Luma V. Halig

Hyperspectral imaging and quantitative analysis for prostate cancer detection

Hyperspectral imaging (HSI) is an emerging modality for various medical applications. Its spectroscopic data might be able to be used to noninvasively detect cancer. Quantitative analysis is often necessary in order to differentiate healthy from diseased tissue. We propose the use of an advanced image processing and classification method in order to analyze hyperspectral image data for prostate cancer detection. The spectral signatures were extracted and evaluated in both cancerous and normal tissue. Least squares support vector machines were developed and evaluated for classifying hyperspectral data in order to enhance the detection of cancer tissue. This method was used to detect prostate cancer in tumor-bearing mice and on pathology slides. Spatially resolved images were created to highlight the differences of the reflectance properties of cancer versus those of normal tissue. Preliminary results with 11 mice showed that the sensitivity and specificity of the hyperspectral image classification method are 92.8% to 2.0% and 96.9% to 1.3%, respectively. Therefore, this imaging method may be able to help physicians to dissect malignant regions with a safe margin and to evaluate the tumor bed after resection. This pilot study may lead to advances in the optical diagnosis of prostate cancer using HSI technology.

Targeted iron-oxide nanoparticle for photodynamic therapy and imaging of head and neck cancer.

Photodynamic therapy (PDT) is a highly specific anticancer treatment modality for various cancers, particularly for recurrent cancers that no longer respond to conventional anticancer therapies. PDT has been under development for decades, but light-associated toxicity limits its clinical applications. To reduce the toxicity of PDT, we recently developed a targeted nanoparticle (NP) platform that combines a second-generation PDT drug, Pc 4, with a cancer targeting ligand, and iron oxide (IO) NPs. Carboxyl functionalized IO NPs were first conjugated with a fibronectin-mimetic peptide (Fmp), which binds integrin β1. Then the PDT drug Pc 4 was successfully encapsulated into the ligand-conjugated IO NPs to generate Fmp-IO-Pc 4. Our study indicated that both nontargeted IO-Pc 4 and targeted Fmp-IO-Pc 4 NPs accumulated in xenograft tumors with higher concentrations than nonformulated Pc 4. As expected, both IO-Pc 4 and Fmp-IO-Pc 4 reduced the size of HNSCC xenograft tumors more effectively than free Pc 4. Using a 10-fold lower dose of Pc 4 than that reported in the literature, the targeted Fmp-IO-Pc 4 NPs demonstrated significantly greater inhibition of tumor growth than nontargeted IO-Pc 4 NPs. These results suggest that the delivery of a PDT agent Pc 4 by IO NPs can enhance treatment efficacy and reduce PDT drug dose. The targeted IO-Pc 4 NPs have great potential to serve as both a magnetic resonance imaging (MRI) agent and PDT drug in the clinic.

Spectral-spatial classification for noninvasive cancer detection using hyperspectral imaging

Abstract. Early detection of malignant lesions could improve both survival and quality of life of cancer patients. Hyperspectral imaging (HSI) has emerged as a powerful tool for noninvasive cancer detection and diagnosis, with the advantage of avoiding tissue biopsy and providing diagnostic signatures without the need of a contrast agent in real time. We developed a spectral-spatial classification method to distinguish cancer from normal tissue on hyperspectral images. We acquire hyperspectral reflectance images from 450 to 900 nm with a 2-nm increment from tumor-bearing mice. In our animal experiments, the HSI and classification method achieved a sensitivity of 93.7% and a specificity of 91.3%. The preliminary study demonstrated that HSI has the potential to be applied in vivo for noninvasive detection of tumors.

Detection of Cancer Metastasis Using a Novel Macroscopic Hyperspectral Method

The proposed macroscopic optical histopathology includes a broad-band light source which is selected to illuminate the tissue glass slide of suspicious pathology, and a hyperspectral camera that captures all wavelength bands from 450 to 950 nm. The system has been trained to classify each histologic slide based on predetermined pathology with light having a wavelength within a predetermined range of wavelengths. This technology is able to capture both the spatial and spectral data of tissue. Highly metastatic human head and neck cancer cells were transplanted to nude mice. After 2- 3 weeks, the mice were euthanized and the lymph nodes and lung tissues were sent to pathology. The metastatic cancer is studied in lymph nodes and lungs. The pathological slides were imaged using the hyperspectral camera. The results of the proposed method were compared to the pathologic report. Using hyperspectral images, a library of spectral signatures for different tissues was created. The high-dimensional data were classified using a support vector machine (SVM). The spectra are extracted in cancerous and non-cancerous tissues in lymph nodes and lung tissues. The spectral dimension is used as the input of SVM. Twelve glasses are employed for training and evaluation. The leave-one-out cross-validation method is used in the study. After training, the proposed SVM method can detect the metastatic cancer in lung histologic slides with the specificity of 97.7% and the sensitivity of 92.6%, and in lymph node slides with the specificity of 98.3% and the sensitivity of 96.2%. This method may be able to help pathologists to evaluate many histologic slides in a short time.

3D Segmentation of Prostate Ultrasound images Using Wavelet Transform.

