Medical Imaging : Other diagnostic imaging


Monomeric Fluorescent Protein-Ligand Complexes with Strong Fluorescence in the Far-Red Region

Research from the University of Wisconsin-Washington County in collaboration with the Institute for Stem Cell Biology and Regenerative Medicine in India, has resulted in the development of monomeric variants of the naturally occurring Sandercyanin Fluorescent Protein (SFP) using site-directed mutagenesis. This work has stemmed from earlier research focused on development of the tetrameric form of SFP, a biliverdin-binding lipocalin protein originally isolated from the mucus of the blue walleye fish, Sander vitreus. Monomeric variants of SFP (mSFPs) have been found to possess the same non-covalent, bili-binding characteristics of the tetramer but are one-quarter the size (~18.6kDa) and do not oligomerize. They are therefore anticipated to be more useful in a host of biotechnology applications. Like the tetrameric form, the mSFPs have a large stokes shift (375nm/675nm) and fluoresce in the far-red or near infrared region, which is advantageous for a wide range of applications including investigation of protein-protein interactions, spatial and temporal gene expression, assessing cell biology distribution and mobility, studying protein activity and protein interactions in vivo, as well as cancer research, immunology, and stem cell research and sub-cellular localization. In addition, the newly developed mSFP’s far-red fluorescence is particularly advantageous for in vivo, deep-tissue imaging.

Digital Otoscope for Optimal Access, Visualization

UW–Madison researchers have designed an otoscope featuring a small camera that is mounted on a narrow tip and able to ‘look around’ obstructions such as earwax. The narrow tip also permits other medical instruments to be inserted into the ear while the otoscope is being used (e.g., a curette for removing earwax or foreign objects). A remarkable view of the tympanic membrane is achieved, facilitating proper diagnosis.

Notable features include a disposable, light-conducting speculum sleeve with distal tip smaller than 2 mm. In addition, images may be captured directly from the device and stored in the patient record in compliance with Federal law.

Statistical Imaging Reconstruction Is Faster, Cuts Noise

A UW–Madison researchers has developed an iterative reconstruction method that simultaneously achieves high convergence speed and high parallelizability. The method can work with various medical imaging systems, including CT, magnetic resonance imaging (MRI), X-ray angiography and positron emission tomography (PET).

In general, a nonlinear reconstruction problem is decomposed into separate linear sub-problems that can be solved more efficiently. The statistical image reconstruction process is decomposed into a statistically weighted algebraic reconstruction update sequence. After this step, the image is de-noised using a regularization function.

Monitoring Tissue Fluorescence in Bright Light

UW–Madison researchers have developed a fluorescence imaging process that can be used in surgical suites and other brightly lit environments. Specifically, the imaging process coordinates with rapidly switched ambient room light, which turns off and on at a speed imperceptible to the human eye. Alternatively, research locations such as bioimaging facilities that are traditionally dark can be illuminated – improving productivity and safety. During the periods of darkness, fluorescence signals from microscopes can be detected and imaged without background light interference.

New Peptide-Mimicking Compounds for Anti-Cancer PET Imaging

UW–Madison and USF researchers have developed a new class of RGD mimetic compounds called γ-AApeptides that specifically target tumor integrin αvβ3 and resist being degraded. The γ-AApeptide tracers mimic the structural and functional properties of natural peptide-based tracers but with significantly improved stability.

Evaluating Systemic Cancers

UW–Madison researchers have developed a technique for extending molecular and functional imaging (e.g., PET, fMRI) assessment of the total disease and disease heterogeneity to a variety of different cancers, including systemic types throughout the body.

The method uses a combination of anatomical and functional masking to isolate multiple dispersed lesions from surrounding tissue. In this way, automatic identification tools can target likely tissue on a case-by-case basis, as guided by information about the type of cancer and imaging materials.

First, a patient is administered an imaging agent that identifies tumor tissue. After scanning, a program helps identify and measure the progression of multiple tumor locations based on how and where the agent is taken up. A color-coded output shows measurements at different locations.

