Singular value decomposition analysis of a photoacoustic imaging system and 3D imaging at 0.7 FPS.

Photoacoustic imaging is a non-ionizing imaging modality that provides contrast consistent with optical imaging techniques while the resolution and penetration depth is similar to ultrasound techniques. In a previous publication [Opt. Express 18, 11406 (2010)], a technique was introduced to experimentally acquire the imaging operator for a photoacoustic imaging system. While this was an important foundation for future work, we have recently improved the experimental procedure allowing for a more densely populated imaging operator to be acquired. Subsets of the imaging operator were produced by varying the transducer count as well as the measurement space temporal sampling rate. Examination of the matrix rank and the effect of contributing object space singular vectors to image reconstruction were performed. For a PAI system collecting only limited data projections, matrix rank increased linearly with transducer count and measurement space temporal sampling rate. Image reconstruction using a regularized pseudoinverse of the imaging operator was performed on photoacoustic signals from a point source, line source, and an array of point sources derived from the imaging operator. As expected, image quality increased for each object with increasing transducer count and measurement space temporal sampling rate. Using the same approach, but on experimentally sampled photoacoustic signals from a moving point-like source, acquisition, data transfer, reconstruction and image display took 1.4 s using one laser pulse per 3D frame. With relatively simple hardware improvements to data transfer and computation speed, our current imaging results imply that acquisition and display of 3D photoacoustic images at laser repetition rates of 10Hz is easily achieved.

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.

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

PURPOSE: Recent 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 1 h 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. METHODS: Ten 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. RESULTS: A 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 (p > 0.05). Perfusion, HR, and skin surface temperature decreased over the course of the experiment (p < 0.05). CONCLUSIONS: The 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.

Hiatal hernia after robotic-assisted coronary artery bypass graft surgery.

BACKGROUND: The aim of the present study is to determine the incidence/progression of hiatal hernia (HH) after robotic-assisted coronary artery bypass grafting (RA-CABG) surgery. METHODS: We reviewed the pre- and post-operative computed tomography (CT) of 491 patients who underwent RA-CABG between 2000 and 2017. Post-operative CT was acquired prospectively in a research protocol. CT was reviewed to assess the presence and the size of HH. RESULTS: We found 444/491 (90.4%) had pre-operative CT, while 201/491 (40.9%) had post-operative CT. In total, 155/491 (31.6%) had both pre- and long-term post-operative CT with a mean follow-up of 6.2 (±3.5) years. HH was more prevalent on post-operative CT, 64/155 (41.3%) compared to pre-operative CT, 44/155 (28.4%), P<0.0001. The diameter of pre-existing HH 2.8 (±1.8) cm was significantly greater after surgery 3.9 (±2.5) cm, P<0.0001. As well the volume of the pre-existing HH 5.8 (4.4-9.2) mL (quartile) was significantly greater after surgery 14.1 (7.2-64.9) mL, P<0.0001. 20/155 (12.9%) had a newly developed HH after RA-CABG. A binary multivariate regression including HH risk factors showed that male gender is a predictor of developing a HH after RA-CABG with Hazard Ratio of 3.038, confidence interval (1.10-8.43), P=0.033. CONCLUSIONS: RA-CABG is associated with an increased risk of developing HH and increases the size of pre-existing HH.

Analysis of a photoacoustic imaging system by the crosstalk matrix and 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 the performance of a photoacoustic imaging system by parameters such as sensitivity, resolution, and contrast. However, system characterization can extend beyond these metrics by implementing advanced analysis via the crosstalk matrix and singular value decomposition. A method was developed to experimentally measure a matrix that represented the imaging operator for a photoacoustic imaging system. Computations to produce the crosstalk matrix were completed to provide insight into the spatially dependent sensitivity and aliasing for the photoacoustic imaging system. Further analysis of the imaging operator was done via singular value decomposition to estimate the capability of the imaging system to reconstruct objects and the inherent sensitivity to those objects. The results provided by singular value decomposition were compared to SVD results from a de-noised imaging operator to estimate the number of measurable singular vectors for the system. These characterization techniques can be broadly applied to any photoacoustic system and, with regards to the studied system, could be used as a basis for improvements to future iterations.

