Assessing the impact of radiation-induced changes in soft tissue density ∕ thickness on the study of radiation-induced perfusion changes in the lung and heart.

PURPOSE: Abnormalities in single photon emission computed tomography (SPECT) perfusion within the lung and heart are often detected following radiation for tumors in∕around the thorax (e.g., lung cancer or left-sided breast cancer). The presence of SPECT perfusion defects is determined by comparing pre- and post-RT SPECT images. However, RT may increase the density of the soft tissue surrounding the lung∕heart (e.g., chest wall∕breast) that could possibly lead to an "apparent" SPECT perfusion defect due to increased attenuation of emitted photons. Further, increases in tissue effective depth will also increase SPECT photon attenuation and may lead to "apparent" SPECT perfusion defects. The authors herein quantitatively assess the degree of density changes and effective depth in soft tissues following radiation in a series of patients on a prospective clinical study. METHODS: Patients receiving thoracic RT were enrolled on a prospective clinical study including pre- and post-RT thoracic computed tomography (CT) scans. Using image registration, changes in tissue density and effective depth within the soft tissues were quantified (as absolute change in average CT Hounsfield units, HU, or tissue thickness, cm). Changes in HU and tissue effective depth were considered as a continuous variable. The potential impact of these tissue changes on SPECT images was estimated using simulation data from a female SPECT thorax phantom with varying tissue densities. RESULTS: Pre- and serial post-RT CT images were quantitatively studied in 23 patients (4 breast cancer, 19 lung cancer). Data were generated from soft tissue regions receiving doses of 20-50 Gy. The average increase in density of the chest was 5 HU (range 46 to -69). The average change in breast density was a decrease of -1 HU (range 13 to -13). There was no apparent dose response in neither the dichotomous nor the continuous analysis. Seventy seven soft tissue contours were created for 19 lung cancer patients. The average change in tissue effective depth was +0.2 cm (range -1.9 to 2.2 cm). The changes in HU represent a <2% average change in tissue density. Based on simulation, the small degree of density and tissue effective depth change is unlikely to yield meaningful changes in either SPECT lung or heart perfusion. CONCLUSIONS: RT doses of 20-50 Gy can cause up to a 46 HU increase in soft tissue density 6 months post-RT. Post-RT soft tissue effective depth may increase by 2.0 cm. These modest increases in soft tissue density and effective depth are unlikely to be responsible for the perfusion changes seen on post-RT SPECT lung or heart scans. Further, there was no clear dose response of the soft tissue density changes. Ultimately, the authors findings suggest that prior perfusion reports do reflect changes in the physiology of the lungs and heart.

Slit-Slat and Multislit-Slat Collimator Design and Experimentally Acquired Phantom Images from a Rotating Prototype.

We have previously found and validated expressions for slit-slat (SS) geometric efficiency and resolution. These expressions have suggested that SS may be a good choice for imaging mid-size objects or objects that are long axially since (i) the geometric efficiency increases near the slit as h(-1) (instead of h(-2) for pinhole (PIN) and either decreases near the collimator for fan-beam (FB) or remains constant for parallel-beam (PB)), where h is the distance from a point to the slit plane; (ii) the transverse resolution is comparable to that of PIN, which is better than that of FB and PB for small objects; (iii) the axial resolution is worse than that of PIN since there is no axial magnification; (iv) there is a large axial FOV, unlike PIN, which is likely to be useful when imaging mid-size or long objects; and (v) there is no need for 3D orbits (e.g., helical) since each slice is complete (like PB and FB).We have developed a rotating prototype SS collimator that is capable of single-slit or multi-slit acquisition of data. The focal length (FL) is shorter than that of a typical PIN since increasing the FL requires taller slats to maintain resolution; taller slats reduce geometric efficiency. A lead rectangular box was used to provide support and shielding around the slit-slat collimator. Lead slats, spaced with Rohacell foam, were mounted in an assembly with 3 mm pitch.We have performed preliminary characterization with point sources and acquired micro hot- and cold-rod phantoms and a Deluxe Jaszczak phantom. The projections have been reconstructed using an MLEM algorithm and show good resolution.Comparisons indicate that SS is more sensitive than PB and FB for the same resolution for smaller-diameter objects. The advantage of SS over PB and FB increases as the desired resolution improves. SS can also be used in configurations that yield projections that have non-isotropic resolution; it is possible for SS to achieve transverse resolutions that are unreachable by PB, since PB does not magnify, and by FB, since its magnification factor for small objects is much smaller than that of SS. Experimental results show that the resolution of the reconstructed phantoms is consistent with theoretical expectations.