Medical Imaging with Better Temporal Fidelity Can Streamline Stroke Care

UW–Madison researchers have developed a method that increases temporal fidelity, sampling density and/or reduces noise of image frames obtained with a system such as CT, MRI or X-ray c-arm. After the images are acquired, a window function is selected and temporally deconvolves the image frames using a minimization technique. A temporal sampling density also may be selected and used in the temporal deconvolution.

Producing Medical Isotopes with Dry-Phase Reactor

UW–Madison researchers have developed an improved method for generating medical isotopes using a dry-phase granular uranium compound, such as uranium salt or oxide.

In the process, the dry granular uranium is exposed to radiation that produces medical isotopes by nuclear reaction. The irradiated uranium then is dissolved in a solvent and the desired isotopes are extracted using standard aqueous separation techniques. The granular uranium material can be dried and reused.

Enhancing Light-Based Tissue Diagnostics by Dimpled Waveguide

UW–Madison researchers have developed a method of controllably and efficiently distributing the intense light available from solid-state light sources (LEDs, laser diodes, "white-light" GaN diodes, superluminescent light diodes) using a planar plate or waveguide film containing a two-dimensional array of conical indentations to distribute and/or concentrate near-point sources of light distributed at the periphery of the array.

The plate, or waveguide, is made of thin glass or other optically transparent material. Impressed into this layer are inverted cone-shaped indentations that are filled or coated by highly reflective silver. When photons from one or more light diodes strike the more numerous cones (the ratio of light sources to dimples can exceed 1:10), the light deflects laterally and radiates in proportion to the density and distribution of the conical indentations. Distributions can range from uniform to highly pixelated spots of high intensity light.

For clinical spectroscopic probes, an array of inverted reflective cones buried in a transparent planar waveguide deflects LED light from the periphery of the guide, focusing it through an array of apertures and onto the tissue to be diagnosed. The light reflected from the tissue bears a signature characteristic of either healthy or cancerous (breast) tissue. This reflected light is detected by an array of annular photodetectors, each surrounding one of the exit apertures.

Generating Medical Isotopes with Safer Vessel and Materials

Wisconsin researchers have developed a ring-shaped, or annular, fissile solution vessel for generating medical isotopes.

The assembly holds three nested chambers. Ions are first directed into an internal target chamber containing a gas. The neutrons that are generated pass outward, through a cooling jacket, into the surrounding fissile solution vessel. This vessel contains an aqueous composition of nuclear material and is shaped to increase heat transfer area to volume. Neutrons strike the nuclear material, generating isotopes and additional neutrons. The solution vessel is separated by another cooling jacket from an outer chamber that reflects neutrons.

Universal Signal-to-Noise Ratio Enhancement Using PICCS Image Reconstruction

UW–Madison researchers have developed a universal method to improve SNR of a digital signal or image, including images produced using any medical imaging modality. The new method implements Dr. Chen’s previous discovery known as “PICCS” (see WARF reference number P08127US), which allows a high quality image to be reconstructed from undersampled image data. A final image with high SNR is constructed by imparting the high SNR characteristics of a “prior image” to the target image. This prior image is created from the original image, which allows an image to be improved without actually obtaining a prior image from the patient.

The first step in the new method is re-sampling, which converts a digital signal or image into a different domain that can be inversed easily for reconstruction purposes. These domains include radon, x-ray, Fourier or wavelet transform. Next, a filter is applied to the re-sampled signal or image to generate a very low noise prior image with low spatial resolution. Then, the PICCS algorithm is applied using the prior image to reconstruct the target signal or image. The resulting final image will have similar noise characteristics as the low-noise prior image, but the degraded spatial resolution will be restored in the iterative image reconstruction procedure.

“DR-PICCS” – Dose Reduction Using PICCS Image Reconstruction Algorithms

UW-Madison researchers have developed a method using existing “PICCS” (prior image constrained compressed sensing) image reconstruction algorithms to reduce radiation dose while attaining quality images with high SNR. Multiple slices of an image volume are collected and then averaged together to create a single thick slice, known as the “prior image,” with high SNR but lacking detailed anatomical structures. The PICCS algorithm then is used to reconstruct each image slice with the original slice thickness using the prior image. The resulting final image has the equivalent image noise variance level of the prior image, the high spatial resolution of the acquired image is preserved and the anatomical features will be detailed.

