Matthew R. Kiser

Exploring the transport of plant metabolites using positron emitting radiotracers.

Short‐lived positron‐emitting radiotracer techniques provide time‐dependent data that are critical for developing models of metabolite transport and resource distribution in plants and their microenvironments. Until recently these techniques were applied to measure radiotracer accumulation in coarse regions along transport pathways. The recent application of positron emission tomography (PET) techniques to plant research allows for detailed quantification of real‐time metabolite dynamics on previously unexplored spatial scales. PET provides dynamic information with millimeter‐scale resolution on labeled carbon, nitrogen, and water transport over a small plant‐size field of view. Because details at the millimeter scale may not be required for all regions of interest, hybrid detection systems that combine high‐resolution imaging with other radiotracer counting technologies offer the versatility needed to pursue wide‐ranging plant physiological and ecological research. In this perspective we describe a recently developed hybrid detection system at Duke University that provides researchers with the flexibility required to carry out measurements of the dynamic responses of whole plants to environmental change using short‐lived radiotracers. Following a brief historical development of radiotracer applications to plant research, the role of radiotracers is presented in the context of various applications at the leaf to the whole‐plant level that integrates cellular and subcellular signals and/or controls.

Neutron Stimulated Emission Computed Tomography for Diagnosis of Breast Cancer

Neutron stimulated emission computed tomography (NSECT) is being developed as a non-invasive spectroscopic imaging technique to determine element concentrations in the human body. NSECT uses a beam of fast neutrons that scatter inelastically from atomic nuclei in tissue, causing them to emit characteristic gamma photons that are detected and identified using an energy-sensitive gamma detector. By measuring the energy and number of emitted gamma photons, the system can determine the elemental composition of the target tissue. Such determination is useful in detecting several disorders in the human body that are characterized by changes in element concentration, such as breast cancer. In this paper we describe our experimental implementation of a prototype NSECT system for the diagnosis of breast cancer and present experimental results from sensitivity studies using this prototype. Results are shown from three sets of samples: (a) excised breast tissue samples with unknown element concentrations, (b) a multi-element calibration sample used for sensitivity studies, and (c) a small-animal specimen, to demonstrate detection ability from in-vivo tissue. Preliminary results show that NSECT has the potential to detect elements in breast tissue. Several elements were identified common to both benign and malignant samples, which were confirmed through neutron activation analysis (NAA). Statistically significant differences were seen for peaks at energies corresponding to 37Cl, 56Fe, 58Ni, 59Co, 79Br and 87Rb. The spectrum from the small animal specimen showed the presence of 12C from tissue, from bone, and elements 39K, 27Al, 37Cl, 56Fe, 68Zn and 25Mg. Threshold sensitivity for the four elements analyzed was found to range from 0.3 grams to 1 gram, which is higher than the microgram sensitivity required for cancer detection. Patient dose levels from NSECT were found to be comparable to those of screening mammography.

Experimental detection of iron overload in liver through neutron stimulated emission spectroscopy

Iron overload disorders have been the focus of several quantification studies involving non-invasive imaging modalities. Neutron spectroscopic techniques have demonstrated great potential in detecting iron concentrations within biological tissue. We are developing a neutron spectroscopic technique called neutron stimulated emission computed tomography (NSECT), which has the potential to diagnose iron overload in the liver at clinically acceptable patient dose levels through a non-invasive scan. The technique uses inelastic scatter interactions between atomic nuclei in the sample and incoming fast neutrons to non-invasively determine the concentration of elements in the sample. This paper discusses a non-tomographic application of NSECT investigating the feasibility of detecting elevated iron concentrations in the liver. A model of iron overload in the human body was created using bovine liver tissue housed inside a human torso phantom and was scanned with a 5 MeV pulsed beam using single-position spectroscopy. Spectra were reconstructed and analyzed with algorithms designed specifically for NSECT. Results from spectroscopic quantification indicate that NSECT can currently detect liver iron concentrations of 6 mg g(-1) or higher and has the potential to detect lower concentrations by optimizing the acquisition geometry to scan a larger volume of tissue. The experiment described in this paper has two important outcomes: (i) it demonstrates that NSECT has the potential to detect clinically relevant concentrations of iron in the human body through a non-invasive scan and (ii) it provides a comparative standard to guide the design of iron overload phantoms for future NSECT liver iron quantification studies.

