Demonstration of real-time positron emission tomography biology-guided radiotherapy delivery to targets.

BACKGROUND: Biology-guided radiotherapy (BgRT) is a novel technology that uses positron emission tomography (PET) data to direct radiotherapy delivery in real-time. BgRT enables the precise delivery of radiation doses based on the PET signals emanating from PET-avid tumors on the fly. In this way, BgRT uniquely utilizes radiotracer uptake as a biological beacon for controlling and adjusting dose delivery in real-time to account for target motion. PURPOSE: To demonstrate using real-time PET for BgRT delivery on the RefleXion X1 radiotherapy machine. The X1 radiotherapy machine is a rotating ring-gantry radiotherapy system that generates a nominal 6MV photon beam, PET, and computed tomography (CT) components. The system utilizes emitted photons from PET-avid targets to deliver effective radiation beamlets or pulses to the tumor in real-time. METHODS: This study demonstrated a real-time PET BgRT delivery experiment under three scenarios. These scenarios included BgRT delivering to (S1 ) a static target in a homogeneous and heterogeneous environment, (S2 ) a static target with a hot avoidance structure and partial PET-avid target, and (S3 ) a moving target. The first step was to create stereotactic body radiotherapy (SBRT) and BgRT plans (offline PET data supported) using RefleXion's custom-built treatment planning system (TPS). Additionally, to create a BgRT plan using PET-guided delivery, the targets were filled with 18F-Fluorodeoxyglucose (FDG), which represents a tumor/target, that is, PET-avid. The background materials were created in the insert with homogeneous water medium (for S1 ) and heterogeneous water with styrofoam mesh medium. A heterogeneous background medium simulated soft tissue surrounding the tumor. The treatment plan was then delivered to the experimental setups using a pre-commercial version of the X1 machine. As a final step, the dosimetric accuracy for S1 and S2 was assessed using the ArcCheck analysis tool-the gamma criteria of 3%/3 mm. For S3 , the delivery dose was quantified using EBT-XD radiochromic film. The accuracy criteria were based on coverage, where 100% of the clinical target volume (CTV) receives at least 97% of the prescription dose, and the maximum dose in the CTV was ≤130% of the maximum planned dose (97 % ≤ CTV ≤ 130%). RESULTS: For the S1, both SBRT and BgRT deliveries had gamma pass rates greater than 95% (SBRT range: 96.9%-100%, BgRT range: 95.2%-98.9%), while in S2 , the gamma pass rate was 98% for SBRT and between 95.2% and 98.9% for BgRT plan delivering. For S3 , both SBRT and BgRT motion deliveries met CTV dose coverage requirements, with BgRT plans delivering a very high dose to the target. The CTV dose ranges were (a) SBRT:100.4%-120.4%, and (b) BgRT: 121.3%-139.9%. CONCLUSIONS: This phantom-based study demonstrated that PET signals from PET-avid tumors can be utilized to direct real-time dose delivery to the tumor accurately, which is comparable to the dosimetric accuracy of SBRT. Furthermore, BgRT delivered a PET-signal controlled dose to the moving target, equivalent to the dose distribution to the static target. A future study will compare the performance of BgRT with conventional image-guided radiotherapy.

BIOGUIDE-X: A First-in-Human Study of the Performance of Positron Emission Tomography-Guided Radiation Therapy.

