Greeshma A. Agasthya

Detection of iron overload through neutron stimulated emission computed tomography: a sensitivity analysis study

Neutron stimulated emission computed tomography (NSECT) is being developed as a non-invasive technique to diagnose iron overload in the liver. It uses inelastic scatter interactions between fast neutrons and iron nuclei to quantify localized distributions of iron within the liver. Preliminary studies have demonstrated the feasibility of iron overload detection through NSECT using a Monte-Carlo simulation model in GEANT4. The work described here uses the GEANT4 simulation model to analyze iron-overload detection sensitivity in NSECT. A simulation of a clinical NSECT system was designed in GEANT4. Simulated models were created for human liver phantoms with concentrations of iron varying from 0.5 mg/g to 20 mg/g (wet). Each liver phantom was scanned with 100 million neutron events to generate gamma spectra showing gamma-lines corresponding to iron in the liver. A background spectrum was obtained using a water phantom of equal mass as the liver phantom and was subtracted from each liver spectrum. The height of the gamma line at 847 keV (corresponding to 56Fe) was used as a measure of the detected iron concentration in each background-corrected spectrum. The variation in detected gamma counts was analyzed and plotted as a function of the liver iron concentration to quantify measurement error. Analysis of the differences between the measured and expected value of iron concentration indicate that NSECT sensitivity for detection of iron in liver tissue may lie in the range of 0.5 mg/g - 1 mg/g, which represents a clinically significant range for iron overload detection in humans.

Simulations of Breast Cancer Imaging Using Gamma-Ray Stimulated Emission Computed Tomography

Here, we present an innovative imaging technology for breast cancer using gamma-ray stimulated spectroscopy based on the nuclear resonance fluorescence (NRF) technique. In NRF, a nucleus of a given isotope selectively absorbs gamma rays with energy exactly equal to one of its quantized energy states, emitting an outgoing gamma ray with energy nearly identical to that of the incident gamma ray. Due to its application of NRF, gamma-ray stimulated spectroscopy is sensitive to trace element concentration changes, which are suspected to occur at early stages of breast cancer, and therefore can be potentially used to noninvasively detect and diagnose cancer in its early stages. Using Monte-Carlo simulations, we have designed and demonstrated an imaging system that uses gamma-ray stimulated spectroscopy for visualizing breast cancer. We show that gamma-ray stimulated spectroscopy is able to visualize breast cancer lesions based primarily on the differences in the concentrations of trace elements between diseased and healthy tissue, rather than differences in density that are crucial for X-ray mammography. The technique shows potential for early breast cancer detection; however, improvements are needed in gamma-ray laser technology for the technique to become a clinically feasible method of detecting and diagnosing cancer at early stages.

Sensitivity analysis for liver iron measurement through neutron stimulated emission computed tomography: a Monte Carlo study in GEANT4.

Neutron stimulated emission computed tomography (NSECT) is being developed as a non-invasive imaging modality to detect and quantify iron overload in the human liver. NSECT uses gamma photons emitted by the inelastic interaction between monochromatic fast neutrons and iron nuclei in the body to detect and quantify the disease. Previous simulated and physical experiments with phantoms have shown that NSECT has the potential to accurately diagnose iron overload with reasonable levels of radiation dose. In this work, we describe the results of a simulation study conducted to determine the sensitivity of the NSECT system for hepatic iron quantification in patients of different sizes. A GEANT4 simulation of the NSECT system was developed with a human liver and two torso sizes corresponding to small and large patients. The iron concentration in the liver ranged between 0.5 and 20 mg g(-1), corresponding to clinically reported iron levels in iron-overloaded patients. High-purity germanium gamma detectors were simulated to detect the emitted gamma spectra, which were background corrected using suitable water phantoms and analyzed to determine the minimum detectable level (MDL) of iron and the sensitivity of the NSECT system. These analyses indicate that for a small patient (torso major axis = 30 cm) the MDL is 0.5 mg g(-1) and sensitivity is ∼13 ± 2 Fe counts/mg/mSv and for a large patient (torso major axis = 40 cm) the values are 1 mg g(-1) and ∼5 ± 1 Fe counts/mg/mSv, respectively. The results demonstrate that the MDL for both patient sizes lies within the clinically significant range for human iron overload.

