Myocardial perfusion imaging (MPI) using single-photon emission computed tomography (SPECT) is a well-established modality for noninvasive diagnostic assessment of coronary artery disease (CAD). However, the time-consuming and experience-dependent visual interpretation of SPECT images remains a limitation in the clinic. We aimed to develop advanced models to diagnose CAD using different supervised and semi-supervised deep learning (DL) algorithms and training strategies, including transfer learning and data augmentation, with SPECT-MPI and invasive coronary angiography (ICA) as standard of reference. A total of 940 patients who underwent SPECT-MPI were enrolled (281 patients included ICA). Quantitative perfusion SPECT (QPS) was used to extract polar maps of rest and stress states. We defined two different tasks, including (1) Automated CAD diagnosis with expert reader (ER) assessment of SPECT-MPI as reference, and (2) CAD diagnosis from SPECT-MPI based on reference ICA reports. In task 2, we used 6 strategies for training DL models. We implemented 13 different DL models along with 4 input types with and without data augmentation (WAug and WoAug) to train, validate, and test the DL models (728 models). One hundred patients with ICA as standard of reference (the same patients in task 1) were used to evaluate models per vessel and per patient. Metrics, such as the area under the receiver operating characteristics curve (AUC), accuracy, sensitivity, specificity, precision, and balanced accuracy were reported. DeLong and pairwise Wilcoxon rank sum tests were respectively used to compare models and strategies after 1000 bootstraps on the test data for all models. We also compared the performance of our best DL model to ER's diagnosis. In task 1, DenseNet201 Late Fusion (AUC = 0.89) and ResNet152V2 Late Fusion (AUC = 0.83) models outperformed other models in per-vessel and per-patient analyses, respectively. In task 2, the best models for CAD prediction based on ICA were Strategy 3 (a combination of ER- and ICA-based diagnosis in train data), WoAug InceptionResNetV2 EarlyFusion (AUC = 0.71), and Strategy 5 (semi-supervised approach) WoAug ResNet152V2 EarlyFusion (AUC = 0.77) in per-vessel and per-patient analyses, respectively. Moreover, saliency maps showed that models could be helpful for focusing on relevant spots for decision making. Our study confirmed the potential of DL-based analysis of SPECT-MPI polar maps in CAD diagnosis. In the automation of ER-based diagnosis, models' performance was promising showing accuracy close to expert-level analysis. It demonstrated that using different strategies of data combination, such as including those with and without ICA, along with different training methods, like semi-supervised learning, can increase the performance of DL models. The proposed DL models could be coupled with computer-aided diagnosis systems and be used as an assistant to nuclear medicine physicians to improve their diagnosis and reporting, but only in the LAD territory. Not applicable.

Convolutional neural networks (CNNs) have been studied for detecting bone metastases on bone scans; however, the application of ConvNeXt and transformer models has not yet been explored. This study aims to evaluate the performance of various deep learning models, including the ConvNeXt and transformer models, in diagnosing metastatic lesions from bone scans. We retrospectively analyzed bone scans from patients with cancer obtained at 2 institutions: the training and validation sets (n=4626) were from Hospital 1 and the test set (n=1428) was from Hospital 2. The deep learning models evaluated included ResNet18, the Data-Efficient Image Transformer (DeiT), the Vision Transformer (ViT Large 16), the Swin Transformer (Swin Base), and ConvNeXt Large. Gradient-weighted class activation mapping (Grad-CAM) was used for visualization. Both the validation set and the test set demonstrated that the ConvNeXt large model (0.969 and 0.885, respectively) exhibited the best performance, followed by the Swin Base model (0.965 and 0.840, respectively), both of which significantly outperformed ResNet (0.892 and 0.725, respectively). Subgroup analyses revealed that all the models demonstrated greater diagnostic accuracy for patients with polymetastasis compared with those with oligometastasis. Grad-CAM visualization revealed that the ConvNeXt Large model focused more on identifying local lesions, whereas the Swin Base model focused on global areas such as the axial skeleton and pelvis. Compared with traditional CNN and transformer models, the ConvNeXt model demonstrated superior diagnostic performance in detecting bone metastases from bone scans, especially in cases of polymetastasis, suggesting its potential in medical image analysis.

