Robert Z. Stodilka

3D photoacoustic imaging

Our group has concentrated on development of a 3D photoacoustic imaging system for biomedical imaging research. The technology employs a sparse parallel detection scheme and specialized reconstruction software to obtain 3D optical images using a single laser pulse. With the technology we have been able to capture 3D movies of translating point targets and rotating line targets. The current limitation of our 3D photoacoustic imaging approach is its inability ability to reconstruct complex objects in the field of view. This is primarily due to the relatively small number of projections used to reconstruct objects. However, in many photoacoustic imaging situations, only a few objects may be present in the field of view and these objects may have very high contrast compared to background. That is, the objects have sparse properties. Therefore, our work had two objectives: (i) to utilize mathematical tools to evaluate 3D photoacoustic imaging performance, and (ii) to test image reconstruction algorithms that prefer sparseness in the reconstructed images. Our approach was to utilize singular value decomposition techniques to study the imaging operator of the system and evaluate the complexity of objects that could potentially be reconstructed. We also compared the performance of two image reconstruction algorithms (algebraic reconstruction and l1-norm techniques) at reconstructing objects of increasing sparseness. We observed that for a 15-element detection scheme, the number of measureable singular vectors representative of the imaging operator was consistent with the demonstrated ability to reconstruct point and line targets in the field of view. We also observed that the l1-norm reconstruction technique, which is known to prefer sparseness in reconstructed images, was superior to the algebraic reconstruction technique. Based on these findings, we concluded (i) that singular value decomposition of the imaging operator provides valuable insight into the capabilities of a 3D photoacoustic imaging system, and (ii) that reconstruction algorithms which favor sparseness can significantly improve imaging performance. These methodologies should provide a means to optimize detector count and geometry for a multitude of 3D photoacoustic imaging applications.

The relative contributions of scatter and attenuation corrections toward improved brain SPECT quantification.

Mounting evidence indicates that scatter and attenuation are major confounds to objective diagnosis of brain disease by quantitative SPECT. There is considerable debate, however, as to the relative importance of scatter correction (SC) and attenuation correction (AC), and how they should be implemented. The efficacy of SC and AC for 99mTc brain SPECT was evaluated using a two-compartment fully tissue-equivalent anthropomorphic head phantom. Four correction schemes were implemented: uniform broad-beam AC, non-uniform broad-beam AC, uniform SC + AC, and non-uniform SC + AC. SC was based on non-stationary deconvolution scatter subtraction, modified to incorporate a priori knowledge of either the head contour (uniform SC) or transmission map (non-uniform SC). The quantitative accuracy of the correction schemes was evaluated in terms of contrast recovery, relative quantification (cortical:cerebellar activity), uniformity ((coefficient of variation of 230 macro-voxels) x 100%), and bias (relative to a calibration scan). Our results were: uniform broad-beam (mu = 0.12 cm(-1)) AC (the most popular correction): 71% contrast recovery, 112% relative quantification, 7.0% uniformity, +23% bias. Non-uniform broad-beam (soft tissue mu = 0.12 cm(-1)) AC: 73%, 114%, 6.0%, +21%, respectively. Uniform SC + AC: 90%, 99%, 4.9%, +12%, respectively. Non-uniform SC + AC: 93%, 101%, 4.0%, +10%, respectively. SC and AC achieved the best quantification; however, non-uniform corrections produce only small improvements over their uniform counterparts. SC + AC was found to be superior to AC; this advantage is distinct and consistent across all four quantification indices.

Tracking transplanted cells using dual-radionuclide SPECT

The purpose of this study was to characterize the performance of single photon emission computed tomography (SPECT) in tasks associated with tracking transplanted cells. Previous studies identified matters of hardware design, whereas we focus on biological variables impacting system performance, such as cell colony growth and non-specific radiolabelling. Using experimental data, a digital phantom was developed of in vitro 111In-radiolabelled stem cells, transfected with a reporter gene, transplanted into canine infarcted myocardium and interrogated using a peripherally injected 131I-radiolabelled reporter probe. Single- and dual-head SPECT acquisition was simulated. Performance was characterized using an estimation task, where the precision of parameter estimates (111In and 131I radiolabel quantity, cell colony size and location, and background) was tracked as the phantom evolved to simulate 111In-label efflux, cell colony growth and improved reporter probe specificity. In vitro pre-labelling of transplanted cells improved precision of parameter estimates via a priori size and location information. Precision of radiolabel quantity estimates improved with cell colony growth, despite 111In radiolabel dilution; size and location parameters were influenced little. Precision of radiolabel quantity estimates improved with reduced reporter probe non-specific uptake. The performance of SPECT in cell tracking is influenced strongly by biological variables. These should be considered when planning experiments or developing SPECT technology for cell tracking.