Locating stored iron in the liver through attenuation measurement in NSECT

Neutron stimulated emission computed tomography (NSECT) is a quantitative spectroscopic technique to detect element concentrations in the body. In previous work, we have demonstrated the ability to detect non-uniform distributions of iron overload in liver (in hemochromatosis) with a sensitivity of approximately 5mg/g. The diagnosis of hemochromatosis is performed by detecting characteristic gamma photons emitted by iron nuclei after they undergo inelastic scatter with incident neutrons. The efficiency of detection of the gamma photons is a combination of the attenuation of neutrons passing through the body and the attenuation of gamma photons before reaching the detectors. With non-uniform iron distributions, therefore, the resulting total attenuation depends on the position of the iron store within the body with respect to the neutron beam and the gamma detectors. We are developing an attenuation correction technique which takes into consideration the position of the iron-store in the liver to compute a correction factor based on a combination of neutron and gamma attenuation. In this work we present results from a Monte-Carlo simulation study exploring the effect of the location of the iron-store within the liver. The NSECT scanning geometry used for data collection was simulated in GEANT4 [1]. A lesion of iron was placed at different locations within the liver and scanned to obtain an estimate of the detected signal. An estimate of the unattenuated signal was obtained and used to determine the total attenuation in the liver tissue. The attenuation profile was obtained for each position of the lesion and compared against a theoretical value. The results were found to be in agreement with each other, indicating that a theoretically calculated attenuation profile can be accurately used to create attenuation maps and hence locate iron-stores in the liver using NSECT.

CT Breast Dose Reduction with the Use of Breast Positioning and Organ-Based Tube Current Modulation

Purpose: This study aimed to investigate the breast dose reduction potential of a breast‐positioning (BP) technique for thoracic CT examinations with organ‐based tube current modulation (OTCM). Methods: This study included 13 female anthropomorphic computational phantoms (XCAT, age range: 27–65 y.o., weight range: 52–105.8 kg). Each phantom was modified to simulate three breast sizes in standard supine geometry. The modeled breasts were then morphed to emulate BP that constrained the majority of the breast tissue inside the 120° anterior tube current (mA) reduction zone. The OTCM mA value was modeled using a ray‐tracing program, which reduced the mA to 20% in the anterior region with a corresponding increase to the posterior region. The organ doses were estimated by a validated Monte Carlo program for a typical clinical CT system (SOMATOM Definition Flash, Siemens Healthcare). The simulated organ doses and organ doses normalized by CTDIvol were used to compare three CT protocols: attenuation‐based tube current modulation (ATCM), OTCM, and OTCM with BP (OTCMBP). Results: On average, compared to ATCM, OTCM reduced breast dose by 19.3 ± 4.5%, whereas OTCMBP reduced breast dose by 38.6 ± 8.1% (an additional 23.8 ± 9.4%). The dose saving of OTCMBP was more significant for larger breasts (on average 33, 38, and 44% reduction for 0.5, 1, and 2 kg breasts, respectively). Compared to ATCM, OTCMBP also reduced thymus and heart dose by 15.1 ± 7.4% and 15.9 ± 6.2% respectively. Conclusions: In thoracic CT examinations, OTCM with a breast‐positioning technique can markedly reduce unnecessary exposure to radiosensitive organs in anterior chest wall, specifically breast tissue. The breast dose reduction is more notable for women with larger breasts.

3D element imaging using NSECT for the detection of renal cancer: a simulation study in MCNP

This work describes a simulation study investigating the application of neutron stimulated emission computed tomography (NSECT) for noninvasive 3D imaging of renal cancer in vivo. Using MCNP5 simulations, we describe a method of diagnosing renal cancer in the body by mapping the 3D distribution of elements present in tumors using the NSECT technique. A human phantom containing the kidneys and other major organs was modeled in MCNP5. The element composition of each organ was based on values reported in literature. The two kidneys were modeled to contain elements reported in renal cell carcinoma (RCC) and healthy kidney tissue. Simulated NSECT scans were executed to determine the 3D element distribution of the phantom body. Elements specific to RCC and healthy kidney tissue were then analyzed to identify the locations of the diseased and healthy kidneys and generate tomographic images of the tumor. The extent of the RCC lesion inside the kidney was determined using 3D volume rendering. A similar procedure was used to generate images of each individual organ in the body. Six isotopes were studied in this work - (32)S, (12)C, (23)Na, (14)N, (31)P and (39)K. The results demonstrated that through a single NSECT scan performed in vivo, it is possible to identify the location of the kidneys and other organs within the body, determine the extent of the tumor within the organ, and to quantify the differences between cancer and healthy tissue-related isotopes with p ≤ 0.05. All of the images demonstrated appropriate concentration changes between the organs, with some discrepancy observed in (31)P, (39)K and (23)Na. The discrepancies were likely due to the low concentration of the elements in the tissue that were below the current detection sensitivity of the NSECT technique.