Quantitative measures of dopamine transporter (DaT) uptake in caudate, putamen, and globus pallidus derived from DaT-single-photon emission computed tomography (SPECT) images are being investigated as biomarkers to diagnose, assess disease status, and track the progression of Parkinsonism. Reliable quantification from DaT-SPECT images requires performing attenuation compensation (AC), typically with a separate X-ray CT scan. Such CT-based AC (CTAC) has multiple challenges, a key one being the non-availability of X-ray CT component on many clinical SPECT systems. Even when a CT is available, the additional CT scan leads to increased radiation dose, costs, and complexity, potential quantification errors due to SPECT-CT misalignment, and higher training and regulatory requirements. To overcome the challenges with the requirement of a CT scan for AC in DaT SPECT, we propose a deep learning (DL)-based transmission-less AC method for DaT-SPECT (DaT-CTLESS). An in silico imaging trial, titled ISIT-DaT, was designed to evaluate the performance of DaT-CTLESS on the regional uptake quantification task. We observed that DaT-CTLESS yielded a significantly higher correlation with CTAC than that between UAC and CTAC on the regional DaT uptake quantification task. Further, DaT-CLTESS had an excellent agreement with CTAC on this task, significantly outperformed UAC in distinguishing patients with normal versus reduced putamen SBR, yielded good generalizability across two scanners, was generally insensitive to intra-regional uptake heterogeneity, demonstrated good repeatability, exhibited robust performance even as the size of the training data was reduced, and generally outperformed the other considered DL methods on the task of quantifying regional uptake across different training dataset sizes. These results provide a strong motivation for further clinical evaluation of DaT-CTLESS.

PURPOSECardiac amyloidosis (CA), a life-threatening infiltrative cardiomyopathy, can be non-invasively diagnosed using [99mTc]Tc-bisphosphonate SPECT/CT. However, subjective visual interpretation risks diagnostic inaccuracies. We developed and validated a machine learning (ML) framework leveraging SPECT/CT radiomics to automate CA detection. METHODSThis retrospective multicenter study analyzed 290 patients of suspected CA who underwent [99mTc]Tc-PYP or [99mTc]Tc-DPD SPECT/CT. Radiomic features were extracted from co-registered SPECT and CT images, harmonized via intra-class correlation and Pearson correlation filtering, and optimized through LASSO regression. A stacking ensemble model incorporating support vector machine (SVM), random forest (RF), gradient boosting decision tree (GBDT), and adaptive boosting (AdaBoost) classifiers was constructed. The model was validated using an internal validation set (n = 54) and two external test set (n = 54 and n = 58).Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), calibration, and decision curve analysis (DCA). Feature importance was interpreted using SHapley Additive exPlanations (SHAP) values. RESULTSOf 290 patients, 117 (40.3%) had CA. The stacking radiomics model attained AUCs of 0.871, 0.824, and 0.839 in the validation, test 1, and test 2 cohorts, respectively, significantly outperforming the clinical model (AUC 0.546 in validation set, P<0.05). DCA demonstrated superior net benefit over the clinical model across relevant thresholds, and SHAP analysis highlighted wavelet-transformed first-order and texture features as key predictors. CONCLUSIONA stacking ML model with SPECT/CT radiomics improves CA diagnosis, showing strong generalizability across varied imaging protocols and populations and highlighting its potential as a decision-support tool.