Feasibility of whole-body functional mouse imaging using helical pinhole SPECT.

PURPOSE: Detailed in vivo whole-body biodistributions of radiolabeled tracers may characterize the longitudinal progression of disease, and changes with therapeutic interventions. Small-animal imaging in mice is particularly attractive due to the wide array of well characterized genetically and surgically created models of disease. Single Photon Emission Computed Tomography (SPECT) imaging using pinhole collimation provides high resolution and sensitivity, but conventional methods using circular acquisitions result in severe image truncation and incomplete sampling of data, which prevent the accurate determination of whole-body radiotracer biodistributions. This study describes the feasibility of helical acquisition paths to mitigate these effects. PROCEDURES: Helical paths of pinhole apertures were implemented using an external robotic stage aligned with the axis of rotation (AOR) of the scanner. Phantom and mouse scans were performed using helical paths and either circular or bi-circular orbits at the same radius of rotation (ROR). The bi-circular orbits consisted of two 360-degree scans separated by an axial shift to increase the axial field of view (FOV) and to improve the complete-sampling properties. RESULTS: Reconstructions of phantoms and mice acquired with helical paths show good image quality and are visually free of both truncation and axial-blurring artifacts. Circular orbits yielded reconstructions with both artifacts and a limited effective FOV. The bi-circular scans enlarged the axial FOV, but still suffered from truncation and sampling artifacts. CONCLUSIONS: Helical paths can provide complete sampling data and large effective FOV, yielding 3D full-body in vivo biodistributions while still maintaining a small distance from the aperture to the object for good sensitivity and resolution.

Radiation-induced reductions in regional lung perfusion: 0.1-12 year data from a prospective clinical study.

PURPOSE: To assess the time and regional dependence of radiation therapy (RT)-induced reductions in regional lung perfusion 0.1-12 years post-RT, as measured by single photon emission computed tomography (SPECT) lung perfusion. MATERIALS/METHODS: Between 1991 and 2005, 123 evaluable patients receiving RT for tumors in/around the thorax underwent SPECT lung perfusion scans before and serially post-RT (0.1-12 years). Registration of pre- and post-RT SPECT images with the treatment planning computed tomography, and hence the three-dimensional RT dose distribution, allowed changes in regional SPECT-defined perfusion to be related to regional RT dose. Post-RT follow-up scans were evaluated at multiple time points to determine the time course of RT-induced regional perfusion changes. Population dose response curves (DRC) for all patients at different time points, different regions, and subvolumes (e.g., whole lungs, cranial/caudal, ipsilateral/contralateral) were generated by combining data from multiple patients at similar follow-up times. Each DRC was fit to a linear model, and differences statistically analyzed. RESULTS: In the overall groups, dose-dependent reductions in perfusion were seen at each time post-RT. The slope of the DRC increased over time up to 18 months post-RT, and plateaued thereafter. Regional differences in DRCs were only observed between the ipsilateral and contralateral lungs, and appeared due to tumor-associated changes in regional perfusion. CONCLUSIONS: Thoracic RT causes dose-dependent reductions in regional lung perfusion that progress up to approximately 18 months post-RT and persists thereafter. Tumor shrinkage appears to confound the observed dose-response relations. There appears to be similar dose response for healthy parts of the lungs at different locations.