Design and Development of a High-Energy Gamma Camera for Use With NSECT Imaging: Feasibility for Breast Imaging

A new spectroscopic imaging technique, neutron stimulated emission computed tomography (NSECT), is currently being developed to non-invasively and non-destructively measure and image elemental concentrations within the body. NSECT has potential for use in breast imaging as several studies have shown a link between elemental concentration and tumor status. In NSECT, a region of interest is illuminated with a high-energy (3-5 MeV) beam of neutrons that scatter inelastically with elemental nuclei within the body. The characteristic gamma rays that are emitted as the excited nuclei relax allow the identification of elements and the formation of elemental composition images. This imaging technique requires high-resolution and high-energy gamma spectroscopy; thereby eliminating current scintillation crystal based position sensitive gamma cameras. Instead, we propose to adapt high-energy gamma imaging techniques used in space-based imaging. A high purity germanium (HPGe) detector provides high-resolution energy spectra while a rotating modulation collimator (RMC) placed in front of the detector modulates the incoming signal to provide spatial information. Counting the number of gamma events at each collimator rotation angle allows for reconstruction of images. Herein we report on the design and testing of a prototype RMC, a Monte Carlo simulation of this camera, and the use of this simulation tool to access the feasibility of imaging a breast with such a camera. The prototype RMC was tested with a 22Na point source and verified that the RMC modulates the gamma rays in a predictable manner. The Monte Carlo simulation accurately modeled this behavior. Other simulations were used to accurately reconstruct images of a point source located within a 10 cm cube, suggesting NSECTs potential as a breast imaging method.

Non-invasive quantification of iron /sup 56/Fe in beef liver using neutron stimulated emission computed tomography

Neutron spectroscopy is being developed as a non-invasive tool to measure element concentration in the body at molecular levels. We are developing a neutron stimulated emission computed tomography (NSECT) system to identify element concentrations in tissue, using inelastic scattering of neutrons by target nuclei. An incident neutron scatters inelastically with an atomic nucleus to emit a gamma photon whose energy is characteristic of the scattering nucleus. This energy is detected by an energy-sensitive gamma detector to identify the target atom. Here we describe an experiment to non-invasively determine the concentration of natural iron (/sup 56/Fe) in beef liver. A 7.5 MeV neutron beam was used to scan a known quantity of solid iron and establish a ratio of iron concentration to gamma counts for the experimental setup. A known quantity of beef liver was then scanned using the same experimental setup, to obtain gamma spectra showing element concentrations in the liver. Counts from gamma peaks corresponding to excited states in iron were compared with counts from the known iron sample, to yield the iron concentration in the liver. A high purity germanium (HPGe) detector was used to measure the emitted gamma energy. Although the results obtained in this experiment are slightly higher than normal iron limits reported in various studies, they demonstrate the techniques ability to non-invasively quantify iron concentration in a biological organ.

Non-Invasive Estimation of Potassium (39K) in Bovine Liver Using Neutron Stimulated Emission Computed Tomography (NSECT)

Neutron stimulated emission computed tomography (NSECT) is being developed as a non-invasive technique to measure element concentration in in-vivo tissue at molecular levels. We have developed a system that performs this task using an incident neutron beam that scatters inelastically with an atomic nucleus causing it to emit a characteristic gamma photon. An energy-sensitive gamma detector is used to detect this energy and identify the target atom. Here we describe an experiment to determine the concentration of natural potassium (39K) in bovine liver without the need for a biopsy. A 5 MeV neutron beam was used to scan a known quantity of bovine liver to obtain a gamma spectrum showing element concentration in the liver. An aqueous KCl solution calibration sample was then scanned to establish a ratio of potassium concentration to gamma counts for the experimental setup. Counts from gamma peaks corresponding to excited states in 39K were summed and compared with counts from the known calibration sample, to give the concentration of 39K in the liver. A high purity germanium (HPGe) clover detector was used to measure the emitted gamma energy. The results were validated through neutron activation analysis (NAA) of the liver sample. The concentration of 39K reported by NSECT was found to be within 13% of the NAA result, clearly demonstrating the ability of NSECT for non-invasive quantification of element concentration in tissue.

