Human retina consists of multiple layers, with oxygen supply from chorioidal and retinal vascular circulations. A number of ocular disorders are associated with insufficient oxygen supply in the retinal layer. However no effective method has been developed yet to quantify the retinal tissue oxygen saturation. Diffuse optical imaging and spectroscopy (DOIS) offers a new opportunity for tissue oximetry. The technique is non-invasive, low cost, non-radioactive and real time. However, the application of DOIS in ocular imaging is hindered by the following limitations: 1) lack of spatial and depth resolution; 2) light transportation in thin layers less than single mean free path; 3) low scattering coefficient in neural retina and high absorption coefficient in RPE; 4) interference by retinal vessels. This paper discussed both theoretical and experimental works toward quantitative assessment of retinal tissue oxygenation. Theoretical side, photon migration in multi-layer tissue was simulated by solving diffusion equations in Fourier domain. The resulting diffuse reflectance was compared with Monte Carlo simulation. Experimental side, a dual modal imaging prototype was developed combining white light interferometry for tissue thickness measurement and near infrared spectroscopy for optical property measurement. The capability for white light interfferometry to capture thin layer thickness was demonstrated by a series of benchtop tests.
We proposed a dynamic near infrared/ultrasound dual modal imaging system (dNIRUS) for characterizing suspicious breast lesions non-invasively. dNIRUS measures the change of tissue mechanical and physiologic parameters in response to dynamic stimuli such as cyclic mechanical compression. It integrates near infrared imaging of tumor physiologic properties, ultrasound imaging of tumor deformation/displacement, and real time pressure monitoring under a designated cyclic compression load. The concept of dNIRUS was quantitatively verified on multi-layer tissue simulating phantoms under cyclic compression. A lumped visco-elastic model was used to characterize the phantom mechanical properties and to simulate the tissue deformation. The diffusion equations were solved analytically in Fourier domain with the moving boundary. The theoretical models were verified by a series of bench top tests where a sensor head integrating an ultrasound probe and a near infrared probe was installed on a load frame. A cyclic compression force was applied to a two-layer tissue simulating phantom. Phantom displacement, compressive pressure and diffuse optical reflectance were recorded simultaneously. Deformation of each layer of the phantom was reconstructed from ultrasound images and was consistent with the load frame measurements as well as the theoretical predictions. Diffuse reflectance amplitude showed corresponding fluctuation during compression, while the phase did not change significantly at the oscillation frequency of 0.5Hz. Further work is necessary to develop forward and inverse algorithms for dynamic characterization of suspicious breast lesions.
For characterization of suspicious breast lesions, we used a dual modal imaging scheme integrating a hand-held near infrared imager and a portable ultrasound probe. The functional properties of the suspicious lesion and the surrounding tissue were reconstructed based on the diffuse reflectance measurement of the near infrared light and the ultrasound measurement of the tumor morphology. The near infrared/ultrasound dual modal imaging system has been validated through a series of bench top tests where tumor simulators with various absorptions were embedded at different depth in a liquid tissue-simulating phantom. The clinical trial of the imaging scheme was conducted on 44 subjects with suspicious breast lesions identified by mammography and/or ultrasound. Both near infrared and ultrasound data were collected from the area of the suspicious breast lesion and from the adjacent reference breast tissue. The clinical trial demonstrates that the dual modal imaging system can reach up to 71% of diagnostic sensitivity and 58% of specificity in detecting breast carcinoma. This may indicate that the system could potentially be used in breast cancer detection adjunctive with mammography.
Recent advances in diffuse optical imaging and spectroscopy (DOIS) allow the noninvasive measurement of local changes in cerebral oxygenation and hemodynamics. Available DOIS devices fall into three categories: time domain (TD), frequency domain (FD) and continuous wave (CW). The TD and FD devices have potential for high spatial resolution, high temporal resolution and high accuracy measurement, but the instrument cost and the hardware size prevent their wide clinical application. Furthermore, the presence of the low scattering cerebrospinal fluid layer (CSF) and its thickness variation during motion challenges quantitative, continuous monitoring of the cortex layer oxygenation and blood content. MRI has been used to provide a priori knowledge of the head anatomy that helps the NIR image reconstruction. However, the technology is expensive and lacks portability. This paper proposes a method that combines the accuracy of a TD/FD system and the portability of a CW device. With the optical baseline measured by a TD or FD device and the layer thickness characterized by an ultrasound transducer, a conventional CW system may be able to quantify the cortex layer optical absorption with high accuracy. In this paper, the feasibility of using ultrasound guided CW spectroscopy to monitor brain activities was studied on a multi layer head model using Monte Carlo simulation and order of magnitude analysis. A forward algorithm based on diffuse approximation and 2D Fourier Transform was used to optimize the source detector separation. Both analytical and neuron network approaches were developed for inverse calculation of the cortex layer absorption in real time. An ultrasound transducer was used to monitor the thickness of different layers surrounding the cerebral cortex. The concept of ultrasound guided CW spectroscopy was demonstrated by numerical simulation on a 2 layer head model and the use of the ultrasound transducer for layer thickness characterization was verified by animal and bench top results.
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