The detection threshold for extremely low frequency magnetic fields may be below 1000 nT-Hz in mice.

Previous experiments with mice have shown that a repeated 1 h daily exposure to an ambient magnetic field shielded environment induces analgesia (anti-nociception). This shielding reduces ambient static and extremely low frequency magnetic fields (ELF-MF) by approximately 100 times for frequencies below 120 Hz. To determine the threshold of ELF-MF amplitude that would attenuate or abolish this effect, 30 and 120 Hz magnetic fields were introduced into the shielded environment at peak amplitudes of 25, 50, 100 and 500 nT. At 30 Hz, peak amplitudes of 50, 100, and 500 nT attenuated this effect in proportion to the amplitude magnitude. At 120 Hz, significant attenuation was observed at all amplitudes. Exposures at 10, 60, 100, and 240 Hz with peak amplitudes of 500, 300, 500, and 300 nT, respectively, also attenuated the induced analgesia. No exposure abolished this effect except perhaps at 120 Hz, 500 nT. If the peak amplitude frequency product was kept constant at 6000 nT-Hz for frequencies of 12.5, 25, 50, and 100 Hz, the extent of attenuation was constant, indicating that the detection mechanism is dependent on the nT-Hz product. A plot of effect versus the induced current metric nT-Hz suggests a threshold of ELF-MF detection in mice at or below 1000 nT-Hz.

Comparison of the myocardial clearance of endothelial progenitor cells injected early versus late into reperfused or sustained occlusion myocardial infarction

Stem cell transplantation following AMI has shown promise for the repair or reduction of the amount of myocardial injury. There is some evidence that these treatment effects appear to be directly correlated to cell residence time. This study aims to assess the effects of (a) the timing of stem cell injection following myocardial infarction, and (b) flow milieu, on cell residence times at the site of transplantation by comparing three time points (day of infarction, week 1 and week 4–5), and two models of acute myocardial infarction (sustained occlusion or reperfusion). Twenty-one dogs received 2 injections of 30 million endothelial progenitor cells. The first injections were administered by epicardial (nxa0=xa08) or endocardial injection (nxa0=xa013) either on the day of infarction (nxa0=xa015) or at 1xa0week (nxa0=xa06). The second injections were administered by only endocardial injection (nxa0=xa018) 4xa0weeks following the first injection. Cell clearance half-lives were comparable between early and late injections. However, transplants into sustained occlusion infarcts resulted in slower cell clearance 77.1xa0±xa06.1 (nxa0=xa018) versus reperfused 59.4xa0±xa02.9xa0h (nxa0=xa021) pxa0=xa00.009. Sustained occlusion infarcts had longer cell retention in comparison to reperfusion whereas the timing of injection did not affect clearance rates. If the potential for myocardial regeneration associated with cell transplantation is, at least in part, linked to cell residence times, then greater benefit may be observed with transplants into infarcts associated with persistent coronary artery occlusion.

A comparison of MR-based attenuation correction in PET versus SPECT

Attenuation correction (AC) is a critical step in the reconstruction of quantitatively accurate positron emission tomography (PET) and single photon emission computed tomography (SPECT) images. Several groups have proposed magnetic resonance (MR)-based AC algorithms for application in hybrid PET/MR systems. However, none of these approaches have been tested on SPECT data. Since SPECT/MR systems are under active development, it is important to ascertain whether MR-based AC algorithms validated for PET can be applied to SPECT. To investigate this issue, two imaging experiments were performed: one with an anthropomorphic chest phantom and one with two groups of canines. Both groups of canines were imaged from neck to abdomen, one with PET/CT and MR (n = 4) and the other with SPECT/CT and MR (n = 4), while the phantom was imaged with all modalities. The quality of the nuclear medicine reconstructions using MR-based attenuation maps was compared between PET and SPECT on global and local scales. In addition, the sensitivity of these reconstructions to variations in the attenuation map was ascertained. On both scales, it was found that the SPECT reconstructions were of higher fidelity than the PET reconstructions. Further, they were less sensitive to changes to the MR-based attenuation map. Thus, MR-based AC algorithms that have been designed for PET/MR can be expected to demonstrate improved performance when used for SPECT/MR.

