Amplitude- and frequency-dependent activation of layer II/III neurons by intracortical microstimulation.

Intracortical microstimulation (ICMS) has been used for the development of brain machine interfaces. However, further understanding about the spatiotemporal responses of neurons to different electrical stimulation parameters is necessary to inform the design of optimal therapies. In this study, we employed electrophysiological recording, two-photon calcium imaging, and electric field simulation to evaluate the acute effect of ICMS on layer II/III neurons.

Effect of direct voltage induction by low-frequency security systems on neurostimulator lead.

Low-frequency (LF) security systems, such as antitheft electronic article surveillance (EAS) gates emit strong magnetic fields that could potentially interfere with neurostimulator operation. Some patients reported pain and shocking sensations near EAS gates, even after they turned off their pulse generator. To investigate the direct voltage induction of EAS systems on neurostimulator leads, we evaluated voltages induced by two EAS systems (14 kHz continuous wave or 58 kHz pulsed) on a 40 cm sacral neurostimulator lead formed in a circular loop attached to a pulse generator that was turned off.

Using in vivo fluorescence lifetime imaging to detect HER2-positive tumors.

Background: Assessment of the status of tumor biomarkers in individual patients would facilitate personalizing treatment strategy, and continuous monitoring of those biomarkers and their binding process to the therapeutic drugs would provide a means for early evaluation of the efficacy of therapeutic intervention. Fluorescent probes can accumulate inside the tumor region due to the leakiness of its vascularization and this can make it difficult to distinguish if the measured fluorescence intensity is from probes bound to target receptors or just accumulated unbound probes inside the tumor. In this paper, we have studied the fluorescence lifetime as a means to distinguish bound HER2 specific affibody probes to HER2 receptors.

Facial Plethora: Modern Technology for Quantifying an Ancient Clinical Sign and Its Use in Cushing Syndrome.

Context: Facial plethora is a clinical sign described since ancient times for a variety of diseases. In the 19th century, it was linked to increased blood volume or flow, but this has never been proven. Facial plethora is also one of the earliest described clinical features of Cushing's syndrome (CS).

Relative brain signature: a population-based feature extraction procedure to identify functional biomarkers in the brain of alcoholics.

Background: A novel feature extraction technique, Relative-Brain-Signature (RBS), which characterizes subjects' relationship to populations with distinctive neuronal activity, is presented. The proposed method transforms a set of Electroencephalography's (EEG) time series in high dimensional space to a space of fewer dimensions by projecting time series onto orthogonal subspaces.

Methods: We apply our technique to an EEG data set of 77 abstinent alcoholics and 43 control subjects.

Prefrontal cortex hemodynamics and age: a pilot study using functional near infrared spectroscopy in children.

Cerebral hemodynamics reflect cognitive processes and underlying physiological processes, both of which are captured by functional near infrared spectroscopy (fNIRS). Here, we introduce a novel parameter of Oxygenation Variability directly obtained from fNIRS data -the OV Index-and we demonstrate its use in children. fNIRS data were collected from 17 children (ages 4-8 years), while they performed a standard Go/No-Go task.

Multiscale BerEp4 molecular imaging of microtumor phantoms: toward theranostics for basal cell carcinoma.

Basal cell carcinoma (BCC), the most common cancer in humans, appears macroscopically and microscopically similar to many other skin lesions, which makes differential diagnosis difficult. We are developing an approach for quantitative molecular imaging of BerEP4, a transmembrane biomarker for BCC, with the goal of increasing the precision and accuracy of diagnosis. This pilot study was conducted to assess the affinity and selectivity of BerEp4 antibody and assess its possible use in designing theranostic probes for BCC.

In vivo fluorescence lifetime imaging for monitoring the efficacy of the cancer treatment.

Purpose: Advances in tumor biology created a foundation for targeted therapy aimed at inactivation of specific molecular mechanisms responsible for cell malignancy. In this paper, we used in vivo fluorescence lifetime imaging with HER2-targeted fluorescent probes as an alternative imaging method to investigate the efficacy of targeted therapy with 17-DMAG (an HSP90 inhibitor) on tumors with high expression of HER2 receptors.

Experimental Design: HER2-specific Affibody, conjugated to Alexafluor 750, was injected into nude mice bearing HER2-positive tumor xenograft.

Evaluation of non-invasive multispectral imaging as a tool for measuring the effect of systemic therapy in Kaposi sarcoma.

Diffuse multi-spectral imaging has been evaluated as a potential non-invasive marker of tumor response. Multi-spectral images of Kaposi sarcoma skin lesions were taken over the course of treatment, and blood volume and oxygenation concentration maps were obtained through principal component analysis (PCA) of the data. These images were compared with clinical and pathological responses determined by conventional means.

In vivo assessment of HER2 receptor density in HER2-positive tumors by near-infrared imaging, using repeated injections of the fluorescent probe.

HER2 overexpression and amplification of the HER2/neu gene have been found in approximately 25% of invasive breast carcinomas. They are associated with a poor prognosis and resistance to therapy in breast cancer patients. Up to now, clinical evaluation of human epidermal growth factor receptor 2 (HER2) expression is based on ex vivo methods (immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH) staining of biopsied tissue).

Biophotonics techniques for structural and functional imaging, in vivo.

In vivo optical imaging is being conducted in a variety of medical applications, including optical breast cancer imaging, functional brain imaging, endoscopy, exercise medicine, and monitoring the photodynamic therapy and progress of neoadjuvant chemotherapy. In the past three decades, in vivo diffuse optical breast cancer imaging has shown promising results in cancer detection, and monitoring the progress of neoadjuvant chemotherapy. The use of near infrared spectroscopy for functional brain imaging has been growing rapidly.