Noise variance in the final reconstructed image is improved by a factor of approximately the number of slices included in the prior image. Using this method, the patient receives a reduced dose of radiation while the radiologist acquires final images of the same quality currently attained with higher radiation levels.

Integrated, Miniaturized Fiber Optic Probe for Light-Based Diagnostics

UW–Madison and Duke University researchers have developed an integrated fiber optic probe that allows for in vivo sensing of biochemical and morphological changes in local tissue. The probe replaces a spectrometer by bonding thin, flexible photodetector elements directly to the fiber probe tip, which makes local detection of light feasible.  The fiber is processed further to incorporate a mutual ground plane, an insulator and metal lines for transmitting the detected signal. The structure may be constructed to be compact enough to fit within the shaft of a needle, allowing probing of tissue without the need for biopsy. By directly integrating photodetectors with an optical fiber, the probe provides a compact structure that can be placed in close proximity to a sample to increase throughput and decrease cost, making it practical for clinical use.

Real-Time Progressive Medical Image Reconstruction Method for Time-Resolved Data

UW–Madison researchers have developed a method for medical image reconstruction that delivers quality images from time-resolved image data in real time. The method provides accurate images with increased signal-to-noise ratio and temporal resolution while minimizing a patient’s exposure to X-ray radiation.

The method starts with two related images that can be neighboring images from a time series image set or images from the same phase point during repeated motion, such as breathing or the beating of the heart. The images are subtracted to get an image of the difference between the two, which undergoes a sparsifying transformation to reconstruct the final image of interest. All of this is done in real time to achieve more dynamic medical imaging, such as image guided interventional procedures.

Image Reconstruction Method for High Temporal Resolution Image Guided Radiaton Therapy

UW–Madison researchers have developed a medical image reconstruction method designed to increase temporal resolution, while increasing accuracy and reducing the radiation dose to the patient. The method may be applicable to numerous imaging techniques including magnetic resonance imaging (MRI), X-ray computed tomography (CT), positron emission tomography (PET) and single photon emission computed tomography (SPECT).

Acquired data is used to reconstruct a “sparsifying image.” A “correction image” is iteratively determined and subtracted from the sparsifying image to produce a quality image.

The technique also can be applied to current IGRT techniques to increase the accuracy of radiation delivery. Sparsifying images are obtained for a specific phase of the respiratory cycle to more accurately determine the motion characteristics of the target tumor and increase the temporal resolution.

High Temporal Resolution Cardiac CT Imaging with Slowed Gantry Speed

UW-Madison researchers have developed an application of the PICCS image reconstruction method (see WARF reference number P08127US) for producing a time series of images with a higher temporal resolution than the temporal resolution at which the image data was acquired. In cardiac imaging, this allows use of slow gantry rotation for improved image resolution instead of continuing to increase the speed of gantry rotation, which is mechanically challenging.

For high temporal resolution cardiac imaging, a “cone-beam” arrangement such that the focal spot of the X-ray source and the detector define a cone-shaped beam of X-rays is used. The gantry rotation time is counter-intuitively slowed to about 10 seconds. This rotation time enables a single breath-hold for most cardiac patients, which reduces motion during imaging. During the cone-beam CT data acquisition, the ECG-signal will be recorded as 400 to 600 views of the cone-beam projection are simultaneously acquired during each gantry rotation. The acquired data will be used to reconstruct a “prior” image containing the heart that does not contain dynamic information and possibly contains motion-induced streaks. Next, the acquired projection data are “gated” using the ECG data so that there is one projection per heart beat and images can be reconstructed using data from each gated “window”. This allows the PICCS algorithm to accurately reconstruct each cardiac phase. The resulting images have an ultra-high temporal resolution about 20 times better than images obtained using state-of-the-art CT scanners with increased gantry speeds.

Prior Image Constrained Compressed Sensing (PICCS)

UW-Madison researchers have developed a method for reconstructing a high quality image from undersampled image data that is applicable to a number of imaging modalities including CT, MRI and positron emission tomography (PET).