In vivo SPECT quantification of transplanted cell survival after engraftment using (111)In-tropolone in infarcted canine myocardium.

UNLABELLED: Current investigations of cell transplant therapies in damaged myocardium are limited by the inability to quantify cell transplant survival in vivo. We describe how the labeling of cells with (111)In can be used to monitor transplanted cell viability in a canine infarction model. METHODS: We experimentally determined the contribution of the (111)In signal associated with transplanted cell (TC) death and radiolabel leakage to the measured SPECT signal when (111)In-labeled cells were transplanted into the myocardium. Three groups of experiments were performed in dogs. Radiolabel leakage was derived by labeling canine myocardium in situ with free (111)In-tropolone (n = 4). To understand the contribution of extracellular (111)In (e.g., after cell death), we developed a debris impulse response function (DIRF) by injecting lysed (111)In-labeled cells within reperfused (n = 3) and nonreperfused (n = 5) myocardial infarcts and within normal (n = 3) canine myocardium. To assess the application of the modeling derived from these experiments, (111)In-labeled cells were transplanted into infarcted myocardium (n = 4; 3.1 x 10(7) +/- 5.4 x 10(6) cells). Serial SPECT images were acquired after direct epicardial injection to determine the time-dependent radiolabel clearance. Clearance kinetics were used to correct for (111)In associated with viable TCs. RESULTS: (111)In clearance followed a biphasic response and was modeled as a biexponential with a short (T(1/2)(s)) and long (T(1/2)(l)) biologic half-life. The T(1/2)(s) was not significantly different between experimental groups, suggesting that initial losses were due to transplantation methodology, whereas the T(1/2)(l) reflected the clearance of retained (111)In. DIRF had an average T(1/2)(l) of 19.4 +/- 4.1 h, and the T(1/2)(l) calculated from free (111)In-tropolone injected in situ was 882.7 +/- 242.8 h. The measured T(1/2)(l) for TCs was 74.3 h and was 71.2 h when corrections were applied. CONCLUSION: A new quantitative method to assess TC survival in myocardium using SPECT and (111)In has been introduced. At the limits, method accuracy is improved if appropriate corrections are applied. In vivo (111)In imaging most accurately describes cell viability half-life if T(1/2)(l) is between 20 h and 37 d.

Technical Note: Comparison of megavoltage, dual-energy, and single-energy CT-based µ-maps for a four-channel breast coil in PET/MRI.

PURPOSE: The purpose of this study was to describe and evaluate methods for calculating a megavoltage computed tomography (MVCT)-derived MR hardware attenuation map (µ-map) and dual-energy CT (DECT) for 511 keV photons. METHODS: Phantom measurements were acquired on a whole-body hybrid PET/MRI system, using a four-channel receive-only MR radiofrequency (RF) breast coil. Two acquisitions were performed: with the phantoms positioned in the four-channel RF breast coil, and without the breast coil. PET attenuation from the breast coil was corrected using three different CT-derived hardware µ-maps: (a) Single-energy CT (SECT), (b) DECT, and (c) MVCT. Each attenuation-corrected (AC) PET volume was evaluated and compared with the acquisition performed without the breast coil. RESULTS: The breast coil attenuated PET photons by 10% overall. Threshold values were applied to the SECT µ-map to reduce the effects of metal artifacts, but overcorrection occurred in more highly attenuated regions. The DECT-derived virtual monochromatic image reduced beam-hardening artifacts, but other metal artifacts remained. Despite the remaining metal artifacts in the DECT image, it led to an improvement in the more attenuated regions. The MVCT images appear to be free from metal artifacts leading to an artifact-free µ-map and a further improvement AC-PET images. CONCLUSIONS: Our MVCT-based approach for creating µ-maps for MR RF coils greatly reduces artifacts produced by metal in a SECT approach. This eliminates the need for other artifact reduction methods, including the application of a threshold of narrow beam attenuation coefficients, or disassembling hardware to remove high-Z components before imaging with a kilovoltage source.

