Iven Jose

Non-invasive imaging of breast cancer: synthesis and study of novel near-infrared fluorescent estrogen conjugate

The use of near-infrared (NIR) spectroscopy to interrogate deeper tissue volume has shown enormous potential for molecular-based non-invasive imaging when coupled with appropriate excitable dyes. As most of the breast cancers are hormone dependent hence determination of the hormonal receptor status gains paramount importance when deciding the treatment regime for the patient. Since proliferations of the breast cancer cells are often driven by estrogen, we focus on to developing a technique to detect estrogen receptor status. As a first step, the objective of this work was to synthesize and characterize one such novel NIR fluorescent (NIRF) conjugate, which could potentially be used to detect estrogen receptors. The conjugate was synthesized by ester formation between 17-b estradiol and a cyanine dye namely: bis-1, 1-(4-sulfobutyl) indotricarbocyanine-5-carboxylic acid, sodium salt. The cyanine dye is a hydrophilic derivative of indocyanine green (ICG). The ester formed was found to have an extra binding ability with the receptor cites as compared to ICG, which was established by the partition coefficient studies. This cyanine dye has a partition coefficient less than 0.005 as compared to that of ICG (>200)[1]. In addition the ester showed enhanced fluorescent quantum yield than ICG. The replacement of the sodium ion in the ester by a larger glucosammonium ion was found to enhance the hydrophilicity and reduce the toxic effect on the cell lines. The excitation and emission peaks for the conjugate were recorded in the NIR region as 750nm and 788nm respectively. The ester developed was tested on the breast cancer cell lines MCF-7 and found non-toxic. The tagging characteristics were pivotal determinants underlying the ability of the fluorescent conjugate in binding the estrogen receptor of the breast cancer cells. This technique offers the potential of non-invasive detection of hormone receptor status in vivo and may help in decreasing the load of unnecessary biopsies. Here, we have reported the progress made in the development of a novel NIR external contrast agent and the work is in progress to use this conjugate for the molecular-based, diagnostic imaging of breast cancer.

Monitoring Nyiragongo Volcano Using a Federated Cloud-Based Wireless Sensor Network

Current Nyiragongo Volcano observatory systems yield poor monitoring quality due to unpredictable dynamics of volcanic activities and limited sensing capability of existing sensors (seismometers, acoustic microphones, GPS, tilt-meter, optical thermal, and gas flux).The sensor node has limited processing capacity and memory. So if some tasks from the sensor nodes can be uploaded to the server of cloud computing then the battery life of the sensor nodes can be extended. The cloud computing can be used both for processing of aggregate query and storage of data. The two principal merits of this paper are the clear demonstration that the Cloud Computing model is a good fit with the dynamic computational requirements of Nyiragongo volcano monitoring and the novel optimization algorithm for seismic data routing.The proposed new model has been evaluated using ArduinoAtmega328 as hardware platform, Eucalyptus/Open Stack with Orchestra-Juju for Private Sensor Cloud connected to some famous public clouds such as Amazon EC2, ThingSpeak, SensorCloud and Pachube.

P-phase picker using virtual cloud-based Wireless Sensor Networks

Wireless Sensor Networks, mainly regarded as numerous resource-limited nodes linked via low bandwidth, have been intensively deployed for active volcano monitoring during the few past years. This paper studies the problem of primary waves received by seismic wireless sensors suffering from limited bandwidth, processing capacity, battery life and memory. To address these challenges, a new P-phase picking approach where sensors are virtualized using cloud computing architecture followed by a novel in-network signal processing algorithm, is proposed. The two principal merits of this paper are the clear demonstration that the Cloud Computing model is a good fit with the dynamic computational requirements of volcano monitoring and the novel signal processing algorithm for accurate P-phases picking. The proposed new model has been evaluated on Mount Nyiragongo using Eucalyptus/Open Stack with Orchestra-Juju for Private Sensor Cloud then to some famous public clouds such as Amozon EC2, ThingSpeak, SensorCloud and Pachube. The testing has been successful at 75%. The recommendation for future work would be to improve the effectiveness of virtual sensors by applying optimization techniques and other methods.