Combination of converging collimators for high-sensitivity brain SPECT.

UNLABELLED: The objective of this study, which is related to human brain SPECT, was to increase the sensitivity of a triple-camera SPECT system and reduce statistical noise in reconstructed images using a combination of converging collimators. The reason for combining collimators is to ensure both high sensitivity and sufficient sampling without trading off spatial resolution. METHODS: A high-sensitivity half-cone-beam (HCB) collimator, designed specifically for brain imaging, was combined with other collimators and compared with conventional parallel-beam and fanbeam circular orbit acquisitions. For comparison, previously studied HCB collimation with a circle-and-helix data acquisition trajectory was also included in this study. Simulations of the Hoffman 3-dimensional brain phantom were performed to calculate the efficiencies of collimators and their combinations and to quantitatively evaluate reconstruction bias, statistical noise, and signal-to-noise ratios in the reconstructed images. Experimental brain phantom data were also acquired and compared for different acquisition types. Finally, a patient brain scan was obtained with a combination of HCB and fanbeam collimators and compared with a triple-fanbeam circular orbit acquisition. RESULTS: A combination of 2 HCB collimators and 1 fanbeam collimator, compared with a triple-fanbeam collimator, can increase the photon detection efficiency by 27% and by more than a factor of 2, compared with triple-parallel-hole collimation, with equal spatial resolution measured on the axis of rotation. Quantitative analysis of reconstruction bias and visual analysis of the images showed no signs of sampling artifacts. Reconstructed images in the simulations, experimental brain phantom, and patient brain scans showed improved quality with this collimator combination due to increased sensitivity and reduced noise. Lesion visibility was also improved, as confirmed by signal-to-noise ratios. Alternatively, triple-HCB circle-and-helix acquisition has also shown competitive results, with a slight disadvantage in axial sampling and implementation procedure. CONCLUSION: Combined HCB and fanbeam collimation is a promising approach for high-sensitivity brain SPECT.

Quantitative Evaluation of Half-Cone-Beam Scan Paths in Triple-Camera Brain SPECT.

In this study related to human brain SPECT imaging, simulation of half-cone-beam (HCB) collimation with different scan paths is performed and compared with simulated fan-beam and parallel-hole circular orbit acquisitions of disk-phantom projection data. Acquisition types are quantitatively evaluated based on the photon detection efficiency, the root-mean-squared error, contrast and signal-to-noise ratio measurements of the reconstructed images. We demonstrate that a triple-camera SPECT system with half-cone-beam collimators and circle-and-helix scan paths can offer up to a 26% efficiency increase over fan-beam, and up to a 128% increase over parallel-hole collimators for equal spatial resolutions, and display no visible axial sampling artifacts in reconstructed disk-phantom images. In addition, we perform qualitative experimental evaluation of triple-HCB circle-and-helix acquisition using a Hoffman 3D brain phantom. Reconstructed brain phantom images show improved quality due to reduced noise and no apparent sampling artifacts. Triple-HCB circle-and-helix SPECT has a potential for improved brain imaging, producing higher image quality with a smaller reconstruction error and better lesion detectability due to increased efficiency for equal spatial resolution compared to conventional fan-beam and parallel-hole SPECT.

Left ventricular functional assessment in mice: feasibility of high spatial and temporal resolution ECG-gated blood pool SPECT.