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.

A method for quantitative cell tracking using SPECT for the evaluation of myocardial stem cell therapy.

PURPOSE: A promising SPECT-based method for evaluating stem cells therapy uses (111)In-labelled cells, transfected with a reporter gene. Cells are first transplanted to the infarct, and subsequently interrogated for transgenic expression using a systemic injection of an (131)I-labelled reporter probe. The method is impeded by the physical effects of scatter, (131)I/(111)In cross-talk, and attenuation. We hypothesize that correcting for physical effects improves detection of transgenic expression in transplanted cells when (111)In localization is available. METHODS: Canine bone marrow mesenchymal cells (BMMCs), radiolabelled and transfected, were injected into infarcted myocardium. Next, a reporter probe was injected systemically, and 22 SPECT scans were acquired over 20 h. Finally, (99m)Tc-sestamibi was injected and imaged. The animal was killed, the heart sectioned, and counted for (131)I and (111)In in a well-counter ('gold standard'). Canine SPECTs were reconstructed in two ways: with corrections for physical effects and without corrections. The first (111)In reconstruction and the (99m)Tc reconstruction were used to define volumes-of-interest over the transplanted BMMC (VBMMC) and normal myocardium (VNM), respectively. RESULTS: (131)I reconstructions without corrections for physical effects had negligible differential uptake. With corrections, VBMMC was consistently higher than VNM, demonstrating transgene expression. (131)I had the following VBMMC:VNM activity ratio: without correction for physical effects=0.869; with corrections=1.23; and well-counter=1.21. VNM showed the following (131)I:(111)In activity ratio: without corrections=3.07; with corrections=1.38; and well-counter=1.58. CONCLUSIONS: In dual-isotope SPECT, corrections for physical effects were required to detect transgene expression in cells transplanted into an infarction when localization information was available.

Characterization of tomographic sampling in hybrid PET using the Fourier crosstalk matrix.

Hybrid positron emission tomography (PET) cameras can be used to measure the distribution of positron emitting radionuclides. An important system parameter for Hybrid PET is the appropriate tomographic sampling requirements. In this paper, a previously developed theoretical formulation for quantifying sampling in continuous-to-discrete tomographic systems, termed the "crosstalk matrix," is used to provide information on the recoverability of the Fourier coefficients that represent the continuous object. In addition, the crosstalk matrix can be related to image quality assessment. Here, we use the crosstalk matrix to evaluate tomographic sampling for Hybrid PET systems. Dual-and triple-head systems were compared, with emphasis placed on studying how system performance changes as the number of gantry stops is increased, and as the line-of-response acceptance angle is reduced. Examination of the crosstalk matrix, as well as figures-of-merit measuring task performance that are computed using the crosstalk matrix, show that increasing angular sampling improves Fourier coefficient recoverability and reduces aliasing.

Description and assessment of a registration-based approach to include bones for attenuation correction of whole-body PET/MRI.