Neutron time-of-flight spectroscopy for depth-resolved quantification through NSECT

With advances in detector technology, gamma-ray detectors are now capable of reporting both time of arrival of a photon and its energy. Although the gamma energies detected from the inelastic scattering of neutrons with elemental nuclei in the tissue of interest are being exploited in Neutron Stimulation Emission Computed Tomography (NSECT) to detect different elemental disorders, the timing information is largely ignored. Here we present a technique to utilize the time of arrival of gamma photons at a detector to locate focal liver lesions in diseases such as hemochromatosis and liver cancer. A GEANT4 simulation of 5-MeV neutrons was used to irradiate a liver phantom with multiple lesions with different iron concentrations. The time of arrival of gamma photons from neutron-56Fe inelastic scatter was recorded using a 360 degree, 100% efficient detection system and used to locate the lesions in the beam path. The resulting spectra were resolved in nanosecond time bins (corresponding to the expected arrival time of inelastic-scatter gamma photons from the lesion) and clearly demonstrated the ability to localize the focal liver lesions through neutron time-of-flight (TOF) spectroscopy. The preliminary results showed errors of only 10–20% in lesion position, demonstrating the strong potential of the technique.

Quantitative elemental imaging with neutrons for breast cancer diagnosis: A GEANT4 study

Neutron stimulated emission computed tomography (NSECT) has been proposed as an early cancer-detection technique with the capability of 3-D tomographic imaging for identification of malignant tumors. In previous work we have demonstrated the ability of the technique to differentiate between normal and malignant breast tumors based on the concentration of cancer-marking elements in the tissue. Here we present tomographic images from a breast phantom with benign and malignant tumors simulated in GEANT4. A simulated model of the NSECT system was developed in GEANT4, along with phantoms corresponding to the human breast with benign and malignant tumors. Each tumor within the breast was given a different concentration of cancer-marking trace elements based on values reported in literature. The phantom was scanned with a 5-MeV neutron beam over a 180-degree angle. Tomographic images were reconstructed for six elements of interest from 10 different spectral lines. The results showed excellent agreement between the location of the tumor and the concentration of trace element detected in gamma lines from bromine, cesium, sodium and zinc. These results demonstrate the ability of NSECT in quantitative elemental imaging for breast cancer detection.

Neutron stimulated emission computed tomography for brain cancer imaging

Neutron stimulated emission computed tomography (NSECT) uses photons emitted from inelastic scattering of neutrons with biological objects to quantify the elemental composition of the object and reconstruct an image. Previously, NSECT has been used to detect liver and breast disease in vivo. In this study, we investigated the capability of imaging brain tumors using NSECT. A GEANT4 simulation was developed to model the brain, skull, and a spherical lesion. Images corresponding to phosphorus, sulfur, and iron (both individually and as combinations) were generated from a simulated NSECT scan. Signal-to-noise ratio (SNR) and full width at half maximum (FWHM) in the tumor region were calculated to assess image accuracy (FWHM ≤ 5% error) and detectability (SNR > 2.5). The scan with the least amount of absorbed dose required to achieve these criteria was defined as the optimal acquisition. The lowest dose value was found to be 0.0837 cGy for a 2 cm brain tumor imaged using a single germanium detector, 6 equally spaced angles from 0 to 180 degrees, 20 projections per angle and 0.5 million neutrons per projection. The SNR for the combination of phosphorus, sulfur, and iron with the given condition was 9.288 and FWHM for the iron was 15 mm with the given condition. In conclusion, NSECT is capable of imaging a 2 cm brain tumor using the elemental composition of phosphorus, sulfur, and iron with reasonable SNR, FWHM and radiation dose.

Nuclear resonance fluorescence (NRF) in GEANT4: Development, validation, and testing

Despite its utility and applicability, the ability to simulate the NRF technique is not currently included in GEANT4. Here we describe the development, validation and testing of NRF in GEANT4 for 10 separate isotopes. An NRF class named G4NRF was developed to handle NRF physics. Validation of the simulation was performed by benchmarking it against experimental measurements for measured counts from gamma-ray scattering in water and metallic samples. The validation results show agreement between the simulation and experimental spectra for the appearance of the NRF peak. We have begun applying the NRF simulation for medical research, and we are seeking to make the NRF physics code available to the GEANT4 community in a future release.