PURPOSE: Positron emission tomography (PET)-guided radiation therapy is a novel tracked dose delivery modality that uses real-time PET to guide radiation therapy beamlets. The BIOGUIDE-X study was performed with sequential cohorts of participants to (1) identify the fluorodeoxyglucose (FDG) dose for PET-guided therapy and (2) confirm that the emulated dose distribution was consistent with a physician-approved radiation therapy plan. METHODS AND MATERIALS: This prospective study included participants with at least 1 FDG-avid targetable primary or metastatic tumor (2-5 cm) in the lung or bone. For cohort I, a modified 3 + 3 design was used to determine the FDG dose that would result in adequate signal for PET-guided therapy. For cohort II, PET imaging data were collected on the X1 system before the first and last fractions among patients undergoing conventional stereotactic body radiation therapy. PET-guided therapy dose distributions were modeled on the patient's computed tomography anatomy using the collected PET data at each fraction as input to an "emulated delivery" and compared with the physician-approved plan. RESULTS: Cohort I demonstrated adequate FDG activity in 6 of 6 evaluable participants (100.0%) with the first injected dose level of 15 mCi FDG. In cohort II, 4 patients with lung tumors and 5 with bone tumors were enrolled, and evaluable emulated delivery data points were collected for 17 treatment fractions. Sixteen of the 17 emulated deliveries resulted in dose distributions that were accurate with respect to the approved PET-guided therapy plan. The 17th data point was just below the 95% threshold for accuracy (dose-volume histogram score = 94.6%). All emulated fluences were physically deliverable. No toxicities were attributed to multiple FDG administrations. CONCLUSIONS: PET-guided therapy is a novel radiation therapy modality in which a radiolabeled tumor can act as its own fiducial for radiation therapy targeting. Emulated therapy dose distributions calculated from continuously acquired real-time PET data were accurate and machine-deliverable in tumors that were 2 to 5 cm in size with adequate FDG signal characteristics.

Image-mode performance characterisation of a positron emission tomography subsystem designed for Biology-guided radiotherapy (BgRT).

OBJECTIVES: In this study, we characterise the imaging-mode performance of the positron emission tomography (PET) subsystem of the RefleXion X1 machine using the NEMA NU-2 2018 standard. METHODS: The X1 machine consists of two symmetrically opposing 900 arcs of PET detectors incorporated into the architecture of a ring-gantry linear accelerator rotating up to 60 RPM. PET emissions from a tumour are detected by the PET detectors and used to guide the delivery of radiation beam. Imaging performance of the PET subsystem on X1 machine was evaluated based on sensitivity of the PET detectors, spatial resolution, count-loss performance, image quality, and daily system performance check. RESULTS: PET subsystem sensitivity was measured as 0.183 and 0.161 cps/kBq at the center and off-center positions, respectively. Spatial resolution: average FWHM values of 4.3, 5.1, and 6.7 mm for the point sources at 1, 10, and 20 cm off center, respectively were recorded. For count loss, max NECR: 2.63 kcps, max true coincidence rate: 5.56 kcps, and scatter fraction: 39.8%. The 10 mm sphere was not visible. Image-quality contrast values were: 29.6%, 64.9%, 66.5%, 81.8%, 81.2%, and background variability: 14.8%, 12.4%, 10.3%, 8.8%, 8.3%, for the 13, 17, 22, 28, 37 mm sphere sizes, respectively. CONCLUSIONS: When operating in an imaging mode, the spatial resolution and image contrast of the X1 PET subsystem were comparable to those of typical diagnostic imaging systems for large spheres, while the sensitivity and count rate were lower due to the significantly smaller PET detector area in the X1 system. Clinical efficacy when used in BgRT remains to be validated. ADVANCES IN KNOWLEDGE: This is the first performance evaluation of the PET subsystem on the novel BgRT machine. The dual arcs rotating PET subsystem on RefleXion X1 machine performance is comparable to those of the typical diagnostic PET system based on the spatial resolution and image contrast for larger spheres.

Aggressive lymphoma in a 14 year old Indian boy, diagnosed on fine needle aspiration cytology.

Burkitt's lymphoma(BL) is a highly aggressive B -cell Lymphoma of childhood with a doubling time of 24 to 48 h. Depending upon the clinical and epidemiological factors it is classified as Epidemic, Sporadic and Immunodeficiency associated Burkitt's lymphoma. Sporadic Burkitt's lymphoma has its own characteristics with few differences pertaining to specific geographical location. Here, we present a case of 14-year-old boy who presented with advanced stage disease. On examination he had cervical lymphadenopathy and CNS involvement in the form of nerve palsy.USG revealed multiple well defined solid lesions in liver, both kidneys and pancreas. However, PBS did not show the presence of lymphomatous cells. Fine needle aspiration cytology (FNAC) of cervical lymph node and liver lesion showed features suggestive of Burkitt's lymphoma, which was further confirmed on Histopathological and immunohistochemical examination.