A seed image is acquired by using a prescan, reconstructing a high signal-to-noise (SNR) ratio image from data acquired through any modality, or from a fully sampled data set. This prior seed image is used to iteratively reconstruct a final output image from an undersampled data set taken of the same anatomical structure as the seed image. The high SNR seed image guides a mathematical manipulation of the data set, resulting in a high quality image constrained by the original high SNR image. The method typically requires only two to five iterations to achieve clinically useful images, resulting in a convergence speed much faster than any known iterative image reconstruction methods.

Improved Highly Constrained Image Reconstruction (HYPR) Method

UW-Madison researchers have developed an improvement to the HYPR process in which a higher quality composite image may be produced when subject motion is present during the scan. The composite image is produced by accumulating data from a series of acquired image frames, and the number of image frames used is determined by the amount and nature of subject motion. Subject motion is determined on a pixel-by-pixel basis, and the integration of each pixel with the composite image is based on the detected motion. This adaptation allows the best image possible to be produced when the subject moves during the scan.

The method can be applied to digital subtraction angiography (DSA) and X-ray fluoroscopy by acquiring a series of image frames as a contrast agent flows into the area being imaged. The improved HYPR method then is used to form the composite image on a region-by-region basis.

Nested Waveguides for Generating or Detecting Radiation, Including Terahertz Radiation

UW Madison researchers have recently demonstrated a room temperature, tunable THz source operating at 1.3 THz with an extremely narrow linewidth (< 200 kHz; < 7 x 10-6 cm-1) and record conversion efficiency.  This source takes advantage of a new nested waveguide structure to produce continuously phase-matched difference frequency mixing between spectrally pure, amplified diode laser pumps.  The thin film active medium for this source (LiNbO3 ) is interchangeable with other nonlinear materials operating at other frequency ranges (e.g., AlGaAs for 3.5 THz).  It can be designed to generate ultra-narrow band radiation across a range of frequencies. The device also may be designed to detect THz radiation.

The nested waveguides are fabricated using well established lithography and semiconductor fabrication techniques, such as chemical vapor deposition. A smaller waveguide can be embedded within a larger waveguide.  The smaller waveguide provides guidance for radiation of a shorter wavelength, while the larger waveguide provides a transition to radiation of a longer wavelength. The waveguides enhance the efficiency at which the nonlinear process converts the radiation to the desired frequency by providing strong optical confinement of the input and output radiation, reducing diffraction and improving phase matching. Nested waveguides also have a small footprint, making them ideal for creating small THz-based systems.

Imaging Spectrometer for Early Detection of Skin Cancer

A UW-Madison researcher has developed a portable imaging spectrometer for the early detection of skin cancer. A handheld scanner uses light emitting diodes to illuminate a region of skin and the reflected light is collected by an objective lens. A micro-lens array then divides the region into smaller images that are processed to reveal their spectral content.

Because spectral and image data are acquired in one step, this new device provides two effective indicators to detect skin cancer. Physicians can evaluate the image data while the spectral data is compared to spectra of known cancerous or healthy regions.

Using Endogenous Fluorescence to Identify Cancerous Cells

UW-Madison researchers have developed methods to identify, detect and characterize diseases, such as cancer, using non-linear infrared imaging. Changes in the fluorescent properties of tissue indicate changes in cellular metabolism that may signify the presence of disease. Specifically, the fluorescent properties of flavin adenine dinucleotide (FAD), a redox cofactor involved in several important metabolic reactions, can indicate the presence of cancer, particularly epithelial tumors such as breast tumor cells.

To detect cancer, tissue is exposed to near infrared radiation, which excites endogenous FAD fluorophors. The FAD fluorophors then emit measurable fluorescent signals that vary with different tissue properties. A partially or fully automated system analyzes the signals and compares them to previously acquired reference data. The findings can be used to identify, locate and characterize the presence and stage of carcinomas.

“Super” Artificial Compound Eyes Formed from Microlenses

UW-Madison researchers have now combined many liquid-liquid microlenses on a planar or domed array to form a “super” artificial compound eye (SACE) with a large field of view and high resolution. By coupling the benefits of microlenses with those of compound eyes, this technology could provide low-cost, high-resolution imaging for medical, industrial and military applications. It could be used to develop medical devices, such as fiber endoscopes and laparoscopes, that make procedures like colonoscopy or appendectomy safer and easier. The SACE could perform image scanning without bulky control systems that can be cumbersome and costly. This technology could also improve current monitoring and surveillance instruments for the military, as well as consumer products, such as miniaturized digital cameras.

