Mohammed Rahman

Low-cost, multimodal, portable screening system for early detection of oral cancer

Oral cancer is an important global health problem. There is an urgent need for improved methods to detect oral cancer and its precursors, because early detection is the best way to reduce oral cancer mortality and morbidity. In this work, we describe simple modifications to a surgical headlight system that enables direct visualization and digital image acquisition from oral tissue in multiple imaging modalities including fluorescence, white-light reflectance, and orthogonal polarization reflectance. Images obtained with the system in-vivo demonstrate that it is an attractive technology to explore for oral cancer screening in low-resource environments where clinical expertise is often unavailable.

Evaluation of a low-cost, portable imaging system for early detection of oral cancer

BackgroundThere is an important global need to improve early detection of oral cancer. Recent reports suggest that optical imaging technologies can aid in the identification of neoplastic lesions in the oral cavity; however, there is little data evaluating the use of optical imaging modalities in resource limited settings where oral cancer impacts patients disproportionately. In this article, we evaluate a simple, low-cost optical imaging system that is designed for early detection of oral cancer in resource limited settings. We report results of a clinical study conducted at Tata Memorial Hospital (TMH) in Mumbai, India using this system as a tool to improve detection of oral cancer and its precursors.MethodsReflectance images with white light illumination and fluorescence images with 455 nm excitation were obtained from 261 sites in the oral cavity from 76 patients and 90 sites in the oral cavity from 33 normal volunteers. Quantitative image features were used to develop classification algorithms to identify neoplastic tissue, using clinical diagnosis of expert observers as the gold standard.ResultsUsing the ratio of red to green autofluorescence, the algorithm identified tissues judged clinically to be cancer or clinically suspicious for neoplasia with a sensitivity of 90% and a specificity of 87%.ConclusionsResults suggest that the performance of this simple, objective low-cost system has potential to improve oral screening efforts, especially in low-resource settings.

High resolution, molecular-specific, reflectance imaging in optically dense tissue phantoms with structured-illumination

Structured-illumination microscopy delivers confocal-imaging capabilities and may be used for optical sectioning in bio-imaging applications. However, previous structured-illumination implementations are not capable of imaging molecular changes within highly scattering, biological samples in reflectance mode. Here, we present two advances which enable successful structured illumination reflectance microscopy to image molecular changes in epithelial tissue phantoms. First, we present the sine approximation algorithm to improve the ability to reconstruct the in-focus plane when the out-of-focus light is much greater in magnitude. We characterize the dependencies of this algorithm on phase step error, random noise and backscattered out-of-focus contributions. Second, we utilize a molecular-specific reflectance contrast agent based on gold nanoparticles to label disease-related biomarkers and increase the signal and signal-to-noise ratio (SNR) in structured illumination microscopy of biological tissue. Imaging results for multi-layer epithelial cell phantoms with optical properties characteristic of normal and cancerous tissue labeled with nanoparticles targeted against the epidermal growth factor receptor (EGFR) are presented. Structured illumination images reconstructed with the sine approximation algorithm compare favorably to those obtained with a standard confocal microscope; this new technique can be implemented in simple and small imaging platforms for future clinical studies.

Imaging performance of a miniature integrated microendoscope

An integrated miniature multi-modal microscope (4M device) for microendoscopy was built and tested. Imaging performance is evaluated and imaging results are presented for both fluorescence and reflectance samples. Images of biological samples show successful imaging of both thin layers of fixed cells prepared on a slide as well as thick samples of excised fixed porcine epithelial tissue, thus demonstrating the potential for in vivo use.

Multi-modal miniature microscope: 4M Device for bio-imaging applications - an overview of the system

The multi-modal miniature microscope (4M) device to image morphology and cytochemistry in vivo is a microscope on a chip including optical, micro-mechanical, and electronic components. This paper describes all major system components: optical system, custom high speed CMOS detector and comb drive actuator. The hybrid sol-gel lenses, their fabrication and assembling technology, optical system parameters, and various operation modes (fluorescence, reflectance, structured illumination) are also discussed. A particularly interesting method is a structured illumination technique that delivers confocal-imaging capabilities and may be used for optical sectioning. For reconstruction of the sectioned layer a sine approximation algorithm is applied. Structured illumination is produced with LIGA fabricated actuator scanning in resonance. The spatial resolution of the system is 1 μm, and was magnified by 4x matching the CMOS pixel size of 4 μm (a lateral magnification is 4:1), and the extent of field of the system is 250μm. An overview of the 4M device is combined with the presentation of imaging results for epithelial cell phantoms with optical properties characteristic of normal and cancerous tissue labeled with nanoparticles.

Multi-modal miniaturized microscope: successful merger of optical, MEMS, and electronic technologies

The multi-modal miniature microscope (4M) device for early cancer detection is based on micro-optical table (MOT) platform which accommodates on a chip: optical, micro-mechanical, and electronic components. The MOT is a zeroalignment optical-system concept developed for a wide variety of opto-mechanical instruments. In practical terms this concept translates into assembly errors that are smaller than the tolerances on the performance of the optical system. This paper discusses all major system elements: optical system, custom high speed CMOS detector and comb drive actuator. It also points to mutual relations between different technologies. The hybrid sol-gel lenses, their fabrication and assembling techniques, optical system parameters, and various operation modes are also discussed. A particularly interesting mode is a structured illumination technique that delivers confocal-imaging capabilities and may be used for optical sectioning. Structured illumination is produced with LIGA fabricated actuator scanning in resonance and reconstructed using sine approximation algorithm.

Low-cost, portable imaging systems for cancer detection

Worldwide incidence and mortality rates due to cancer continue to rise, with the burden of disease increasingly shifting to developing countries. Several optical diagnostic methods are under development to enable earlier detection of cancer, however, these are primarily intended for use in healthcare facilities in industrialized countries. Using knowledge gained from early clinical studies with large-scale prototype systems, we have designed and tested low-cost, portable versions of these instruments. We propose that these systems may be used for early diagnosis and screening in developing countries, and that pilot clinical studies are warranted in these low-resource settings.

Thick Tissue Imaging with the Multi-Modal Miniaturized Microscope 4M Device

This paper presents the multi-modal miniature microscope (4M) device for pre-cancer detection.Recent progress has affected all major system components including optics, micro-mechanics, and electronics.Results of imaging thick tissue phantoms using epi-illumination mode and structured illumination mode are presented and discussed.