Performance evaluation of the Ingenuity TF PET/CT scanner with a focus on high count-rate conditions.

This study evaluated the positron emission tomography (PET) imaging performance of the Ingenuity TF 128 PET/computed tomography (CT) scanner which has a PET component that was designed to support a wider radioactivity range than is possible with those of Gemini TF PET/CT and Ingenuity TF PET/MR. Spatial resolution, sensitivity, count rate characteristics and image quality were evaluated according to the NEMA NU 2-2007 standard and ACR phantom accreditation procedures; these were supplemented by additional measurements intended to characterize the system under conditions that would be encountered during quantitative cardiac imaging with (82)Rb. Image quality was evaluated using a hot spheres phantom, and various contrast recovery and noise measurements were made from replicated images. Timing and energy resolution, dead time, and the linearity of the image activity concentration, were all measured over a wide range of count rates. Spatial resolution (4.8-5.1 mm FWHM), sensitivity (7.3 cps kBq(-1)), peak noise-equivalent count rate (124 kcps), and peak trues rate (365 kcps) were similar to those of the Gemini TF PET/CT. Contrast recovery was higher with a 2 mm, body-detail reconstruction than with a 4 mm, body reconstruction, although the precision was reduced. The noise equivalent count rate peak was broad (within 10% of peak from 241-609 MBq). The activity measured in phantom images was within 10% of the true activity for count rates up to those observed in (82)Rb cardiac PET studies.

Design of multiligand inhibitors for the swine flu H1N1 neuraminidase binding site.

Viral neuraminidase inhibitors such as oseltamivir and zanamivir prevent early virus multiplication by blocking sialic acid cleavage on host cells. These drugs are effective for the treatment of a variety of influenza subtypes, including swine flu (H1N1). The binding site for these drugs is well established and they were designed based on computational docking studies. We show here that some common natural products have moderate inhibitory activity for H1N1 neuraminidase under docking studies. Significantly, docking studies using AutoDock for biligand and triligand forms of these compounds (camphor, menthol, and methyl salicylate linked via methylene bridges) indicate that they may bind in combination with high affinity to the H1N1 neuraminidase active site. These results also indicate that chemically linked biligands and triligands of these natural products could provide a new class of drug leads for the prevention and treatment of influenza. This study also highlights the need for a multiligand docking algorithm to understand better the mode of action of natural products, wherein multiple active ingredients are present.

Lead lanthanum zirconate titanate ceramic thin films for energy storage.

An acetic-acid-based sol-gel method was used to deposit lead lanthanum zirconate titanate (PLZT, 8/52/48) thin films on either platinized silicon (Pt/Si) or nickel buffered by a lanthanum nickel oxide buffer layer (LNO/Ni). X-ray diffraction and scanning electron microscopy of the samples revealed that dense polycrystalline PLZT thin films formed without apparent defects or secondary phases. The dielectric breakdown strength was greater in PLZT thin films deposited on LNO/Ni compared with those on Pt/Si, leading to better energy storage. Finally, optimized dielectric properties were determined for a 3-µm-thick PLZT/LNO/Ni capacitor for energy storage purposes: DC dielectric breakdown strength of ∼1.6 MV/cm (480 V), energy density of ∼22 J/cc, energy storage efficiency of ∼77%, and permittivity of ∼1100. These values are very stable from room temperature to 150 °C, indicating that cost-effective, volumetrically efficient capacitors can be fabricated for high-power energy storage.

Rapid diagnosis of Mycobacterium tuberculosis with Truenat MTB: a near-care approach.

