ( p value < 0.001 ). Data correlated strongly (89% sensitivity, 100% specificity, and AUC = 0.96 ) with long-term wound healing. ABI and A-DUS measurements were not statistically associated with wound healing. Conclusions: This pilot study demonstrates the potential of the DVOS to aid physicians in giving accurate long-term wound healing prognoses 1 month after intervention.

Inhibition of calpain but not caspase activity by spectrin fragments.

Calpains and caspases are ubiquitous cysteine proteases that are associated with a variety of cellular pathways. Calpains are involved in processes such as long term potentiation, cell motility and apoptosis, and have been shown to cleave non-erythroid (brain) alpha- and beta-spectrin and erythroid beta-spectrin. The cleavage of erythroid alpha-spectrin by calpain has not been reported. Caspases play an important role in the initiation and execution of apoptosis, and have been shown to cleave non-erythroid but not erythroid spectrin. We have studied the effect of spectrin fragments on calpain and caspase activities. The erythroid and non-erythroid spectrin fragments used were from the N-terminal region of alpha-spectrin, and C-terminal region of beta-spectrin, both consisting of regions involved in spectrin tetramer formation. We observed that the all spectrin fragments exhibited a concentration-dependent inhibitory effect on calpain, but not caspase activity. It is clear that additional studies are warranted to determine the physiological significance of calpain inhibition by spectrin fragments. Our findings suggest that calpain activity is modulated by the presence of spectrin partial domains at the tetramerization site. It is not clear whether the inhibitory effect is substrate specific or is a general effect. Further studies of this inhibitory effect may lead to the identification and development of new therapeutic agents specifically for calpains, but not for caspases. Proteins/peptides with a coiled coil helical conformation should be studied for potential inhibitory effects on calpain activity.