Near infrared spectroscopy (NIRS) is an emerging functional brain imaging tool capable of assessing cerebral concentrations of oxygenated hemoglobin (HbO) and deoxygenated hemoglobin (HbR) during brain activation noninvasively. As an extension of NIRS, diffuse optical tomography (DOT) not only shares the merits of providing continuous readings of cerebral oxygenation, but also has the ability to provide spatial resolution in the millimeter scale. Based on the scattering and absorption properties of nonionizing near-infrared light in biological tissue, DOT has been successfully applied in the imaging of breast tumors, osteoarthritis and cortex activations. Here, we present a state-of-art fast high density DOT system suitable for brain imaging. It can achieve up to a 21 Hz sampling rate for a full set of two-wavelength data for 3-D DOT brain image reconstruction. The system was validated using tissue-mimicking brain-model phantom. Then, experiments on healthy subjects were conducted to demonstrate the capability of the system.
In epilepsy it has been challenging to detect early changes in brain activity that occurs prior to seizure onset and to map their origin and evolution for possible intervention. Besides, preclinical seizure experiments need to be conducted in awake animals with images reconstructed and displayed in real-time. We demonstrate using a rat model of generalized epilepsy that diffuse optical tomography (DOT) provides a unique functional neuroimaging modality for noninvasively and continuously tracking brain activities with high spatiotemporal resolution. We developed methods to conduct seizure experiments in fully awake rats using a subject-specific helmet and a restraining mechanism. For the first time, we detected early hemodynamic responses with heterogeneous patterns several minutes preceding the electroencephalographic seizure onset, supporting the presence of a “pre-seizure” state both in anesthetized and awake rats. Using a novel time-series analysis of scattering images, we show that the analysis of scattered diffuse light is a sensitive and reliable modality for detecting changes in neural activity associated with generalized seizure. We found widespread hemodynamic changes evolving from local regions of the bilateral cortex and thalamus to the entire brain, indicating that the onset of generalized seizures may originate locally rather than diffusely. Together, these findings suggest DOT represents a powerful tool for mapping early seizure onset and propagation pathways.
We describe a multispectral continuous-wave diffuse optical tomography (DOT) system that can be used for in vivo three-dimensional (3-D) imaging of seizure dynamics. Fast 3-D data acquisition is realized through a time multiplexing approach based on a parallel lighting configuration - our system can achieve 0.12ms per source per wavelength and up to 14Hz sampling rate for a full set of data for 3-D DOT image reconstruction. The system is validated using both static and dynamic tissue-like phantoms. In vivo rat experiments using both focal and generalized models of seizure are also demonstrated. In the focal seizure experiment, hemodynamic seizure focus was clearly detected and tracked. In the generalized seizure experiment, early hemodynamic responses with heterogeneous patterns were detected several minutes preceding the EEG onset of seizures and widespread hemodynamic changes were found evolving from local regions. Connectivity changes were also found during the development of seizures. This study demonstrates that DOT represents a powerful tool for investigating seizure generation and propagation, elucidating the causes and mechanism of seizures.