BACKGROUND: Control of the global Tuberculosis (TB) burden is hindered by the lack of a simple and effective diagnostic test that can be utilized in resource-limited settings. METHODS: We evaluated the performance of Truenat MTB™, a chip-based nucleic acid amplification test in the detection of Mycobacterium tuberculosis (MTB) in clinical sputum specimens from 226 patients with suspected pulmonary tuberculosis (TB). The test involved sputum processing using Trueprep-MAG™ (nanoparticle-based protocol run on a battery-operated device) and real-time PCR performed on the Truelab Uno™ analyzer (handheld, battery-operated thermal cycler). Specimens were also examined for presence of MTB using smear microscopy, liquid culture and an in-house nested PCR protocol. Results were assessed in comparison to a composite reference standard (CRS) consisting of smear and culture results, clinical treatment and follow-up, and radiology findings. RESULTS: Based on the CRS, 191 patients had "Clinical-TB" (Definite and Probable-TB). Of which 154 patients are already on treatment, and 37 were treatment naïve cases. Remaining 35 were confirmed "Non-TB" cases which are treatment naïve cases. The Truenat MTB test was found to have sensitivity and specificity of 91.1% (CI: 86.1-94.7) and 100% (CI: 90.0-100) respectively, in comparison to 90.58% (CI: 85.5-94.3) and 91.43% (CI: 76.9-98.2) respectively for the in-house nested PCR protocol. CONCLUSION: This preliminary study shows that the Truenat MTB test allows detection of TB in approximately one hour and can be utilized in near-care settings to provide quick and accurate diagnosis.

Pharmacokinetic analysis of hypoxia (18)F-fluoromisonidazole dynamic PET in head and neck cancer.

UNLABELLED: This study used pharmacokinetic analysis of (18)F-labeled fluoromisonidazole ((18)F-FMISO) dynamic PET to assist the identification of regional tumor hypoxia and to investigate the relationship among a potential tumor hypoxia index (K(i)), tumor-to-blood ratio (T/B) in the late-time image, plasma-to-tissue transport rate (k(1)), and local vascular volume fraction (beta) for head and neck cancer patients. METHODS: Newly diagnosed patients underwent a dynamic (18)F-FMISO PET scan before chemotherapy or radiotherapy. The data were acquired in 3 consecutive PET/CT dynamic scan segments, registered with each other and analyzed using pharmacokinetics software. The (K(i), k(1), beta) kinetic parameter images were derived for each patient. RESULTS: Nine patients' data were analyzed. Representative images of (18)F-FDG PET (of the tumor), CT (of the anatomy), and late-time (18)F-FMISO PET (of the T/B) and parametric images of K(i) (potentially representing tumor hypoxia) are shown. The patient image data could be classified into 3 types: with good concordance between the parametric hypoxia map K(i) and high T/B, with concordant findings between the parametric hypoxia map and low T/B, and with ambiguity between parametric hypoxia map and T/B. Correlation coefficients are computed between each pair of T/B, K(i), k(1), and beta. Data are also presented for other potential hypoxia surrogate measures, for example, k(3) and k(1)/k(2). CONCLUSION: There is a positive correlation of 0.86 between the average T/B and average hypoxia index K(i) of the region of interest. However, because of the statistical photon counting noise in PET and the amplification of noise in kinetic analysis, the direct correlation between the T/B and hypoxia of the individual pixel is not obvious. For a tumor region of interest, there is a slight negative correlation between k(1) and K(i), moderate positive correlation between beta and K(i), but no correlation between beta and k(1).

Evaluation of a compartmental model for estimating tumor hypoxia via FMISO dynamic PET imaging.

This paper systematically evaluates a pharmacokinetic compartmental model for identifying tumor hypoxia using dynamic positron emission tomography (PET) imaging with 18F-fluoromisonidazole (FMISO). A generic irreversible one-plasma two-tissue compartmental model was used. A dynamic PET image dataset was simulated with three tumor regions-normoxic, hypoxic and necrotic-embedded in a normal-tissue background, and with an image-based arterial input function. Each voxelized tissue's time activity curve (TAC) was simulated with typical values of kinetic parameters, as deduced from FMISO-PET data from nine head-and-neck cancer patients. The dynamic dataset was first produced without any statistical noise to ensure that correct kinetic parameters were reproducible. Next, to investigate the stability of kinetic parameter estimation in the presence of noise, 1000 noisy samples of the dynamic dataset were generated, from which 1000 noisy estimates of kinetic parameters were calculated and used to estimate the sample mean and covariance matrix. It is found that a more peaked input function gave less variation in various kinetic parameters, and the variation of kinetic parameters could also be reduced by two region-of-interest averaging techniques. To further investigate how bias in the arterial input function affected the kinetic parameter estimation, a shift error was introduced in the peak amplitude and peak location of the input TAC, and the bias of various kinetic parameters calculated. In summary, mathematical phantom studies have been used to determine the statistical accuracy and precision of model-based kinetic analysis, which helps to validate this analysis and provides guidance in planning clinical dynamic FMISO-PET studies.