Background and AimsRevascularization in stable coronary artery disease often relies on ischemia severity, but we introduce an AI-driven approach that uses clinical and imaging data to estimate individualized treatment effects and guide personalized decisions. MethodsUsing a large, international registry from 13 centers, we developed an AI model to estimate individual treatment effects by simulating outcomes under alternative therapeutic strategies. The model was trained on an internal cohort constructed using 1:1 propensity score matching to emulate randomized controlled trials (RCTs), creating balanced patient pairs in which only the treatment strategy--early revascularization (defined as any procedure within 90 days of MPI) versus medical therapy--differed. This design allowed the model to estimate individualized treatment effects, forming the basis for counterfactual reasoning at the patient level. We then derived the AI-REVASC score, which quantifies the potential benefit, for each patient, of early revascularization. The score was validated in the held-out testing cohort using Cox regression. ResultsOf 45,252 patients, 19,935 (44.1%) were female, median age 65 (IQR: 57-73). During a median follow-up of 3.6 years (IQR: 2.7-4.9), 4,323 (9.6%) experienced MI or death. The AI model identified a group (n=1,335, 5.9%) that benefits from early revascularization with a propensity-adjusted hazard ratio of 0.50 (95% CI: 0.25-1.00). Patients identified for early revascularization had higher prevalence of hypertension, diabetes, dyslipidemia, and lower LVEF. ConclusionsThis study pioneers a scalable, data-driven approach that emulates randomized trials using retrospective data. The AI-REVASC score enables precision revascularization decisions where guidelines and RCTs fall short. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=104 SRC="FIGDIR/small/25329295v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): [email protected]@1df75d8org.highwire.dtl.DTLVardef@1b1ce68org.highwire.dtl.DTLVardef@663cdf_HPS_FORMAT_FIGEXP M_FIG C_FIG

BackgroundImpulse control disorders (ICD) in Parkinsons disease (PD) patients mainly occur as adverse effects of dopamine replacement therapy. Despite several known risk factors associated with ICD development, this cannot yet be accurately predicted at PD diagnosis. ObjectivesWe aimed to investigate the predictability of incident ICD by baseline measures of demographic, clinical, dopamine transporter single photon emission computed tomography (DAT-SPECT), and genetic variables. MethodsWe used demographic and clinical data of medication-free PD patients from two longitudinal datasets; Parkinsons Progression Markers Initiative (PPMI) (n=311) and Amsterdam UMC (n=72). We extracted radiomic and latent features from DAT-SPECT. We used single nucleotic polymorphisms (SNPs) from PPMIs NeuroX and Exome sequencing data. Four machine learning classifiers were trained on combinations of the input feature sets, to predict incident ICD at any follow-up assessment. Classification performance was measured with 10x5-fold cross-validation. ResultsICD prevalence at any follow-up was 0.32. The highest performance in predicting incident ICD (AUC=0.66) was achieved by the models trained on clinical features only. Anxiety severity and age of PD onset were identified as the most important features. Performance did not improve with adding features from DAT-SPECT or SNPs. We observed significantly higher performance (AUC=0.74) when classifying patients who developed ICD within four years from diagnosis compared with those tested negative for seven or more years. ConclusionsPrediction accuracy for later ICD development, at the time of PD diagnosis, is limited; however, it increases for shorter time-to-event predictions. Neither DAT-SPECT nor genetic data improve the predictability obtained using demographic and clinical variables alone.

Advancements of deep learning in medical imaging are often constrained by the limited availability of large, annotated datasets, resulting in underperforming models when deployed under real-world conditions. This study investigated a generative artificial intelligence (AI) approach to create synthetic medical images taking the example of bone scintigraphy scans, to increase the data diversity of small-scale datasets for more effective model training and improved generalization. We trained a generative model on ^99mTc-bone scintigraphy scans from 9,170 patients in one center to generate high-quality and fully anonymized annotated scans of patients representing two distinct disease patterns: abnormal uptake indicative of (i) bone metastases and (ii) cardiac uptake indicative of cardiac amyloidosis. A blinded reader study was performed to assess the clinical validity and quality of the generated data. We investigated the added value of the generated data by augmenting an independent small single-center dataset with synthetic data and by training a deep learning model to detect abnormal uptake in a downstream classification task. We tested this model on 7,472 scans from 6,448 patients across four external sites in a cross-tracer and cross-scanner setting and associated the resulting model predictions with clinical outcomes. The clinical value and high quality of the synthetic imaging data were confirmed by four readers, who were unable to distinguish synthetic scans from real scans (average accuracy: 0.48% [95% CI 0.46-0.51]), disagreeing in 239 (60%) of 400 cases (Fleiss' kappa: 0.18). Adding synthetic data to the training set improved model performance by a mean (± SD) of 33(± 10)% AUC (p < 0.0001) for detecting abnormal uptake indicative of bone metastases and by 5(± 4)% AUC (p < 0.0001) for detecting uptake indicative of cardiac amyloidosis across both internal and external testing cohorts, compared to models without synthetic training data. Patients with predicted abnormal uptake had adverse clinical outcomes (log-rank: p < 0.0001). Generative AI enables the targeted generation of bone scintigraphy images representing different clinical conditions. Our findings point to the potential of synthetic data to overcome challenges in data sharing and in developing reliable and prognostic deep learning models in data-limited environments.