PURPOSE: Attenuation correction for whole-body PET/MRI is challenging. Most commercial systems compute the attenuation map from MRI using a four-tissue segmentation approach. Bones, the most electron-dense tissue, are neglected because they are difficult to segment. In this work, the authors build on this segmentation approach by adding bones using a registration technique and assessing its performance on human PET images. METHODS: Twelve oncology patients were imaged with FDG PET/CT and MRI using a Turbo-FLASH pulse sequence. A database of 121 attenuation correction quality CT scans was also collected. Each patient MRI was compared to the CT database via weighted heuristic measures to find the "most similar" CT in terms of body geometry. The similar CT was aligned to the MRI with a deformable registration method. Two MRI-based attenuation maps were computed. One was a standard four-tissue segmentation (air, lung, fat, and lean tissue) using basic image processing techniques. The other was identical, except the bones from the aligned CT were added. The PET data were reconstructed with the patient's CT-based attenuation map (the silver standard) and both MRI-based attenuation maps. The relative errors of the MRI-based attenuation corrections were computed in 14 standardized volumes of interest, in lesions, and over whole tissues. The squared Pearson correlation coefficient was also calculated over whole tissues. Statistical testing was done with ANOVAs and paired t-tests. RESULTS: The MRI-based attenuation correction ignoring bone had relative errors ranging from -37% to -8% in volumes of interest containing bone. By including bone, the magnitude of the relative error was reduced in all cases (p<0.001), ranging from -3% to 4%. Further, the relative error in volumes of interest adjacent to bone was improved from a mean of -7.5% to 2% (p<0.001). In the other seven volumes of interest, including bone reduced the magnitude of relative error in three cases (p<0.001), had no effect in three cases, and increased relative error in one case. There was no statistically significant difference in the relative error in lesions. Over whole tissues, including bone slightly increased relative error in lung from 7.7% to 8.0% (p=0.002), in fat from 8.5% to 9.2% (p<0.001), and in lean tissue from -2.1% to 2.6% (p<0.001), but reduced the magnitude of relative error in bone from -14.6% to 1.3% (p<0.001). The correlation coefficient was essentially unchanged in all tissues regardless of whether bone was included or not. CONCLUSIONS: The approach to include bones in MRI-based attenuation maps described in this work improves quantification of whole-body PET images in and around bony anatomy. The reduction in error is often large (tens of percents), and could alter image interpretation and subsequent patient care. Changes in other parts of the PET image are minimal and likely not of clinical significance.

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 (n = 8) or endocardial injection (n = 13) either on the day of infarction (n = 15) or at 1 week (n = 6). The second injections were administered by only endocardial injection (n = 18) 4 weeks 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 77.1 ± 6.1 (n = 18) versus reperfused 59.4 ± 2.9 h (n = 21) p = 0.009. 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.

Hybrid SPECT/cardiac-gated first-pass perfusion CT: locating transplanted cells relative to infarcted myocardial targets.

PURPOSE: A challenge with cardiac cell therapy is determining the location of cells relative to infarct tissue. As cells are viable following ¹¹¹In-labeling, and first-pass CT imaging can identify regions of myocardial infarction, we evaluated the feasibility of a SPECT/CT system to localize cells relative to infarcted myocardium in a canine model. METHODS: Ten canines underwent surgical ligation of the left-anterior-descending artery and endothelial progenitor cells labeled with ¹¹¹In-tropolone were transplanted endocardially or epicardially. SPECT/CT was performed on day of transplantation, 4 and 10 days post-transplantation. For each imaging session first-pass perfusion CT was performed to delineate the area of reduced perfusion. SPECT and first-pass CT images were fused and evaluated. Contrast-to-noise ratios (CNR) were calculated for ¹¹¹In-SPECT images to evaluate cell detection. RESULTS: The zone of reduced perfusion was well delineated on first-pass perfusion CT in all canines. The ¹¹¹In signal was visualized within this zone in all cases. Analysis of the CNRs suggests that cells may be followed for 11 effective half-lives using the images from first-pass perfusion CT to provide the anatomic landmarks. CONCLUSION: In the setting of an acute myocardial infarction SPECT/[first-pass perfusion CT] is an effective hybrid platform for the localization of cells in relation to the area of reduced blood flow.

Variable lung density consideration in attenuation correction of whole-body PET/MRI.