Isolation and characterisation of bioactive isoflavonoids from the roots of Dalbergia horrida.

The roots of Dalbergia horrida yielded two new isoflavanones, Dalhorridin (I) - 5,5'-dihydroxy-3',4'-methylenedioxy-5''-prenyl-6'',6''-dimethyl-dihydropyrano(2'',3'' : 7,8)-isoflavanone and Dalhorridinin (II) - 5,7,5'-trihydroxy-3',4'-methylenedioxy-8-[5-methyl-2-(2-hydroxyisopropyl)-1,4-hexadienyl]isoflavanone along with two known isoflavones, Dalspinin and Dalspinosin. Preliminary biological screening of the enriched extract revealed that it showed analgesic, anti-inflammatory, CNS depressant and mild anti-bacterial properties.

Two new isoflavonoids from the roots of Dalbergia congesta (Grah).

A systematic examination of the roots of Dalbergia congesta, yielded a new oligomeric isoflavonoid (1), a new tetramethoxy isoflavone (2) along with two known compounds, an isoflavone dalspinin (3) and a benzophenone, cearoin (4). On the basis of chemical and spectral evidences, compounds 1 and 2 were determined to be 5,7-dihydroxy-6,4'-dimethoxy-6'[2''-hydroxy-2''(2''',5'''-dimethoxy neoflavonyl) ethenyl] isoflavone (dalcongestin) and 5,7-dihydroxy-2',3',5',6'-tetramethoxy isoflavone, respectively.

Simultaneous assessment of cardiac perfusion and function using 5-dimensional imaging with Tc-99m teboroxime.

BACKGROUND: Dynamic single photon emission computed tomography (SPECT) acquisition and reconstruction of early poststress technetium 99m teboroxime washout images has been shown to be useful in the detection of coronary disease. Assessment of poststress regional wall motion may offer additional use in assessing coronary disease. Our goal was to investigate the feasibility of simultaneously imaging myocardial ischemia and transient poststress akinesis using gated-dynamic SPECT. METHODS AND RESULTS: A gated-dynamic mathematical cardiac torso (MCAT) phantom was developed to model both teboroxime kinetics and cardiac regional wall motion. A lesion was simulated as having delayed poststress teboroxime washout together with a transient poststress wall motion abnormality. Gated projection data were created to represent a 3-headed SPECT system undergoing a total rotation of 480 degrees . The dynamic expectation-maximization reconstruction algorithm with postsmoothing across gating intervals by Wiener filtering, and the ordered-subset expectation maximization reconstruction algorithm with 3-point smoothing across gating intervals were compared. Compared with the ordered-subset expectation maximization with 3-point smoothing, the dynamic expectation-maximization algorithm with Wiener filtering was able to produce visually higher-quality images and more accurate left ventricular ejection fraction estimates. CONCLUSION: From simulations, we conclude that changing cardiac function and tracer localization possibly can be assessed by using a gated-dynamic acquisition protocol combined with a 5-dimensional reconstruction strategy.

Myocardial perfusion SPECT reconstruction: receiver operating characteristic comparison of CAD detection accuracy of filtered backprojection reconstruction with all of the clinical imaging information available to readers and solely stress slices iteratively reconstructed with combined compensation.