Using Stromal Collagen to Help Diagnose and Characterize Breast Cancer

UW-Madison researchers have developed an imaging method that may assist in diagnosing cancerous and precancerous conditions in breast tissue. Because breast cancer is frequently associated with the increased deposition of proteins, particularly collagen, in the extracellular matrix, the inventors developed three tumor-associated collagen signatures, or TACS, which provide novel markers for localizing and characterizing breast tumors.

To identify breast carcinomas, nonlinear optical microscopy is used to generate high resolution, 3-D images of a test tissue. The images are then analyzed to detect and characterize any TACS that may exist in the tissue. The degree to which the TACS are present correlates with the onset and progression of cancer, thus providing diagnostic information complementary to conventional diagnostic methods.

Depth-Resolved Reflectance Instrument

UW-Madison researchers have developed an improved reflectance instrument and method to collect and analyze optical information from a pre-cancerous or cancerous target in a turbid medium, such as epithelial tissue. The instrument uses a smart fiber-optic probe to deliver a selected wavelength of light to tissue and sense the reflected light from specific layers. Altering the angles of illumination and detection relative to the tissue surface and the source-detector separation allows the clinician to probe at various depths beneath the surface of the tissue. Specially designed modeling for two-layered tissue enables the user to extract information from each individual layer for diagnosis.

Bright, Tunable, Continuous Wave Coherent Terahertz Source

UW-Madison researchers have developed an intense, narrow-band, tunable source of terahertz radiation. Two THz beams are produced by two pump beams via difference frequency mixing (DFM) in a second order non-linear optical material.

By encasing the optical material between two layers of dielectric cladding material, the researchers were able to dramatically decrease the amount of THz absorbed. The dielectric materials don’t absorb much THz, and provide a waveguide structure that helps confine the beam. This makes it possible for the first time to efficiently couple the exiting THz radiation to a flexible guiding structure, much like a fiber optic cable.

Highly Constrained Image Reconstruction for Medical Imaging Applications

A UW–Madison researcher has developed a new method for reconstructing medical images from projection views of a subject. A backprojection technique is used that does not assume homogeneity in the backprojected signal. A composite image is reconstructed, and then this composite image is used to highly constrain the image reconstruction process to provide more image detail where needed.

This image reconstruction method reduces scan time and radiation dose, and provides higher resolution for time-resolved studies. Acquiring a highly sampled composite image will increases the signal-to-noise ratio (SNR) of the undersampled reconstructed images. This method can be used to improve the reconstruction of medical images.

Continuous-Wave Laser Source for High Speed Spectroscopy

UW-Madison researchers have devised a simple and inexpensive laser-based spectroscopy approach that is similar to FTIR in principle; however, because it has no moving parts, it offers many advantages, including the ability to produce spectra every microsecond or faster. The laser is generally fashioned as a fiber laser, which is a laser cavity composed primarily of fiber optic cable. To measure spectra, the continuous-wave fiber output is directed at the test article and onto a single photoreceiver. The photoreceiver signal is then digitally processed to produce the desired spectra.

Surface Identification Using Microwave Signals for Microwave-Based Detection of Cancer

UW-Madison researchers have now developed a data-adaptive algorithm that uses reflected microwave signals to estimate the location of the skin-breast interface relative to the antenna locations. This approach is based on geometric principles and the fact that the impedance mismatch at the skin-breast interface results in significant backscatter.

First, a matched filter is applied to the backscattered signal in each antenna channel to determine the propagation time from the antenna to the skin-breast interface. The propagation time locates the interface on a circle with a known radius. The breast surface is assumed to be convex and tangent to the circle. A tangent point, which defines the intersection of the circle and breast surface, is determined for each antenna by assuming that the circles centered at adjacent antennas intersect the same tangent line. The resulting set of tangent points from the antenna locations is fit with a curve, which defines the breast-skin interface.