PURPOSE: To prospectively determine feasibility of evaluating murine left ventricular (LV) function with electrocardiographically (ECG)-gated blood pool single photon emission computed tomography (SPECT). MATERIALS AND METHODS: All animal studies had institutional animal care and use committee approval. SPECT was performed with conventional time-binned acquisition (eight frames per ECG cycle) in normal mice (normal group A, n = 6) and mice with myocardial infarction (MI) (n = 8). To determine feasibility of high temporal resolution and rapid data acquisition, another group of normal mice (normal group B, n = 4) underwent imaging with conventional (eight-frame) time-binned and list-mode (LM) acquisitions. LM acquisitions were reconstructed with eight and 16 frames per ECG cycle and 10 minutes of data (short LM). SPECT images were assessed visually, and LV-to-lung background activity ratios were calculated. LV end-systolic and end-diastolic volumes were defined with a phase analysis and threshold method. LV ejection fraction (LVEF) was calculated from LV volumes and count-based methods (n = 18 mice). Fractional shortening (FS) at echocardiography defined MI dysfunction (mild MI: FS > or = 50%; severe MI: FS < 50%). Group means were compared for significant differences with analysis of variance. RESULTS: ECG-gated blood pool SPECT demonstrated normal, concentric LV contraction in all normal mice (n = 10). LV-to-lung background ratio was more than 10:1 (range, 10.3-29.4; n = 18). Focal wall motion abnormalities were detected at SPECT both visually and with phase analysis in all mice with severe MI (n = 5). Mice with severe MI had significantly lower LVEF than normal group A mice (32% +/- 14 [standard deviation] vs 64% +/- 8%; P < .001). All mice with mild MI (n = 3) had normal contraction and LVEF. In paired acquisitions in normal group B mice, all reconstructions (n = 16) showed normal LV contraction. LVEF was not significantly different (P = .88) between time-binned (71% +/- 12), eight-frame LM (71% +/- 12), 16-frame LM (77% +/- 10), and short LM (73% +/- 14) reconstructions. CONCLUSION: Murine LV functional assessment is feasible with high spatial and temporal resolution ECG-gated blood pool SPECT. LV dysfunction can be quantified and focal wall motion abnormalities detected in the MI model of heart failure.

Cell therapy in murine atherosclerosis: in vivo imaging with high-resolution helical SPECT.

PURPOSE: To determine the feasibility of in vivo localization and quantification of indium 111 (111In)-oxine-labeled bone marrow (BM) with high-resolution whole-body helical single photon emission computed tomography (SPECT) in an established murine model of atherosclerosis and vascular repair. MATERIALS AND METHODS: The institutional animal care and use committee approved this study. BM from young B6 Rosa 26 Lac Z+/+ mice was radiolabeled with 111In-oxine. On days 1, 4, and 7 after administration of radiolabeled cells, five C57/BL6 apolipoprotein E-deficient mice and five wild-type (WT) control mice were imaged with whole-body high-resolution helical SPECT. Quantification with SPECT was compared with ex vivo analysis by means of gamma counting. Autoradiography and beta-galactosidase staining were used to verify donor cell biodistribution. Linear regression was used to assess the correlation between continuous variables. Two-tailed Student t test was used to compare values between groups, and paired two-tailed t test was used to assess changes within subjects at different time points. RESULTS: SPECT image contrast was high, with clear visualization of BM, liver, and spleen 7 days after administration of radiolabeled cells. SPECT revealed that 42% and 58% more activity was localized to the aorta and BM (P<.05 for both), respectively, in apolipoprotein E-deficient mice versus WT mice. Furthermore, 28% and 27% less activity was localized to the liver and spleen (P<.05 for both), respectively, in apolipoprotein E-deficient mice versus WT mice. SPECT and organ gamma counts showed good quantitative correlation (r=0.9). beta-Galactosidase staining and microautoradiography of recipient aortas showed donor cell localization to the intima of visible atherosclerotic plaque but not to unaffected regions of the vessel wall. CONCLUSION: High-resolution in vivo helical pinhole SPECT can be used to monitor and quantify early biodistribution of 111In-oxine-labeled BM in a murine model of progenitor cell therapy for atherosclerosis.

Brain SPECT Simulation Using Half-Cone-Beam Collimation and Single-Revolution Helical-Path Acquisition.