Neutron Spectroscopy of Mouse Using Neutron Stimulated Emission Computed Tomography (NSECT)

Neutron spectroscopy is evolving as a non-invasive technique to measure element concentration in biological tissue. We have developed a neutron stimulated emission computed tomography (NSECT) system that maps the elemental composition of a body through a non-invasive scan. A neutron beam incident on a sample energizes the samples atomic nuclei through inelastic scatter interactions. These energized nuclei then spontaneously return to their ground energy states emitting the extra energy as a characteristic gamma photon. An energy-sensitive gamma detector is used to detect this energy and hence identify the emitting atom. Such a technique has several applications in both humans and small animals. Here we demonstrate NSECTs feasibility in scanning small animals, and show results from a spectroscopic examination of a fixed mouse specimen. The mouse was flushed with saline and fixed using a gadolinium/formalin solution. Scanning was performed using a 5 MeV monochromatic neutron beam. Background was corrected using time-of-flight correction to reduce time-uncorrelated noise and polynomial curve-fit subtraction to remove the residual underlying background. The emitted gammas were measured using a high purity germanium (HPGe) clover detector. The resulting spectrum shows various peaks corresponding to elements expected in this specimen such as C, Ca and Gd, several other potential matches such as K and Zn, as well as some system related elements such as Fe, Al and Ge from the detector. This experiment demonstrates the ability of NSECT to obtain element information from an intact small animal specimen through a single non-invasive scan.

Neutron Stimulated Emission Computed Tomography (NSECT) for Early Detection of Breast Cancer

Neutron stimulated emission computed tomography (NSECT) is being developed as a non-invasive spectroscopic technique to determine element concentrations in the human body. We have implemented an NSECT system that uses a beam of high-energy neutrons to identify element concentrations in tissue and create 2-dimensional maps of elemental distribution through a single non-invasive tomographic scan. Neutrons scatter inelastically with atomic nuclei in tissue, causing them to emit characteristic gamma photons. These gamma photons are detected and identified using an energy-sensitive gamma detector. By measuring the energy and number of emitted gamma photons, the system can determine the elemental composition of the target tissue. NSECT has the advantage of being able to detect breast cancer at very early stages compared to anatomic screening techniques, as it detects changes in trace element concentrations in the breast, which usually occur before anatomical features such as tumors and micro-calcifications appear. The tomographic scanning system eliminates the need for breast compression and patient disrobing. The system design can be made portable by using a commercially available portable neutron source with a gamma detector. From our preliminary results, NSECT shows significant promise in early diagnosis of breast cancer. It has the potential to evolve into an easily accessible screening modality and diagnostic technique for breast cancer, which can detect and identify malignant tissue in the breast and generate a two-dimensional image through a single non-invasive tomographic scan. Patient dose levels from NSECT are comparable to those of screening mammography. Efforts are under way to achieve the micro-gram sensitivity required for in-vivo trace element detection in the breast at the lowest possible patient dose levels. Our final goal is to implement a portable, low-dose tomographic screening system for breast cancer which does not require breast compression or invasive biopsies.

Elemental spectrum of a mouse obtained via neutron stimulation

Several studies have shown that the concentration of certain elements may be a disease indicator. We are developing a spectroscopic imaging technique, Neutron Stimulated Emission Computed Tomography (NSECT), to non-invasively measure and image elemental concentrations within the body. The region of interest is interrogated via a beam of high-energy neutrons that excite elemental nuclei through inelastic scatter. These excited nuclei then relax by emitting characteristic gamma radiation. Acquiring the gamma energy spectrum in a tomographic geometry allows reconstruction of elemental concentration images. Our previous studies have demonstrated NSECTs ability to obtain spectra and images of known elements and phantoms, as well as, initial interrogations of biological tissue. Here, we describe the results obtained from NSECT interrogation of a fixed mouse specimen. The specimen was interrogated via a 5MeV neutron beam for 9.3 hours in order to ensure reasonable counting statistics. The gamma energy spectrum was obtained using two High-Purity Germanium (HPGe) clover detectors. A background spectrum was obtained by interrogating a specimen container containing 50mL of 0.9% NaCl solution. Several elements of biological interest including 12C, 40Ca, 31P, and 39K were identified with greater then 90% confidence. This interrogation demonstrates the feasibility of NSECT interrogation of small animals. Interrogation with a commercial neutron source that provides higher neutron flux and lower energy (~2.5MeV) neutrons would reduce scanning time and eliminate background from certain elements.