The response of the human circulatory system to an acute 200-μT, 60-Hz magnetic field exposure

PurposeRecent research by the authors on the effects of extremely low-frequency (ELF) magnetic field (MF) exposure on human heart rate (HR), heart rate variability (HRV), and skin blood perfusion found no cardiovascular effects of exposure to an 1,800-μT, 60-Hz MF. Research from our group using rats, however, has suggested a microcirculatory response to a 200-μT, 60-Hz MF exposure. The present pilot study investigated the effects of 1xa0h of exposure to a 200-μT, 60-Hz MF on the human circulation. Microcirculation (as skin blood perfusion) and HR were measured using laser Doppler flowmetry. Mean arterial pressure was monitored with a non-invasive blood pressure system.MethodsTen volunteers were recruited to partake in a counterbalanced, single-blinded study consisting of two testing sessions (real and sham exposure) administered on separate days. Each session included four consecutive measurement periods separated by rest, allowing assessment of cumulative and residual MF effects.ResultsA within-subjects analysis of variance did not reveal session by time period interactions for any of the parameters which would have been suggestive of a MF effect (pxa0>xa00.05). Perfusion, HR, and skin surface temperature decreased over the course of the experiment (pxa0<xa00.05).ConclusionsThe MF used in this experiment did not affect perfusion, HR, or mean arterial pressure. Decreasing perfusion and HR trends over time were similar to our previous results and appear to be associated with a combination of inactivity (resulting in decreasing body temperatures) and reduced physiological arousal.

Analysis of a photoacoustic imaging system by singular value decomposition

Photoacoustic imaging is a hybrid imaging modality capable of producing contrast similar to optical imaging techniques but with increased penetration depth and resolution in turbid media by encoding the information as acoustic waves. In general, it is important to characterize system performance by parameters such as sensitivity, resolution, and contrast. However, system characterization can extend beyond these metrics by implementing advanced analysis via singular value decomposition. A method was developed to experimentally measure a matrix that represented the imaging operator for the system. Analysis of the imaging operator was done via singular value decomposition so that the capability of the system to reconstruct objects and the inherent system sensitivity to those objects could be understood. The results provided by singular value decomposition were compared to simulations performed on an ideal system with matching transducer arrangement and defined object space.

Method for imaging quantum dots during exposure to gamma radiation

Quantum dots have been used in a wide variety of biomedical applications. A key advantage of these particles is that their optical properties depend predictably on size, which enables tuning of the emission wavelength. Recently, it was found that CdSe/ZnS quantum dots lose their ability to photoluminescence after exposure to gamma radiation (J. Phys. Chem. C., 113: 2580-2585 (2009). A method for readout of the loss of quantum dot photoluminescence during exposure to radiation could enable a multitude of real-time dosimetry applications. Here, we report on a method to image photoluminescence from quantum dots from a distance and under ambient lighting conditions. The approach was to construct and test a time-gated imaging system that incorporated pulsed illumination. The system was constructed from a pulsed green laser (Nd:YAG, 20 pulses/s, 5 ns pulse duration, ~5 mJ/pulse), a time-gated camera (LaVision Picostar, 2 ns gate width), and optical components to enable coaxial illumination and imaging. Using the system to image samples of equivalent concentration to the previous end-point work, quantum dot photoluminescence was measureable under ambient room lighting at a distance of 25 cm from the sample with a signal to background of 7.5:1. Continuous exposure of samples to pulsed laser produced no measureable loss of photoluminescence over a time period of one hour. With improvements to the light collection optics the range of the system is expected to increase to several metres, which will enable imaging of samples during exposure to a gamma radiation source.

Characterization of sparse-array detection photoacoustic tomography using the singular value decomposition

A photoacoustic tomography (PAT) method that employs a sparse two-dimentional (2D) array of detector elements has recently been employed to reconstruct images of simple objects from highly incomplete measurement data. However, there remains an important need to understand what type of object features can be reliably reconstructed from such a system. In this work, we numerically compute the singular value decomposition (SVD) of different system matrices that are relevant to implementations of sparse-array PAT. For a given number and arrangement of measurement transducers, this will reveal the type of object features that can reliably be reconstructed as well as those that are invisible to the imaging system.