Eric Sabondjian

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.

SPECT‐based functional lung imaging for the prediction of radiation pneumonitis: A clinical and dosimetric correlation

When we irradiate lung cancer, the radiation dose that can be delivered safely is limited by the risk of radiation pneumonitis (RP) in the surrounding normal lung. This risk is dose‐dependent and is commonly predicted using metrics such as the V20, which are usually formulated assuming homogeneous pulmonary function. Because in vivo pulmonary function is not homogeneous, if highly functioning lung can be identified beforehand and preferentially avoided during treatment, it might be possible to reduce the risk of RP, suggesting the utility of function‐based prediction metrics.

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.

Small field-of-view cardiac SPECT can be implemented on hybrid SPECT/CT platforms where data acquisition and reconstruction are guided by CT.

IntroductionImage truncation in nuclear medicine is a common problem that can lead to artifacts in reconstructed images. We evaluate a modified single-photon emission computed tomography/computed tomography (SPECT/CT) acquisition and reconstruction method for truncated SPECT, which is guided by nontruncated CT. The method nearly eliminates truncation errors, and is ideal for cardiac imaging. We demonstrate its application on phantom and clinical cardiac SPECT/CT scans. Methods99mTc-MIBI (2-methoxy isobutyl isonitrile) SPECT/CT scans were acquired on 14 patients, and on an anthropomorphic cardiac chest phantom. The original 34 × 34 cm field-of-view (FOV) projections were truncated to simulate a small 16 × 16 cm FOV acquisition. Data were reconstructed in three ways: (i) nontruncated and standard reconstruction (NTOSEM), which was our gold standard; (ii) truncated and standard reconstruction (TOSEM); and (iii) truncated and a modified reconstruction (TMOSEM). TMOSEM and TOSEM were both compared with NTOSEM by comparing relative count ratios in the heart, looking at the change in perfusion defect size, and comparing pixel correlation coefficients. ResultsCompared with NTOSEM, the use of TOSEM for small FOV clinical imaging incurred an average count ratio error greater than 100%, and decreased the calculated defect size by 17.13%. For TMOSEM, the average count ratio error was only 8.9%, and the defect size was only decreased by 0.19% compared with NTOSEM. When we plotted TOSEM against NTOSEM a correlation coefficient of 0.734 was calculated, and when we plotted TMOSEM against NTOSEM a correlation coefficient of 0.996 was measured. Comparing NTOSEM with TOSEM in the phantom study produced an average count ratio error greater than 100%. TMOSEM produced an error of 4.3% compared with NTOSEM. ConclusionProjection truncation due to small FOV cameras in cardiac SPECT/CT can lead to significant errors. TMOSEM guided by nontruncated CT reconstruction shows promise in reducing these errors.

Sci—Fri AM: Imaging — 06: The role of body mass and gender in atlas construction for attenuation correction in PET/MRI

Attenuation correction (AC) in PET/MRI is difficult as there is no clear relationship between MR signal and 511 keV attenuation coefficients (μ) as there is with CT. One approach is to register a pre-defined atlas of μ to the PET/MRI for AC. However, the design of the atlas may strongly influence the quantitative accuracy of the AC. Here we compare 3 different atlas design approaches and evaluate their performance in an oncology patient population. The 3 strategies were: use of BMI-dependent atlases; use of gender-dependent atlases, and use of a gender- and sex-independent atlas. Seventeen patients were imaged with FDG PET/CT and subsequently scanned with 3T MRI. MR and PET/CT images were coregistered, CT scans converted to μ-maps, and the resulting MRI/μ-map paired data were used to construct 6 atlases: averaged male and female atlases, averaged BMI-specific atlases (obese >30, overweight 25-29.9, Normal 18.5-24.9), and a single atlas comprised of all patients averaged together. The atlases were then used for PET AC for patients not included in the construction of the atlas in a leave-one-out manner. Resulting PET images were compared to each other and to the gold-standard CT-based PET reconstructions across all voxels and tissue-specific regions (soft-tissue, bone, lung). Sex-specific atlases yielded best results (average relative percent error over the 3 VOIs = 0.4509) & BMI-based atlases yielded highest average relative percent error at 0.9340. In all cases, highest errors were in the VOIs located in the livers.