The current definitive diagnosis of prostate cancer is transrectal ultrasound (TRUS) guided biopsy. However, the current procedure is limited by using 2D biopsy tools to target 3D biopsy locations. This paper presents a new method for automatic segmentation of the prostate in three-dimensional transrectal ultrasound images, by extracting texture features and by statistically matching geometrical shape of the prostate. A set of Wavelet-based support vector machines (WSVMs) are located and trained at different regions of the prostate surface. The WSVMs capture texture priors of ultrasound images for classification of the prostate and non-prostate tissues in different zones around the prostate boundary. In the segmentation procedure, these W-SVMs are trained in three sagittal, coronal, and transverse planes. The pre-trained W-SVMs are employed to tentatively label each voxel around the surface of the model as a prostate or non-prostate voxel by the texture matching. The labeled voxels in three planes after post-processing is overlaid on a prostate probability model. The probability prostate model is created using 10 segmented prostate data. Consequently, each voxel has four labels: sagittal, coronal, and transverse planes and one probability label. By defining a weight function for each labeling in each region, each voxel is labeled as a prostate or non-prostate voxel. Experimental results by using real patient data show the good performance of the proposed model in segmenting the prostate from ultrasound images.

Framework for hyperspectral image processing and quantification for cancer detection during animal tumor surgery

Abstract. Hyperspectral imaging (HSI) is an imaging modality that holds strong potential for rapid cancer detection during image-guided surgery. But the data from HSI often needs to be processed appropriately in order to extract the maximum useful information that differentiates cancer from normal tissue. We proposed a framework for hyperspectral image processing and quantification, which includes a set of steps including image preprocessing, glare removal, feature extraction, and ultimately image classification. The framework has been tested on images from mice with head and neck cancer, using spectra from 450- to 900-nm wavelength. The image analysis computed Fourier coefficients, normalized reflectance, mean, and spectral derivatives for improved accuracy. The experimental results demonstrated the feasibility of the hyperspectral image processing and quantification framework for cancer detection during animal tumor surgery, in a challenging setting where sensitivity can be low due to a modest number of features present, but potential for fast image classification can be high. This HSI approach may have potential application in tumor margin assessment during image-guided surgery, where speed of assessment may be the dominant factor.

3D Non-rigid Registration Using Surface and Local Salient Features for Transrectal Ultrasound Image-guided Prostate Biopsy

We present a 3D non-rigid registration algorithm for the potential use in combining PET/CT and transrectal ultrasound (TRUS) images for targeted prostate biopsy. Our registration is a hybrid approach that simultaneously optimizes the similarities from point-based registration and volume matching methods. The 3D registration is obtained by minimizing the distances of corresponding points at the surface and within the prostate and by maximizing the overlap ratio of the bladder neck on both images. The hybrid approach not only capture deformation at the prostate surface and internal landmarks but also the deformation at the bladder neck regions. The registration uses a soft assignment and deterministic annealing process. The correspondences are iteratively established in a fuzzy-to-deterministic approach. B-splines are used to generate a smooth non-rigid spatial transformation. In this study, we tested our registration with pre- and postbiopsy TRUS images of the same patients. Registration accuracy is evaluated using manual defined anatomic landmarks, i.e. calcification. The root-mean-squared (RMS) of the difference image between the reference and floating images was decreased by 62.6±9.1% after registration. The mean target registration error (TRE) was 0.88±0.16 mm, i.e. less than 3 voxels with a voxel size of 0.38×0.38×0.38 mm3 for all five patients. The experimental results demonstrate the robustness and accuracy of the 3D non-rigid registration algorithm.

Hyperspectral Imaging for Cancer Surgical Margin Delineation: Registration of Hyperspectral and Histological Images

The determination of tumor margins during surgical resection remains a challenging task. A complete removal of malignant tissue and conservation of healthy tissue is important for the preservation of organ function, patient satisfaction, and quality of life. Visual inspection and palpation is not sufficient for discriminating between malignant and normal tissue types. Hyperspectral imaging (HSI) technology has the potential to noninvasively delineate surgical tumor margin and can be used as an intra-operative visual aid tool. Since histological images provide the ground truth of cancer margins, it is necessary to warp the cancer regions in ex vivo histological images back to in vivo hyperspectral images in order to validate the tumor margins detected by HSI and to optimize the imaging parameters. In this paper, principal component analysis (PCA) is utilized to extract the principle component bands of the HSI images, which is then used to register HSI images with the corresponding histological image. Affine registration is chosen to model the global transformation. A B-spline free form deformation (FFD) method is used to model the local non-rigid deformation. Registration experiment was performed on animal hyperspectral and histological images. Experimental results from animals demonstrated the feasibility of the hyperspectral imaging method for cancer margin detection.

Hyperspectral imaging and spectral-spatial classification for cancer detection

Hyperspectral imaging is an emerging technology for biomedical applications. In this study, an advanced image processing and classification method is proposed to analyze hyperspectral image data for prostate cancer detection. Least squares support vector machines (LS-SVMs) were developed and evaluated for classifying hyperspectral data in order to enhance the detection of cancer tissue. The method was used to detect prostate cancer in tumor-bearing mice. Spatially resolved images were created to highlight the differences of the reflectance properties of cancer versus those of normal tissue. Preliminary results in mice show that the hyperspectral imaging and classification method was able to reliably detect prostate tumors in the animal model. The hyperspectral imaging technique may provide a new tool for optical diagnosis of cancer.

Spectral-spatial classification using tensor modeling for cancer detection with hyperspectral imaging

As an emerging technology, hyperspectral imaging (HSI) combines both the chemical specificity of spectroscopy and the spatial resolution of imaging, which may provide a non-invasive tool for cancer detection and diagnosis. Early detection of malignant lesions could improve both survival and quality of life of cancer patients. In this paper, we introduce a tensor-based computation and modeling framework for the analysis of hyperspectral images to detect head and neck cancer. The proposed classification method can distinguish between malignant tissue and healthy tissue with an average sensitivity of 96.97% and an average specificity of 91.42% in tumor-bearing mice. The hyperspectral imaging and classification technology has been demonstrated in animal models and can have many potential applications in cancer research and management.