BACKGROUND: Past receiver operating characteristic (ROC) studies have demonstrated that single photon emission computed tomography (SPECT) perfusion imaging by use of iterative reconstruction with combined compensation for attenuation, scatter, and detector response leads to higher area under the ROC curve (A(z)) values for detection of coronary artery disease (CAD) in comparison to the use of filtered backprojection (FBP) with no compensations. A new ROC study was conducted to investigate whether this improvement still holds for iterative reconstruction when observers have available all of the imaging information normally presented to clinical interpreters when reading FBP SPECT perfusion slices. METHODS AND RESULTS: A total of 87 patient studies including 50 patients referred for angiography and 37 patients with a lower than 5% likelihood for CAD were included in the ROC study. The images from the two methods were read by 4 cardiology fellows and 3 attending nuclear cardiologists. Presented for the FBP readings were the short-axis, horizontal long-axis, and vertical long-axis slices for both the stress and rest images; cine images of both the stress and rest projection data; cine images of selected cardiac-gated slices; the CEQUAL-generated stress and rest polar maps; and an indication of patient gender. This was compared with reading solely the iterative reconstructed stress slices with combined compensation for attenuation, scatter, and resolution. With A(z) as the criterion, a 2-way analysis of variance showed a significant improvement in detection accuracy for CAD for the 7 observers (P = .018) for iterative reconstruction with combined compensation (A(z) of 0.895 +/- 0.016) over FBP even with the additional imaging information provided to the observers when scoring the FBP slices (A(z) of 0.869 +/- 0.030). When the groups of 3 attending physicians or 4 cardiology fellows were compared separately, the iterative technique was not statistically significantly better; however, the A(z) for each of the 7 observers individually was larger for iterative reconstruction than for FBP. Compared with results from our previous studies, the additional imaging information did increase the diagnostic accuracy of FBP for CAD but not enough to undo the statistically significantly higher diagnostic accuracy of iterative reconstruction with combined compensation. CONCLUSIONS: We have determined through an ROC investigation that included two classes of observers (experienced attending physicians and cardiology fellows in training) that iterative reconstruction with combined compensation provides statistically significantly better detection accuracy (larger A(z)) for CAD than FBP reconstructions even when the FBP studies were read with all of the extra clinical nuclear imaging information normally available.

Assessment of scatter compensation strategies for (67)Ga SPECT using numerical observers and human LROC studies.

UNLABELLED: 67Ga citrate is an oncologic SPECT imaging agent often used to diagnose or stage patients with non-Hodgkin's lymphoma. As (67)Ga decay involves the emission of multiple-energy gamma-rays, significant photon downscatter will be present within each photopeak energy window. We have previously shown that the inclusion of these scattered photons significantly degrades lesion detectability. The goal of this study was to investigate the extent to which this decrease in detectability can be reversed by applying scatter compensation strategies. METHODS: We have compared 5 different scatter compensation methods to the case of no scatter compensation in iterative SPECT image reconstruction. The strategies consisted of (a). perfect scatter rejection, (b). ideal scatter compensation, (c). triple-energy window (TEW) scatter estimation, (d). effective scatter source estimation (ESSE), and (e). postreconstruction scatter subtraction. Reconstruction parameters used for each method were first optimized using a channelized Hotelling numerical observer. Strategies were then ranked in terms of lesion detectability using a human observer localization receiver operating characteristic (LROC) study. An additional comparison was made comparing the human LROC rankings with a recently developed channelized nonprewhitening (CNPW) LROC numerical observer. RESULTS: Using the area-under-the-LROC-curve (A(LROC)) as the assessment criterion, our results indicate that the TEW and ESSE scatter compensation methods are able to significantly improve lesion detectability over no compensation (A(LROC) = 0.75 and 0.73 vs. 0.67, respectively). However, these compensations failed to achieve the same detectability as perfect scatter rejection (A(LROC) = 0.84). Both ideal scatter compensation and postreconstruction scatter subtraction resulted in numerical increases in detection accuracy that were not statistically significant from no scatter compensation. Good agreement is seen between the CNPW observer and human LROC studies (Spearman rank order coefficient, r(s) = 0.74), thus indicating that the LROC observer may be a good predictor of human observer performance in (67)Ga SPECT. CONCLUSION: Scatter compensation in (67)Ga SPECT imaging using techniques such as TEW or ESSE is able to improve lesion detectability compared with no scatter compensation. A recently developed numerical observer model appears to be a good predictor of human observer performance and may be used to perform imaging optimizations, thereby reducing the need for human LROC studies.

