Sandeep Manhas

Polarimetric imaging of uterine cervix: a case study

We present a preliminary investigation of macroscopic polarimetric imaging of uterine cervix. Orthogonal state contrast (OSC) images of healthy and anomalous cervices have been taken in vivo at 550 nm. Four ex vivo cervix samples have been studied in full Muller polarimetry, at 550 nm and 700 nm, and characterized in detail by standard pathology. One sample was totally healthy, another one carried CIN lesions at very early stage (CIN1) in its visible exocervical region, while for the other two samples more advanced (CIN3) lesions were present, together with visible glandular epithelium (ectropion). Significant birefringence has been observed in the healthy regions of all six samples, both in vivo and ex vivo. Standard treatments of the Mueller images of the ex vivo samples allowed to quantify both retardation and depolarization. Retardation reached 60° in healthy regions, and disappeared in the anomalous regions of the other three ex vivo samples. The depolarization power was largest in healthy regions, and lower in CINs and ectropion. Possible origins of the observed effects are briefly discussed.

Multispectral Mueller polarimetric imaging detecting residual cancer and cancer regression after neoadjuvant treatment for colorectal carcinomas

Abstract. This work is devoted to a first exploration of Mueller polarimetric imaging for the detection of residual cancer after neoadjuvant treatment for the rectum. Three samples of colorectal carcinomas treated by radiochemotherapy together with one untreated sample are analyzed ex vivo before fixation in formalin by using a multispectral Mueller polarimetric imaging system operated from 500 to 700 nm. The Mueller images, analyzed using the Lu-Chipmann decomposition, show negligible diattenuation and retardation. The nonirradiated rectum exhibits a variation of depolarization with cancer evolution stage. At all wavelengths on irradiated samples, the contrast between the footprint of the initial tumor and surrounding healthy tissue is found to be much smaller for complete tumor regression than when a residual tumor is present, even at volume fractions of the order of 5%. This high sensitivity is attributed to the modification of stromal collagen induced by the cancer. The depolarization contrast between treated cancer and healthy tissue is found to increase monotonously with the volume fraction of residual cancer in the red part of the spectrum. Polarimetric imaging is a promising technique for detecting short-time small residual cancers, which is valuable information for pathological diagnosis and patient management by clinicians.

Ex vivo photometric and polarimetric multilayer characterization of human healthy colon by multispectral Mueller imaging

Healthy human colon samples were analyzed ex vivo with a multispectral imaging Mueller polarimeter operating from 500 to 700 nm in a backscattering configuration with diffuse light illumination impinging on the innermost tissue layer, the mucosa. The intensity and polarimetric responses were taken on whole tissues first and after progressive exfoliation of the outer layers afterwards. Moreover, these measurements were carried out with two different substrates (one bright and the other dark) successively placed beneath each sample, allowing a reasonably accurate evaluation of the contributions to the overall backscattered light by the various layers. For the shorter investigated wavelengths (500 to 550 nm) the major contribution comes from mucosa and submucosa, while for the longer wavelengths (650 to 700 nm) muscular tissue and fat also contribute significantly. The depolarization has also been studied and is found to be stronger in the red part of the spectrum, mainly due to the highly depolarizing power of the muscular and fat layers.

Overlay Measurements by Mueller Polarimetry in Back Focal Plane

Angle resolved Mueller polarimetry implemented as polarimetric imaging of a back focal plane of a high NA microscope objective has already demonstrated a good potential for CD metrology. Here we present the experimental and numerical results indicating that this technique may also be competitive for the measurements of overlay error δ. A series of samples of superimposed gratings with well controlled overlay errors have been manufactured and measured with the angle resolved Mueller polarimeter. The overlay targets were 20-μm wide. When the overlay error is δ is equal to 0, absolute values of elements of real 4×4 Mueller matrix M are invariant by matrix transposition. Otherwise this symmetry breaks down. Consequently, we define the following overlay estimator matrix as E = |M| − |M|t. The simulations show that matrix element E14 is the most sensitive to the overlay error. The scalar estimator of E14 was calculated by averaging the pixel values over a specifically chosen mask. This estimator is found to vary linearly with δ for overlay values up to 50 nm. Our technique allows entering small overlay marks (down to 5-μm wide). Only one target measurement is needed for each overlay direction. The actual overlay value can be determined without detailed simulation of the structure provided two calibrated overlay structures are available for each direction.