Systems and Methods for the Cyclotron Production of Iodine-124

UW-Madison researchers have developed an improved method for the cyclotron production of I-124 using an aluminum telluride (Al2Te3) target. The method involves producing I-124 from an isotopically enriched aluminum telluride target via the 124Te(p,n) or 124Te(d,2n) reaction. The I-124 formed during irradiation is sublimated from the target stock by dry distillation in a resistive furnace and then swept in a gas stream to a chilled quartz trap downstream. It may be delivered as a solid film on a quartz tube or extracted by scrubbing with a mild base for radio labeling.

Time-Domain Inverse Scattering Techniques for Use in Microwave Imaging

UW-Madison researchers have developed an improved method for estimating the average dielectric properties of breast tissue. The method, an extension of a time-domain inverse scattering technique, greatly reduces the number of unknown parameters in the inverse scattering problem. This allows the average properties of the breast tissue to be more readily estimated for each patient, increasing the accuracy of malignant tissue detection and localization. Simulation studies have shown that this method results in significantly improved detection of malignant tissue.

Microwave-Based Breast Cancer Detection Using Hypothesis Testing

UW-Madison researchers have developed a method of identifying malignant breast tissue that uses hypothesis testing and microwave backscatter measurements. Breast tissue is illuminated with an ultrawideband (UWB) microwave pulse. The resulting backscatter contains contributions from possible tumors, clutter due to the heterogeneous properties of normal breast tissue, and noise.

At multiple locations throughout the breast, a hypothesis test is performed to determine if a tumor is present at that location. Under the tumor absent (null) hypothesis, the measured backscatter data is assumed to consist of clutter plus noise. Under the alternative hypothesis, the measured data is assumed to consist of backscatter from a tumor at that location plus clutter and noise. A test statistic is computed for each location in the breast and compared to a threshold to determine which hypothesis is most likely given the measured data. The resulting information indicates the location of detected tumors in the breast.

This approach offers improved patient comfort and safety compared to X-ray mammography and reduced cost compared to MRI. Furthermore, it may offer improved accuracy over conventional X-ray mammography.

Depth-Resolved Fluorescence Instrument for Detecting Epithelial Pre-Cancers and Cancers

UW-Madison researchers have developed a fluorescence instrument and technique that enables measurement of fluorescent targets, such as pre-cancerous or cancerous growths, at various depths below the tissue surface. The technique involves using the fluorescence instrument to illuminate the tissue surface with light of a selected wavelength and collect the fluorescent light emanating from the tissue. To probe at various depths beneath the tissue surface, the size of the the device's illumination and collection aperture is varied  By allowing characterization of the depth-dependent distribution of the fluorescent target, this technique maximizes the contrast between cancerous or pre-cancerous growth and normal tissue. It also yields additional information about the stage of cancers or pre-cancers in human epithelial tissue, and may provide important evidence for clinical diagnosis.

Space-Time Microwave Imaging for Breast Cancer Detection

UW-Madison researchers have now developed a novel imaging technique for detecting early-stage breast cancer called microwave imaging via space-time, or MIST for short. MIST makes use of the sharp contrast in dielectric properties between breast carcinomas and normal breast tissue at microwave frequencies.

In the technique, a woman lies on her back and a scanner containing a number of antennas is placed near the center of the breast. Each antenna transmits a very short burst of low-power microwave energy and records the microwave backscatter, which occurs significantly only from malignant tissue. Because the intrinsic contrast between malignant and normal breast tissue is much greater at microwave than at X-ray frequencies, MIST could allow detection of extremely small (i.e., millimeter size) breast tumors, and reduce the number of false-negatives associated with conventional X-ray mammography.

Standardized Compositions That Facilitate Swallowing in Dysphagic Patients

A Wisconsin researcher has developed a viscosity-standardized set of solutions that can be used for diagnosing dysphagia. The set includes “thin,” “nectar thick,” and “honey thick” compositions, all with known viscosities and appealing tastes. To diagnose dysphagia, patients swallow each of the solutions in turn, and their ability to swallow is evaluated either by physical examination, radiography or other means. Ultimately, the recommended dietary fluid intake is matched to the diagnostic material the patient swallowed most easily.