Computationally Efficient Wavelet Domain Solver for Florescence Diffuse Optical Tomography

Estrogen induced proliferation of mutant cells is a growth signal hallmark of breast cancer. Fluorescent molecule that can tag Estrogen Receptor (ER) can be effectively used for detecting cancerous tissue at an early stage. A novel target-specific NIRf dye conjugate aimed at measuring ER status was synthesized by ester formation between 17-β estradiol and a hydrophilic derivative of ICG, cyanine dye, bis-1,1-(4-sulfobutyl) indotricarbocyanine-5-carboxylic acid, sodium salt. In-vitro studies provided specific binding on ER+ve [MCF-7] cells clearly indicating nuclear localization of the dye for ER+ve as compared to plasma level staining for MDA-MB-231. Furthermore, cancer prone cells showed 4.5-fold increase in fluorescence signal intensity compared to control. A model of breast phantom was simulated to study the in-vivo efficiency of dye with the parameters of dye obtained from photo-physical and in-vitro studies. The excitation (754 nm) and emission (787 nm) equation are solved independently using parallel processing strategies. The results were obtained by carrying out wavelet transformation on forward and the inverse data sets. An improvisation of the Information content of system matrix was suggested in wavelet domain. The inverse problem was addressed using Levenberg–Marquardt (LM) procedure with the minimization of objective function using Tikhonov approach. The multi resolution property of wavelet transform was explored in reducing error and increasing computational efficiency. Our results were compared with the single resolution approach on various parameters like computational time, error function, and Normalized Root Mean Square (NRMS) error. A model with background absorption coefficient of 0.01 mm-1 with anomalies of 0.02 mm-1 with constant reduced scattering of 2.0 mm for different concentration of dye was compared in the result. The reconstructed optical properties were in concurrence with the tissue property at 787 nm. We intend our future plans on in-vivo study on developing a complete instrumentation for imaging a target specific lipophilic dye.

Early detection of Breast Cancer: A Molecular Optical Imaging approach using novel estrogen conjugate fluorescent dye

Estrogen induced proliferation of mutant cells is widely understood to be the one of major risk determining factor in the development of breast cancer. Hence determination of the Estrogen Receptor[ER] status is of paramount importance if cancer pathogenesis is to be detected and rectified at an early stage. Near Infrared Fluorescence [NIRf] Molecular Optical Imaging is emerging as a powerful tool to monitor bio-molecular changes in living subjects. We discuss pre-clinical results in our efforts to develop an optical imaging diagnostic modality for the early detection of breast cancer. We have successfully carried out the synthesis and characterization of a novel target-specific NIRf dye conjugate aimed at measuring Estrogen Receptor[ER] status. The conjugate was synthesized by ester formation between 17-β estradiol and a hydrophilic derivative of Indocyanine Green (ICG) cyanine dye, bis-1,1-(4-sulfobutyl) indotricarbocyanine-5-carboxylic acid, sodium salt. In-vitro studies regarding specific binding and endocytocis of the dye performed on ER+ve [MCF-7] and control [MDA-MB-231] adenocarcinoma breast cancer cell lines clearly indicated nuclear localization of the dye for MCF-7 as compared to plasma level staining for MDA-MB-231. Furthermore, MCF-7 cells showed ~4.5-fold increase in fluorescence signal intensity compared to MDA-MB-231. A 3-D mesh model mimicking the human breast placed in a parallel-plate DOT Scanner is created to examine the in-vivo efficacy of the dye before proceeding with clinical trials. Photon migration and florescence flux intensity is modeled using the finite-element method with the coefficients (quantum yield, molar extinction co-efficient etc.) pertaining to the dye as obtained from photo-physical and in-vitro studies. We conclude by stating that this lipophilic dye can be potentially used as a target specific exogenous contrast agent in molecular optical imaging for early detection of breast cancer.