Use of Mueller polarimetric imaging for the staging of human colon cancer

In this paper we show the results of multi-spectral Mueller Imaging applied to the analysis of human colon cancer in a backscattering configuration with diffuse light illumination. The analyzed sample behaves as a pure depolarizer. The depolarization power, for both healthy and cancerous zones, is lower for linearly than for circularly polarized incident light for all used wavelengths and increases with increasing wavelength. Based on their visual staging and polarimetric responses, we chose specific zones which we correlated to the histology of the corresponding cuts. The histological examination shows that we see a multilayer interaction in both healthy and abnormal zones, if the light penetration depth is sufficient. The measured depolarization depends on several factors: the presence or absence of tumor, the microscopic structure of cancer (ratio between cellular density and stroma), its exophytic (budding) or endophytic (penetrating) nature, its thickness, the degree of cancer penetration in deeper layers and the nature of healthy tissue left under abnormal layers. These results demonstrate that multi-spectral Mueller imaging can provide useful contrasts for the quick staging of human colon cancer ex-vivo, with additional information about cancerous zones with different microscopic structures.

Overlay measurements by Mueller polarimetry in the back focal plane

Angle resolved Mueller polarimetry implemented as polarimetric imaging of the back focal plane of a high NA microscope objective has already demonstrated a good potential for CD metrology1. In this paper we present the experimental and numerical results which indicate that this technique may also be competitive for measurements of the overlay error δ between two gratings at different levels. Series of samples of superimposed gratings with well controlled overlay errors have been manufactured and measured with the angle resolved Mueller polarimeter. The overlay targets were 20 μm wide. When overlay error δ = 0 the absolute value of Mueller matrix elements is invariant by matrix transposition. This symmetry breaks down when δ ≠ 0. As a result, we can define the following overlay estimator matrix: Ε = |Μ | - |Μ |t. The simulations show that matrix element E14 is the most sensitive to the overlay error. In the experiments the scalar estimator of E14 was defined by averaging the pixel values over specifically chosen mask. The scalar estimator is found to vary essentially linearly with δ for the overlay values up to 50 nm. Our technique allows entering quite small overlay marks (down to 5 μm wide). The only one target measurement is needed for each overlay direction. The actual overlay value can be determined without detailed simulation of the structure provided the two calibrated overlay structures are available for each direction.

Applications of Mueller polarimetry in the Fourier space for overlay characterization in microelectronics

We present a new optical technique using complete Mueller polarimetry in the back focal plane of a microscope objective to characterize the overlay defects in microelectronics industry. Exploiting the fundamental symmetries in the physics of periodic structures and polarized light and the redundancies in the angle-resolved images we prove that it is possible to measure overlay by this fast and non-destructive technique. The simulations of the one-dimensional structures have shown that the values of a chosen criterion exploiting the off-diagonal coefficients symmetries are proportional to the values of overlay defects and can reach 0.25 for a 25nm defect. The accuracy of the polarimeter used for this application becomes even more critical because it is directly linked to the overlay measurement. Beside the redundancies in the acquired data, the angular resolution allows us also to decouple the information along X and Y directions in the Fourier space. Due to this the overlay defect can be characterized and decomposed with respect to these two axes. We show that the proposed new technique is sensitive to both magnitude and sign of the shift. Thus, Mueller polarimetry in the Fourier space (MPFS) offers more parameters for the process quality control compared with conventional spectroscopic ellipsometry (SE). It means that MPFS should be more efficient than SE for the overlay characterization in microelectronic industry.