UNLABELLED: Present attenuation-correction algorithms in whole-body PET/MRI do not consider variations in lung density, either within or between patients; this may adversely affect accurate quantification. In this work, a technique to incorporate patient-specific lung density information into MRI-based attenuation maps is developed and compared with an approach that assumes uniform lung density. METHODS: Five beagles were scanned with (18)F-FDG PET/CT and MRI. The relationship between MRI and CT signal in the lungs was established, allowing the prediction of attenuation coefficients from MRI. MR images were segmented into air, lung, and soft tissue and converted into attenuation maps, some with constant lung density and some with patient-specific lung densities. The resulting PET images were compared by both global metrics of quantitative fidelity (accuracy, precision, and root mean squared error) and locally with relative error in volumes of interest. RESULTS: A linear relationship was established between MRI and CT signal in the lungs. Constant lung density attenuation maps did not perform as well as patient-specific lung density attenuation maps, regardless of what constant density was chosen. In particular, when attenuation maps with patient-specific lung density were used, precision, accuracy, and root mean square error improved in lung tissue. In volumes of interest placed in the lungs, relative error was significantly reduced from a minimum of 12% to less than 5%. The benefit extended to tissues adjacent to the lungs but became less important as distance from the lungs increased. CONCLUSION: A means of using MRI to infer patient-specific attenuation coefficients in the lungs was developed and applied to augment whole-body MRI-based attenuation maps. This technique has been shown to improve the quantitative fidelity of PET images in the lungs and nearby tissues, compared with an approach that assumes uniform lung density.

Quantification of regional myocardial blood flow in a canine model of stunned and infarcted myocardium: comparison of rubidium-82 positron emission tomography with microspheres.

BACKGROUND: Myocardial viability and quantification of regional myocardial blood flow (MBF) are important for the diagnosis of heart disease. Positron emission tomography is the current gold standard for determining myocardial viability, but most positron-emitting perfusion tracers require an on-site cyclotron. Rubidium-82 ((82)Rb) is a myocardial perfusion tracer that is produced using an on-site generator. This study investigates (82)Rb-measured MBF in canine models of stunned and infarcted myocardium compared with selected measurements obtained concurrently using microspheres. METHODS: Myocardial stunning and infarction were created in canines by occluding the left anterior descending for 15 min and 2 h, respectively. Stunning was produced in all animals; six animals were reperfused after the 2 h occlusion, whereas the other six animals remained occluded permanently. Regional MBF was measured in each group during rest and dobutamine stress at acute and chronic (8 weeks postinsult) time points using dynamic (82)Rb perfusion imaging and radioactively labeled microspheres. RESULTS: Average resting MBF with microspheres and Rb was 0.68+/-0.02 versus 0.73+/-0.01 (P<0.001) in nonischemic tissue, and 0.53+/-0.03 versus 0.42+/-0.02 (P<0.001) in the region-at-risk tissue, respectively. Average MBF during stress with microspheres and Rb was 2.78+/-0.15 versus 3.53+/-0.16 (P<0.05) in the nonischemic tissue, and 1.90+/-0.20 versus 2.31+/-0.26 (P = NS) in the region-at-risk tissue, respectively. CONCLUSION: Despite the small significant differences, the dynamic (82)Rb measurements provide estimates of MBF in stunned and acutely and chronically infarcted tissue at rest and during hyperemia that correspond with clinical interpretation.

3D versus 2D dynamic 82Rb myocardial blood flow imaging in a canine model of stunned and infarcted myocardium.

PURPOSE: Previous studies have shown the ability of rubidium-82 ((82)Rb) positron emission tomography (PET) imaging to quantitatively measure myocardial blood flow (MBF), many of which are performed using two-dimensional (2D) imaging. Three-dimensional (3D) imaging provides increased sensitivity and may result in decreased costs owing to a reduction in the required injected activity of radiotracer. This study compares 2D and 3D (82)Rb PET MBF results obtained in the same imaging session. METHODS: Three-dimensional and 2D (82)Rb perfusion imaging was performed in canines on a GE Discovery LS PET/CT scanner at rest and during hyperemia in stunned and infarcted tissue. MBF (ml/min/g) was determined using a 1-compartment model and an extraction correction of the uptake rate and analyzed using a standard 17-segment model. RESULTS: A strong, significant correlation was present (rho = 0.95, P<0.0001). Average 3D MBF values were slightly lower at rest and higher during stress versus 2D. MBF results in normal, stunned, and infarcted tissue differed by 7% on average and significant increases in MBF from rest to hyperemia were noted with both the techniques. CONCLUSION: These results imply that MBF results obtained in 3D are comparable with traditional 2D imaging. Therefore, it may be possible to use 3D imaging with lower administered activity, helping to reduce costs and patient dose without compromising quantitative information.