In this study related to human brain SPECT imaging, simulation of half-cone-beam collimation and helical-path data acquisition is performed. We discuss problems related to circular-orbit acquisition using cone-beam collimation, such as shoulder interference resulting in object truncation, and insufficient sampling of the object resulting in axial distortions in the reconstructed images. We demonstrate that a triple-camera SPECT system with half-cone-beam collimation and single-revolution helical-path acquisition eliminates both issues and offers substantially improved sampling and almost artifact-free reconstruction of the object.

On-axis sensitivity and resolution of a slit-slat collimator.

UNLABELLED: A slit-slat collimator combines a slit along the axis of rotation with a set of axial septa, offering both magnification in the transaxial direction and complete sampling with just a circular orbit. This collimator has a sensitivity that increases for points near the aperture slit. The literature treats this collimator as having the same sensitivity as a single-pinhole collimator, ignoring the effect of the axial septa. Herein, the sensitivity and resolution of this collimator are reevaluated. METHODS: Experimental and Monte Carlo methods are used to determine the sensitivity and resolution in both the transaxial and axial directions as a function of distance from the slit (h). Eight configurations are tested, varying the slit width, septal spacing, and septal height. RESULTS: Both the experimental and the Monte Carlo sensitivities agree reasonably with an analytic form that is the geometric mean of the pinhole and parallel-beam formulas, disagreeing with previous literature. Transaxial resolution is consistent with the pinhole-resolution formula. Axial resolution is consistent with the parallel-beam resolution formula. CONCLUSION: The sensitivity of this collimator is proportional to h(-1) and has resolution in the transaxial direction that is consistent with pinhole resolution and in the axial direction that is consistent with parallel-beam resolution.

Mammotomography with pinhole incomplete circular orbit SPECT.

UNLABELLED: Dedicated mammotomography with pinhole incomplete circular orbit (PICO) SPECT imaging of an uncompressed pendant breast was evaluated with small, very-high-stopping-power pinhole apertures. Comparisons were made with planar pinhole scintimammography. Enhanced 3-dimensional imaging performance with very-high-stopping-power apertures is thought to ultimately yield improved sensitivities for lesion detection and identification in breast disease. METHODS: Pinhole collimators made of high-density and high atomic number (184)W or depleted (238)U, with aperture diameters from 1 to 4 mm, were used to image 0.6- and 1.0-cm-diameter spherical lesions in a pendulous, uncompressed breast phantom in planar and PICO-SPECT modes. The breast was centered on the horizontal axis of rotation of an incomplete circular orbit. Lesion, breast and body, and myocardial activities (L:B:M) were included in the phantoms to simulate clinical imaging conditions with (99m)Tc (140 keV). Lesion contrasts and signal-to-noise ratios (SNRs) for all apertures were determined for near clinical acquisition times for L:B:M ratios of 12:1:20 and 7:1:25. A set of minidisks inserted in the breast phantom was scanned to determine sampling limitations at depth from the nipple. In an initial study, a patient with biopsy-confirmed breast carcinoma was injected with 960 MBq (99m)Tc-tetrofosmin and scanned 2 h later with planar pinhole and PICO-SPECT techniques. RESULTS: Overall, for PICO-SPECT imaging there were small differences in measured counting rate sensitivity (4.9%) and lesion contrast (8.8%) with larger SNR differences (20.8%) between tungsten and depleted uranium pinhole materials at this energy and these lesion sizes. Backgrounds from simulated myocardial uptake had minor contributions in all reconstructed image volumes because of the rapid sensitivity fall-off for pinhole apertures. An optimal aperture diameter between 2 and 3 mm was determined from peak SNR, indicating that these aperture sizes may have the best performance for lesions as small as 0.6 cm in diameter with activity concentration ratios of (99m)Tc similar to those currently seen in patients. Both lesions were visualized with PICO-SPECT better than with planar pinhole imaging, with respective contrast improvements >20 times the values obtained from planar imaging for the same pinholes. In the patient study, higher contrast (>6) visualization of the active tumor periphery was obtained with PICO-SPECT than with planar imaging. CONCLUSION: These results indicate that the enhanced spatial resolution of smaller apertures outweighs the loss in sensitivity in small lesion identification with PICO-SPECT. Although the imaging differences between investigated aperture types are small and some limitations to this imaging approach exist, dedicated PICO-SPECT of the breast appears to be an improved technique compared with conventional planar pinhole scintimammography. This technique provides enhanced contrast and SNR for imaging small lesions with the high-resolution pinhole apertures along with 3-dimensional localization of the lesions.

