Evaluation of the effect of reducing administered activity on assessment of function in cardiac gated SPECT.

BACKGROUND: We previously optimized several reconstruction strategies in SPECT myocardial perfusion imaging (MPI) with low dose for perfusion-defect detection. Here we investigate whether reducing the administered activity can also maintain the diagnostic accuracy in evaluating cardiac function. METHODS: We quantified the myocardial motion in cardiac-gated stress 99m-Tc-sestamibi SPECT studies from 163 subjects acquired with full dose (29.8 ± 3.6 mCi), and evaluated the agreement of the obtained motion/thickening and ejection fraction (EF) measures at various reduced dose levels (uniform reduction or personalized dose) with that at full dose. We also quantified the detectability of abnormal motion via a receiver-operating characteristics (ROC) study. For reconstruction we considered both filtered backprojection (FBP) without correction for degradations, and iterative ordered-subsets expectation-maximization (OS-EM) with resolution, attenuation and scatter corrections. RESULTS: With dose level lowered to 25% of full dose, the obtained results on motion/thickening, EF and abnormal motion detection were statistically comparable to full dose in both reconstruction strategies, with Pearson's r > 0.9 for global motion measures between low dose and full dose. CONCLUSIONS: The administered activity could be reduced to 25% of full dose without degrading the function assessment performance. Low dose reconstruction optimized for perfusion-defect detection can be reasonable for function assessment in gated SPECT.

Investigation of dose reduction in cardiac perfusion SPECT via optimization and choice of the image reconstruction strategy.

BACKGROUND: We investigated the extent to which the administered dose (activity) level can be reduced without sacrificing diagnostic accuracy for three reconstruction strategies for SPECT-myocardial perfusion imaging (MPI). METHODS: We optimized the parameters of the three reconstruction strategies for perfusion-defect detection over a range of simulated administered dose levels using a set of hybrid studies (derived from 190 subjects) consisting of clinical SPECT-MPI data modified to contain realistic simulated lesions. The optimized strategies we considered are filtered backprojection (FBP) with no correction for degradations, ordered-subsets expectation-maximization (OS-EM) with attenuation correction (AC), scatter correction (SC), and resolution correction (RC), and OS-EM with scatter and resolution correction only. Each study was evaluated using a total perfusion deficit (TPD) score computed by the Quantitative Perfusion SPECT (QPS) software package. We conducted a receiver operating characteristics (ROC) study based on the TPD scores for each dose level and reconstruction strategy. RESULTS: For FBP, the achieved optimum values of the area under the ROC curve (AUC) at 100%, 50%, 25%, and 12.5% of standard dose were 0.75, 0.74, 0.72, and 0.70, respectively, compared to 0.81, 0.79, 0.76, and 0.74 for OS-EM with AC-SC-RC and 0.78, 0.77, 0.74, 0.72 for OS-EM with SC-RC. CONCLUSIONS: Our results suggest that studies reconstructed by OS-EM with AC-SC-RC could possibly be reduced, on average, to 25% of the originally administered dose without causing diagnostic accuracy (AUC) to decrease below that of FBP.

Development and deployment of a histopathology-based deep learning algorithm for patient prescreening in a clinical trial.

Accurate identification of genetic alterations in tumors, such as Fibroblast Growth Factor Receptor, is crucial for treating with targeted therapies; however, molecular testing can delay patient care due to the time and tissue required. Successful development, validation, and deployment of an AI-based, biomarker-detection algorithm could reduce screening cost and accelerate patient recruitment. Here, we develop a deep-learning algorithm using >3000 H&E-stained whole slide images from patients with advanced urothelial cancers, optimized for high sensitivity to avoid ruling out trial-eligible patients. The algorithm is validated on a dataset of 350 patients, achieving an area under the curve of 0.75, specificity of 31.8% at 88.7% sensitivity, and projected 28.7% reduction in molecular testing. We successfully deploy the system in a non-interventional study comprising 89 global study clinical sites and demonstrate its potential to prioritize/deprioritize molecular testing resources and provide substantial cost savings in the drug development and clinical settings.

Personalized Models for Injected Activity Levels in SPECT Myocardial Perfusion Imaging.

We propose a patient-specific ("personalized") approach for tailoring the injected activities to individual patients in order to achieve dose reduction in SPECT-myocardial perfusion imaging (MPI). First, we develop a strategy to determine the minimum dose levels required for each patient in a large set of clinical acquisitions (857 subjects) such that the reconstructed images are sufficiently similar to that obtained at conventional clinical dose. We then apply machine learning models to predict the required dose levels on an individual basis based on a set of patient attributes which include body measurements and various clinical variables. We demonstrate the personalized dose models for two commonly used reconstruction methods in clinical SPECT-MPI: 1) conventional filtered backprojection (FBP) with post-filtering and 2) ordered-subsets expectation-maximization (OS-EM) with corrections for attenuation, scatter and resolution, and evaluate their performance in perfusion-defect detection by using the clinical Quantitative Perfusion SPECT software package. The results indicate that the achieved dose reduction can vary greatly among individuals from their conventional clinical dose and that the personalized dose models can achieve further reduction on average compared with a global (non-patient specific) dose reduction approach. In particular, the average personalized dose level can be reduced to 58% and 54% of the full clinical dose, respectively, for FBP and OS-EM reconstruction, while without deteriorating the accuracy in perfusion-defect detection. Furthermore, with the average personalized dose further reduced to only 16% of full dose, OS-EM can still achieve a detection accuracy level comparable to that of FBP with full dose.