Human-observer receiver-operating-characteristic evaluation of attenuation, scatter, and resolution compensation strategies for (99m)Tc myocardial perfusion imaging.

UNLABELLED: Nonuniform attenuation, scatter, and distance-dependent resolution are confounding factors inherent in SPECT imaging. Iterative reconstruction algorithms permit modeling and compensation of these degradations. We investigated through human-observer receiver-operating-characteristic (ROC) studies which (if any) combination of such compensation strategies best improves the accuracy of detection of coronary artery disease (CAD) when expert readers have only stress images for diagnosis. METHODS: A 3-headed SPECT system fitted with a (153)Gd line source was used to acquire simultaneously (99m)Tc-methoxyisobutylisonitrile (MIBI) images and transmission data. With these acquisitions, the accuracy of detecting CAD was evaluated for the following reconstruction strategies: filtered backprojection (FBP); ordered-subset expectation maximization (OSEM) with attenuation correction (AC); OSEM with AC and scatter correction (SC) (AC + SC); and OSEM with AC, SC, and resolution compensation (RC) (AC + SC + RC). Reconstruction parameters for OSEM were optimized by use of human-observer ROC studies with hybrid images, whereas standard clinical parameters were used for FBP. A total of 100 patients, including 55 patients referred for angiography and 45 patients with <5% likelihood for CAD, were included in the ROC studies. Images reconstructed with the 4 methods were rated independently with regard to the presence of CAD by 7 observers using a continuous scale for certainty. RESULTS: With area under the ROC curve (A(z)) as the criterion, the iterative reconstructions with compensation strategies (AC, AC + SC, and AC + SC + RC) demonstrated better detection accuracy than did FBP reconstructions for the overall detection of CAD as well as for the localization of perfusion defects in the 3 vascular territories. In general, the trend was for an increase in the A(z) for the progression from FBP to OSEM with AC, to OSEM with AC + SC, and to OSEM with AC + SC + RC. Statistically, the combination strategy with AC + SC + RC provided significantly higher A(z) values than did FBP images for the overall detection of CAD and the localization of perfusion defects in the left anterior descending coronary artery and left circumflex coronary artery territories, whereas AC + SC provided significantly better performance in the right coronary artery territory. CONCLUSION: The results indicate that OSEM with AC + SC + RC outperforms FBP reconstructions, indicating that the modeling of physical degradations can improve the accuracy of detection of CAD with cardiac perfusion SPECT reconstructions.

An iterative transmission algorithm incorporating cross-talk correction for SPECT.

Simultaneous emission/transmission acquisitions in cardiac SPECT with a Tc99m/Gd153 source combination offer the capability for nonuniform attenuation correction. However, cross-talk of Tc99m photons downscattered into the Gd153 energy window contaminates the reconstructed transmission map used for attenuation correction. The estimated cross-talk contribution can be subtracted prior to transmission reconstruction or incorporated in the reconstruction algorithm itself. In this work, we propose an iterative transmission algorithm (MLTG-S) based on the maximum-likelihood gradient algorithm (MLTG) that explicitly accounts for this cross-talk estimate. Clinical images were acquired on a three-headed SPECT camera, acquiring Tc99m emission and Gd153 transmission images simultaneously. Subtracting the cross-talk estimate prior to transmission reconstruction can result in negative and zero values if the estimate is larger than or equal to the count in the transmission projection bin, especially with increased attenuator size or amount of cross-talk. This results in inaccurate attenuation coefficients for MLTG reconstructions with cross-talk subtraction. MLTG-S reconstructions on the other hand, yield better estimates of attenuation maps, by avoiding the subtraction of the cross-talk estimate. Comparison of emission slices corrected for nonuniform attenuation reveals that inaccuracies in the reconstructed attenuation map caused by cross-talk can artificially enhance the extra-cardiac activity, confounding the ability to visualize the left-ventricular walls.