VSBONE^® BSI (VSBONE), an automated bone scan index (BSI) measurement system was updated from version 2.1 (ver.2) to 3.0 (ver.3). VSBONE ver.3 incorporates deep learning of the skeletal structures of 957 new women, and it can be applied in patients with breast cancer. However, the performance of the updated VSBONE remains unclear. This study aimed to validate the diagnostic accuracy of the VSBONE system in patients with breast cancer. In total, 220 Japanese patients with breast cancer who underwent bone scintigraphy with single-photon emission computed tomography/computed tomography (SPECT/CT) were retrospectively analyzed. The patients were diagnosed with active bone metastases (<i>n</i> = 20) and non-bone metastases (<i>n</i> = 200) according to the physician's radiographic image interpretation. The patients were assessed using the VSBONE ver.2 and VSBONE ver.3, and the BSI findings were compared with the interpretation results by the physicians. The occurrence of segmentation errors, the association of BSI between VSBONE ver.2 and VSBONE ver.3, and the diagnostic accuracy of the systems were evaluated. VSBONE ver.2 and VSBONE ver.3 had segmentation errors in four and two patients. Significant positive linear correlations were confirmed in both versions of the BSI (<i>r</i> = 0.92). The diagnostic accuracy was 54.1% in VSBOBE ver.2, and 80.5% in VSBONE ver.3 <i>(P</i> < 0.001), respectively. The diagnostic accuracy of VSBONE was improved through deep learning of the female skeletal structures. The updated VSBONE ver.3 can be a reliable automated system for measuring BSI in patients with breast cancer.

Fragile X Syndrome (FXS) is a rare neurodevelopmental disorder caused by a trinucleotide repeat expansion on the 5 untranslated region of the FMR1 gene. FXS is characterized by intellectual disability, anxiety, sensory hypersensitivity, and difficulties with executive function. A recent phase 2 placebo-controlled clinical trial assessing BPN14770, a first-in-class phosphodiesterase 4D allosteric inhibitor, in 30 adult males (age 18-41 years) with FXS demonstrated cognitive improvements on the NIH Toolbox Cognitive Battery in domains related to language and caregiver reports of improvement in both daily functioning and language. However, individual physiological measures from electroencephalography (EEG) demonstrated only marginal significance for trial efficacy. A secondary analysis of resting state EEG data collected as part of the phase 2 clinical trial evaluating BPN14770 was conducted using a machine learning classification algorithm to classify trial conditions (i.e., baseline, drug, placebo) via linear EEG variable combinations. The algorithm identified a composite of peak alpha frequencies (PAF) across multiple brain regions as a potential biomarker demonstrating BPN14770 efficacy. Increased PAF from baseline was associated with drug but not placebo. Given the relationship between PAF and cognitive function among typically developed adults and those with intellectual disability, as well as previously reported reductions in alpha frequency and power in FXS, PAF represents a potential physiological measure of BPN14770 efficacy.

Artificial intelligence (AI), particularly machine learning (ML) and deep learning (DL), has significant potential to advance the capabilities of nuclear neuroimaging. The current and emerging applications of ML and DL in the processing, analysis, enhancement and interpretation of SPECT and PET imaging are explored for brain imaging. Key developments include automated image segmentation, disease classification, and radiomic feature extraction, including lower dimensionality first and second order radiomics, higher dimensionality third order radiomics and more abstract fourth order deep radiomics. DL-based reconstruction, attenuation correction using pseudo-CT generation, and denoising of low-count studies have a role in enhancing image quality. AI has a role in sustainability through applications in radioligand design and preclinical imaging while federated learning addresses data security challenges to improve research and development in nuclear cerebral imaging. There is also potential for generative AI to transform the nuclear cerebral imaging space through solutions to data limitations, image enhancement, patient-centered care, workflow efficiencies and trainee education. Innovations in ML and DL are re-engineering the nuclear neuroimaging ecosystem and reimagining tomorrow's precision medicine landscape.