Novel Design for RF MEMS Capacitive Shunt Switch in K and Ku Bands

A novel design for RF MEMS Capacitive Shunt Switch with operating bandwidth in the K and Ku bands is presented in this paper. The novel MEMS switch has got lower insertion loss than a normal switch and there is no compromise on the isolation and the operating bandwidth of the switch. The resonant frequency of the proposed switch is kept constant near 20GHz which is the midpoint of the bandwidth of the switch. A comparative study of a normal switch and the proposed switch is done. The improvement in design has been achieved by introducing discontinuities in the coplanar waveguide both in the central conductor and the ground planes. The discontinuities are represented in terms of equivalent lumped parameters. A new method of obtaining the lumped parameters of coplanar waveguide step discontinuities in the central conductor and ground planes using full wave electromagnetic simulation is also presented.

Estrogen receptor-targeted optical imaging of breast cancer cells with near-infrared fluorescent dye

Molecular imaging provides the in vivo characterization of cellular molecular events involved in normal and pathologic processes. With the advent of optical molecular imaging, specific molecules, proteins and genes may be tagged with a luminescent reporter and visualized in small animals. This powerful new tool has pushed in vivo optical imaging to the forefront as it allows for direct determination of drug bio-distribution and uptake kinetics as well as an indicator of biochemical activity and drug efficacy. Although optical imaging encompasses diverse techniques and makes use of various wavelengths of light, a great deal of excitement in molecular research lies in the use of tomographic and fluorescence techniques to image living tissues with near-infrared (NIR) light. Nonionizing, noninvasive near-infrared optical imaging has great potential to become promising alternative for breast cancer detection. Fluorescence spectroscopy studies of human tissue suggest that a variety of lesions show distinct fluorescence spectra compared to those of normal tissue. It has also been shown that exogenous dyes exhibit selective uptake in neoplastic lesions and may offer the best contrast for optical imaging. Use of exogenous agents would provide fluorescent markers, which could serve to detect embedded tumors in the breast. In particular, the ability to monitor the fluorescent yield and lifetime may also enable biochemical specificity if the fluorophore is sensitive to a specific metabolite, such as oxygen. As a first step, we have synthesized and characterized one such NIR fluorescent dye conjugate, which could potentially be used to detect estrogen receptors (ER)[2] . The conjugate was synthesized by ester formation between 17-β estradiol and a hydrophilic derivative of indocyanine green (ICG) cyanine dye, bis-1, 1-(4-sulfobutyl) indotricarbocyanine-5- carboxylic acid, sodium salt. The ester formed was found to have an extra binding ability with the receptor cites as compared to ICG, which was established by the partition coefficient studies. The replacement of the sodium ion in the ester by a larger glucosammonium ion was found to enhance the hydrophilicity and reduce the toxic effect on the cell lines. The excitation and emission peaks for the conjugate were recorded in the NIR region as 750nm and 788nm respectively. The ester was found nontoxic on adenocarcinoma breast cancer cell lines MCF-7/MDA-MB-231. Specific binding and endocytosis of the estrogen-labeled conjugate was studied on the MCF-7 (ER positive) and MDA-MB-231 (ER negative). Conjugate staining of MCF-7 cells showed ~ 4-fold increase in signal intensity compared to MDA-MB- 231. Further, estrogen molecules were found to be specifically localized to the nuclear region of MCF-7 cells, whereas MDA-MB-231 showed plasma membrane staining. This technique offers the potential of noninvasive detection of hormone receptor status in breast cancer cells and would help in decreasing the load of unnecessary biopsies. Here, we have reported the progress made in the development of a novel NIR external contrast agent and the work is in progress to use this conjugate for the molecular based, diagnostic imaging of breast cancer.