Affibody-DyLight conjugates for in vivo assessment of HER2 expression by near-infrared optical imaging.

Purpose: Amplification of the HER2/neu gene and/or overexpression of the corresponding protein have been identified in approximately 20% of invasive breast carcinomas. Assessment of HER2 expression in vivo would advance development of new HER2-targeted therapeutic agents and, potentially, facilitate choice of the proper treatment strategy offered to the individual patient. We present novel HER2-specific probes for in vivo evaluation of the receptor status by near-infrared (NIR) optical imaging.

In vivo method to monitor changes in HER2 expression using near-infrared fluorescence imaging.

Human epidermal growth factor receptor type 2 (HER2) is a well-known biomarker that is overexpressed in many breast carcinomas. HER2 expression level is an important factor to optimize the therapeutic strategy and monitor the treatment. We used albumin binding domain-fused HER2-specific Affibody molecules, labeled with Alexa Fluor750 dye, to characterize HER2 expression in vivo.

Biophotonics techniques for structural and functional imaging, in vivo.

In vivo optical imaging is being conducted in a variety of medical applications, including optical breast cancer imaging, functional brain imaging, endoscopy, exercise medicine, and monitoring the photodynamic therapy and progress of neoadjuvant chemotherapy. In the past three decades, in vivo diffuse optical breast cancer imaging has shown promising results in cancer detection, and monitoring the progress of neoadjuvant chemotherapy. The use of near infrared spectroscopy for functional brain imaging has been growing rapidly.

In vivo fluorescence lifetime imaging monitors binding of specific probes to cancer biomarkers.

One of the most important factors in choosing a treatment strategy for cancer is characterization of biomarkers in cancer cells. Particularly, recent advances in Monoclonal Antibodies (MAB) as primary-specific drugs targeting tumor receptors show that their efficacy depends strongly on characterization of tumor biomarkers. Assessment of their status in individual patients would facilitate selection of an optimal treatment strategy, and the continuous monitoring of those biomarkers and their binding process to the therapy would provide a means for early evaluation of the efficacy of therapeutic intervention.

A hematoma detector-a practical application of instrumental motion as signal in near infra-red imaging.

In this paper we discuss results based on using instrumental motion as a signal rather than treating it as noise in Near Infra-Red (NIR) imaging. As a practical application to demonstrate this approach we show the design of a novel NIR hematoma detection device. The proposed device is based on a simplified single source configuration with a dual separation detector array and uses motion as a signal for detecting changes in blood volume in the dural regions of the head.

Artifact reduction method in ultrasound-guided diffuse optical tomography using exogenous contrast agents.

In diffuse optical tomography (DOT), a typical perturbation approach requires two sets of measurements obtained at the lesion breast (lesion or target site) and a contra-lateral location of the normal breast (reference site) for image reconstruction. For patients who have a small amount of breast tissue, the chest-wall underneath the breast tissue at both sites affects the imaging results. In this group of patients, the perturbation, which is the difference between measurements obtained at the lesion and reference sites, may include the information of background mismatch which can generate artifacts or affect the reconstructed quantitative absorption coefficient of the lesion.

Potential role of coregistered photoacoustic and ultrasound imaging in ovarian cancer detection and characterization.

Currently, there is no adequate technology to detect early stage ovarian cancers. Most of the cancers in the ovary are detected when the cancer has already metastasized to other parts of the body. As a result, ovarian cancer has the highest mortality of all gynecologic cancers with a 5-year survival rate of 30% or less.

Optical tomography method that accounts for tilted chest wall in breast imaging.

The chest wall underneath breast tissue distorts light reflection measurements, especially measurements obtained from distant source-detector pairs. For patients with a chest wall located at a shallower depth, the chest-wall effect needs to be considered in the image reconstruction procedure. Following our previous studies, this work systemically evaluates the performance of a two-layer model-based reconstruction using the finite element method, and compares it with the performance of the semi-infinite model.

Early-stage invasive breast cancers: potential role of optical tomography with US localization in assisting diagnosis.

Purpose: To investigate the potential role of optical tomography in the near-infrared (NIR) spectrum with ultrasonographic (US) localization as a means of differentiating early-stage cancers from benign lesions of the breast.

Materials And Methods: The protocol was approved by the institutional review boards and was HIPAA compliant; all participants signed an informed consent. One hundred seventy-eight consecutive women (mean age, 52 years; range, 21-89 years) who underwent US-guided biopsy were imaged with a hand-held probe consisting of a coregistered US transducer and an NIR imager.

Effect of the chest wall on breast lesion reconstruction.

The chest wall underneath the breast tissue affects near-infrared (NIR) diffusive waves measured with reflection geometry. With the assistance of a co-registered ultrasound, the depth and the tilting angle of the chest wall can be determined and are used to model the breast as a two-layer medium. Finite element method (FEM) is suitable for modeling complex boundary conditions and is adapted to model the breast tissue and chest wall.

Image reconstruction method for a two-layer tissue structure accounts for chest-wall effects in breast imaging.

We develop a new tomographic imaging reconstruction algorithm for a two-layer tissue structure. Simulations and phantom experiments show more accurate reconstruction of target optical properties compared with those results obtained from a semi-infinite tissue model for layered structures. This improvement is mainly attributed to the more accurate estimation of background optical properties and more accurate estimation of weight matrix for imaging reconstruction by considering the light propagation effect in the second layer.