Improvements in Cardiac Spect/CT for the Purpose of Tracking Transplanted Cells

Regenerative therapy via stem cell transplantation has received increased attention to help treat the myocardial injury associated with heart disease. Currently, the hybridisation of SPECT with X-ray CT is expanding the utility of SPECT. This thesis compared two SPECT/CT systems for attenuation correction using slow or fast-CT attenuation maps (mu-maps). We then developed a method to localize transplanted cells in relation to compromised blood flow in the myocardium following a myocardial infarction using SPECT/CT. Finally, a method to correct for image truncation was studied for a new SPECT/CT design that incorporated small field-of-view (FOV) detectors. Computer simulations compared gated-SPECT reconstructions using slow-CT and fast-CT mu-maps with gated-CT mu-maps. Using fast-CT mu-maps improved the Root Mean Squared (RMS) error from 4.2% to 4.0%. Three canine experiments were performed comparing SPECT/CT reconstruction using the Infinia/Hawkeye-4 (slow-CT) and Symbia T6 (fast-CT). Canines were euthanized prior to imaging, and then ventilated. The results showed improvements in both RMS errors and correlation coefficients for all canines. A first-pass contrast CT imaging technique can identify regions of myocardial infarction and can be fused with SPECT. Ten canines underwent surgical ligation of the left-anterior-descending artery. Cells were labeled with 111In-tropolone and transplanted into the myocardium. SPECT/CT was performed on day of transplantation, 4, and 10 days post-transplantation. For each imaging session first-pass perfusion CT was performed and successfully delineated the infarct zone. Delayed-enhanced MRI was performed and correlated well with first-pass CT. Contrast-to-noise ratios were calculated for 111In-SPECT and suggested that cells can be followed for 11 effective half-lives. We evaluated a modified SPECT/CT acquisition and reconstruction method for truncated SPECT. Cardiac SPECT/CT scans were acquired in 14 patients. The original projections were truncated to simulate a small FOV acquisition. Data was reconstructed in three ways: non-truncated and standard reconstruction (NTOSEM), which was our gold-standard; truncated and standard reconstruction (TOSEM); and truncated and a modified reconstruction (TMOSEM). Compared with NTOSEM, small FOV imaging incurred an average cardiac count ratio error greater than 100% using TOSEM and 8.9% using TMOSEM. When we plotted NTOSEM against TOSEM and TMOSEM the correlation coefficient was 0.734 and 0.996 respectively

Comparison of initial cell retention and clearance kinetics after subendocardial or subepicardial injections of endothelial progenitor cells in a canine myocardial infarction model

Neither intravenous nor intracoronary routes provide targeted stem cell delivery to recently infarcted myocardium in sufficient quantities. Direct routes appear preferable. However, most prior studies have used epicardial injections, which are not practical for routine clinical use. The objective of this study was to compare cell retention and clearance kinetics between a subepicardial and a subendocardial technique. Methods: We evaluated 7 dogs with each technique, using 111In-tropolone-labeled endothelial progenitor cells and serial SPECT/CT for 15 d after injection. Results: In vivo indium imaging demonstrated comparable degrees of retention: 57% ± 15% for the subepicardial injections and 54% ± 26% for the subendocardial injections. Clearance half-lives were also similar at 69 ± 26 and 60 ± 21 h, respectively. Conclusion: This study demonstrates that subendocardial injections, clinically more practical, show clearance kinetics comparable to those of subepicardial injections and will facilitate the ultimate clinical use of this treatment modality. Copyright © 2010 by the Society of Nuclear Medicine, Inc

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. © 2012 The Author(s)

In Vivo Dosimetry for Superficial High Dose Rate Brachytherapy with Optically Stimulated Luminescence Dosimeters: A Comparison Study with Metal-Oxide-Semiconductor Field-Effect Transistors

The purpose of the study was to calibrate and commission optically-stimulated luminescence dosimeters (OSLDs) for in vivo measurements in contact-based 192Ir treatments for superficial high dose rate (HDR) brachytherapy in place of metal-oxide-semiconductor field-effect transistors (MOSFETs). Dose linearity and dose rate dependence were tested by varying source-to-OSLD distance and dwell time. Angular dependence was measured using a solid water phantom setup for OSLD rotation. A group of OSLDs were readout 34 consecutive times to test readout depletion while OSLDs were optically annealed using a mercury lamp for 34.7 h. End-to-end tests were performed using a Freiburg flap and Valencia applicator. OSLD measurements were compared to MOSFETs and treatment planning system (TPS) doses. OSLD response was supralinear for doses above 275 cGy. They were found to be independent of dose rate and dependent on the incident angle in edge-on scenarios. OSLDs exhibited minimal readout depletion and were successfully annealed after 24 h of illumination. Freiburg flap measurements agreed well with the TPS. For the Valencia, OSLDs showed to be the more accurate system over MOSFETs, with a maximum disagreement with the TPS being 0.09%. As such, OSLDs can successfully be used in place of MOSFETs for in vivo dosimetry for superficial HDR brachytherapy

In Vivo Dosimetry for Superficial High Dose Rate Brachytherapy with Optically Stimulated Luminescence Dosimeters: A Comparison Study with Metal-Oxide-Semiconductor Field-Effect Transistors

The purpose of the study was to calibrate and commission optically-stimulated luminescence dosimeters (OSLDs) for in vivo measurements in contact-based 192Ir treatments for superficial high dose rate (HDR) brachytherapy in place of metal-oxide-semiconductor field-effect transistors (MOSFETs). Dose linearity and dose rate dependence were tested by varying source-to-OSLD distance and dwell time. Angular dependence was measured using a solid water phantom setup for OSLD rotation. A group of OSLDs were readout 34 consecutive times to test readout depletion while OSLDs were optically annealed using a mercury lamp for 34.7 h. End-to-end tests were performed using a Freiburg flap and Valencia applicator. OSLD measurements were compared to MOSFETs and treatment planning system (TPS) doses. OSLD response was supralinear for doses above 275 cGy. They were found to be independent of dose rate and dependent on the incident angle in edge-on scenarios. OSLDs exhibited minimal readout depletion and were successfully annealed after 24 h of illumination. Freiburg flap measurements agreed well with the TPS. For the Valencia, OSLDs showed to be the more accurate system over MOSFETs, with a maximum disagreement with the TPS being 0.09%. As such, OSLDs can successfully be used in place of MOSFETs for in vivo dosimetry for superficial HDR brachytherapy