Receiver operating characteristic curves to assess predictors of radiation-induced symptomatic lung injury.

PURPOSE: To assess the utility of dosimetric/functional metrics as predictors of symptomatic radiation pneumonitis using receiver operating characteristic curves. METHODS: Between 1991 and 1999, 277 patients were enrolled on a prospective clinical study to relate radiation therapy (RT) induced changes in lung function with dosimetric and functional metrics. Pre-RT whole and regional functional assessments included pulmonary function tests and single photon emission computed tomography lung perfusion scans. Patients had three-dimensional planning scans and dose calculations (reflecting tissue density heterogeneity) to provide a dose-volume histogram of the lung and associated dosimetric parameters (MLD = mean lung dose, V30 = % of lung receiving >or=30 Gy). Fusion of single photon emission computed tomography and computed tomography scans provides perfusion-weighted dose-function histograms and associated dosimetric parameters (mean perfusion-weighted lung dose). The incidence of clinically relevant radiation pneumonitis requiring steroids was related to the dosimetric and functional metrics. The predictive abilities of models (sensitivity and specificity) were calculated and compared based on the area beneath receiver operating characteristic (ROC) curves (Wilcoxon rank-sum and chi-square). RESULTS: Twenty-seven of 162 evaluable patients with >or=6 months' follow-up developed pneumonitis requiring steroids. Single metrics were typically not good predictors for pneumonitis ( area under ROC curve = 0.5-0.68). The two-dimensional models (e.g., MLD and pre-RT diffusion capacity for carbon monoxide) generally provided greater ROC areas (0.61-0.72). Overall, the models that considered a measure of pre-RT lung function (i.e., pulmonary function tests), the MLD, and mean perfusion-weighted lung dose were best correlated with outcome (ROC area: 0.7) (p < 0.05 compared to unidimensional models). However, because the area under the ROC curve for these models was <<1, they too seemed not to be ideal. CONCLUSION: Predicting symptomatic radiation pneumonitis remains difficult. Multiparameter models that consider pre-RT pulmonary function and the three-dimensional dose distribution seem to be best able to predict outcome. Additional studies are needed to better understand the dosimetric/functional determinants of radiation pneumonitis.

The time course of radiation therapy-induced reductions in regional perfusion: a prospective study with >5 years of follow-up.

PURPOSE: To assess the time-dependence of radiation therapy (RT)-induced reductions in regional lung perfusion, as measured by single photon emission computed tomography (SPECT) lung perfusion scans. METHODS AND MATERIALS: Between 1991 and 1999, 79 patients had SPECT lung perfusion scans before and serially after RT. Changes in regional perfusion were correlated with regional dose using 3D planning tools and image fusion (PLUNC-Plan UNC). Multiple post-RT follow-up scans were evaluated to determine the temporal nature of RT-induced regional perfusion changes. To facilitate the comparison of dose-response curves (DRCs) at different post-RT intervals, each DRC was fit to a linear model and thus described by its slope. RESULTS: There was a dose-dependent reduction in regional perfusion at nearly all time points post-RT (p = 0.0001). The slope of the DRCs for RT-induced reductions in regional perfusion became steeper at essentially each successive follow-up interval (p = 0.0001). However, the increases in slope became progressively smaller at later follow-up intervals. Overall, about 80% of the long-term RT-induced regional perfusion injury was manifest within 12 months post-RT. CONCLUSION: There is a progression of RT-induced reductions in regional perfusion, with most of this injury manifest within 12 months post-RT. Additional regional injury appears to evolve for years.