SU‐E‐I‐154: Cardiac SPECT/CT: Comparing Slow‐Rotation and Fast‐Rotation CT for Attenuation Correction in Cardiac Imaging

Purpose: The hybridisation of SPECT with X‐ray CT is expanding the utility of SPECT. In addition to image fusion, CT enables improved attenuation maps (AM) for SPECT. Two CT designs are used in SPECT/CT: slow‐ rotation and fast‐rotation. The “slow‐rotation” CT completes a full‐rotation in 15 seconds to provide an AM that is acquired over several frames of the respiratory cycle; hence includes motion related physiologic artifacts. The “fast‐rotation” CT completes a full‐rotation in 0.6 seconds to provide an AM that is comparatively free of breathing artifacts. Neither is similar to SPECT, which is acquired in a step‐and‐shoot manner, where each projection is acquired over all frames of the respiratory cycle. Methods: We compared cardiac SPECT/CT acquisitions with the General Electric Infinia/Hawkeye‐4 which incorporates a slow‐rotating CT and the Siemens Symbia/T6 which incorporates a fast‐rotating CT. Three canine experiments were performed comparing SPECT reconstructions that were corrected for attenuation with no respiratory motion between SPECT and CT (gold standard). These were compared with SPECT reconstructions that incorporated respiratory motion and corrected for attenuation using either the slow or fast‐CT AMs. The SPECT reconstructions were compared using a Root‐Mean‐Squared (RMS) metric and scatter plots, calculated pixel‐by‐ pixel in a region‐of‐interest through a central slice of the heart. Results: The canine experiments showed improvements in both the RMS error and correlation coefficients for all canines when using the fast‐CT AM. The average RMS error improved from 28% to 17%, while the average correlation coefficient improved from 0.85 to 0.96. Canine studies confirmed respiratory motion has the potential to corrupt CT data and can effect attenuation correction in SPECT. Conclusions: Artifacts in the attenuation map due to physiologic motion propagate into the SPECTimage reconstructions causing erroneous results. Therefore, for SPECT to become more quantitative an attenuation map with fewer artifacts is desirable.

Sci—Fri AM: Imaging — 09: Hybrid SPECT and First‐Pass Perfusion CT: Application in Cell Localization

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 CTimaging can identify regions of myocardial infarction, we evaluated the feasibility of a SPECT/CT system to localize and track cells relative to infarcted myocardium in a canine model. Methods: To determine accuracy of SPECT/CT registration, images were acquired of capillary tubes filled with CT and SPECT contrast agents. Accuracy was measured by comparing locations of tube centroids in SPECT and CT. 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 infarct zone. SPECT and first‐pass CTimages were fused and evaluated. Delayed‐enhanced MRI was performed to validate CT infarct localization. Contrast‐to‐noise ratios (CNR) were calculated for 111In‐SPECT images to evaluate cell detection. Results: Phantom SPECT/CT registration accuracy was approximately 1mm. The infarct zone was well delineated on first‐pass perfusion CT in all canines and correlated well with MRI findings. 111In signal was visualized within the infarct zone in all cases. Analysis of the CNRs suggests that cells can be followed for 11 effective half‐lives provided the location of the cells can be inferred by first‐pass CT.Conclusion: SPECT/[First‐Pass Perfusion CT] is an effective hybrid platform for the localization and tracking of stem cells in relation to infarct tissue.

Sci-Thurs AM: YIS-11: A Hybrid SPECT and Contrast Enhanced CT Platform: Application in Stem Cell Therapy

Cell therapy in treating acute myocardial infarction is currently being investigated. A challenge associated with stem cell therapy is localization of the cells with reference to the region of infarct. As stem cells have been shown to remain viable after 111 In labeling, with hybrid SPECT/CT systems incorporating diagnostic quality CTs, it may be feasible to fuseSPECTimages of the cells with contrast enhanced CTimages. With the ability to perform contrast enhanced CT, this will allow anatomic localization and tracking of transplanted cells in relationship to the area of infarct. Accuracy of our SPECT/CT system (Siemens, Symbia T‐6) was established with capillary tubes filled with a CTcontrast agent and 99 m Tc that were arranged to evaluate registration in all three dimensions. Tube centroid locations in SPECT and CTreconstructed images were used for accuracy measurements, which were shown to be close to 1mm. Subsequently, three adult canines underwent a surgical ligation of the left anterior descending artery. Endothelial progenitor cells were labeled with 111 In and injected using a left ventricular catheter one‐week post surgery. SPECT/CT was performed on injection day. For the imaging session, a bolus of CTcontrast agent was administered and a gated CT was performed immediately after the bolus injection. SPECT and contrast enhanced CTimages were then fused on the SPECT/CT. For all canine imaging sessions, the infarct boundary was delineated clearly on contrast enhanced CT, and the center of the 111 In focus was located within the infarct boundary.