This study aims to assess the added value of utilizing short-dynamic whole-body PET/CT scans and implementing motion correction before quantifying metabolic rate, offering more insights into physiological processes. While this approach may not be commonly adopted, addressing motion effects is crucial due to their demonstrated potential to cause significant errors in parametric imaging. A 15-minute dynamic FDG PET acquisition protocol was utilized for four lymphoma patients undergoing therapy evaluation. Parametric imaging was obtained using a population-based input function (PBIF) derived from twelve patients with full 65-minute dynamic FDG PET acquisition. AI-based registration methods were employed to correct misalignments between both PET and ACCT and PET-to-PET. Tumour characteristics were assessed using both parametric images and standardized uptake values (SUV). The motion correction process significantly reduced mismatches between images without significantly altering voxel intensity values, except for SUV_max. Following the alignment of the attenuation correction map with the PET frame, an increase in SUV_max in FDG-avid lymph nodes was observed, indicating its susceptibility to spatial misalignments. In contrast, Patlak K_i parameter was highly sensitive to misalignment across PET frames, that notably altered the Patlak slope. Upon completion of the motion correction process, the parametric representation revealed heterogeneous behaviour among lymph nodes compared to SUV images. Notably, reduced volume of elevated metabolic rate was determined in the mediastinal lymph nodes in contrast with an SUV of 5 g/ml, indicating potential perfusion or inflammation. Motion resolved short-dynamic PET can enhance the utility and reliability of parametric imaging, an aspect often overlooked in commercial software.

Attenuation correction (AC) is necessary for accurate activity quantification in positron emission tomography (PET). Conventional reconstruction methods typically rely on attenuation maps derived from a co-registered computed tomography (CT) or magnetic resonance imaging scan. However, this additional scan may complicate the imaging workflow, introduce misalignment artifacts and increase radiation exposure. In this paper, we propose a joint reconstruction of activity and attenuation (JRAA) approach that eliminates the need for auxiliary anatomical imaging by relying solely on emission data. This framework combines wavelet diffusion model (WDM) and diffusion posterior sampling (DPS) to reconstruct fully three-dimensional (3-D) data. Experimental results show our method outperforms maximum likelihood activity and attenuation (MLAA) and MLAA with UNet-based post processing, and yields high-quality noise-free reconstructions across various count settings when time-of-flight (TOF) information is available. It is also able to reconstruct non-TOF data, although the reconstruction quality significantly degrades in low-count (LC) conditions, limiting its practical effectiveness in such settings. This approach represents a step towards stand-alone PET imaging by reducing the dependence on anatomical modalities while maintaining quantification accuracy, even in low-count scenarios when TOF information is available.

Accurate differentiation of the histologic invasiveness of early-stage lung adenocarcinoma is crucial for determining surgical strategies. This study aimed to investigate the potential of [⁶⁸Ga]Ga-FAPI-46 PET/CT in assessing the invasiveness of early lung adenocarcinoma presenting as ground-glass nodules (GGNs) and identifying imaging features with strong predictive potential. This prospective study (NCT04588064) was conducted between July 2020 and July 2022, focusing on GGNs that were confirmed postoperatively to be either invasive adenocarcinoma (IAC), minimally invasive adenocarcinoma (MIA), or precursor glandular lesions (PGL). A total of 45 patients with 53 pulmonary GGNs were included in the study: 19 patients with GGNs associated with PGL-MIA and 34 with IAC. Lung nodules were segmented using the Segment Anything Model in Medical Images (MedSAM) and the PET Tumor Segmentation Extension. Clinical characteristics, along with conventional and high-throughput radiomics features from High-resolution CT (HRCT) and PET scans, were analysed. The predictive performance of these features in differentiating between PGL or MIA (PGL-MIA) and IAC was assessed using 5-fold cross-validation across six machine learning algorithms. Model validation was performed on an independent external test set (n = 11). The Chi-squared, Fisher's exact, and DeLong tests were employed to compare the performance of the models. The maximum standardised uptake value (SUVmax) derived from [⁶⁸Ga]Ga-FAPI-46 PET was identified as an independent predictor of IAC. A cut-off value of 1.82 yielded a sensitivity of 94% (32/34), specificity of 84% (16/19), and an overall accuracy of 91% (48/53) in the training set, while achieving 100% (12/12) accuracy in the external test set. Radiomics-based classification further improved diagnostic performance, achieving a sensitivity of 97% (33/34), specificity of 89% (17/19), accuracy of 94% (50/53), and an area under the receiver operating characteristic curve (AUC) of 0.97 [95% CI: 0.93-1.00]. Compared with the CT-based radiomics model and the PET-based model, the combined PET/CT radiomics model did not show significant improvement in predictive performance. The key predictive feature was [⁶⁸Ga]Ga-FAPI-46 PET log-sigma-7-mm-3D_firstorder_RootMeanSquared. The SUVmax derived from [⁶⁸Ga]Ga-FAPI-46 PET/CT can effectively differentiate the invasiveness of early-stage lung adenocarcinoma manifesting as GGNs. Integrating high-throughput features from [⁶⁸Ga]Ga-FAPI-46 PET/CT images can considerably enhance classification accuracy. NCT04588064; URL: https://clinicaltrials.gov/study/NCT04588064 .

Quantifying biological parameters of interest through dynamic positron emission tomography (PET) requires an arterial input function (AIF) conventionally obtained from arterial blood samples. The AIF can also be non-invasively estimated from blood pools in PET images, often identified using co-registered MRI images. Deploying methods without blood sampling or the use of MRI generally requires total body PET systems with a long axial field-of-view (LAFOV) that includes a large cardiovascular blood pool. However, the number of such systems in clinical use is currently much smaller than that of short axial field-of-view (SAFOV) scanners. We propose a data-driven approach for AIF estimation for SAFOV PET scanners, which is non-invasive and does not require MRI or blood sampling using brain PET scans. The proposed method was validated using dynamic ¹⁸F-fluorodeoxyglucose [¹⁸F]FDG total body PET data from 10 subjects. A variational inference-based machine learning approach was employed to correct for peak activity. The prior was estimated using a probabilistic vascular MRI atlas, registered to each subject's PET image to identify cerebral arteries in the brain. The estimated AIF using brain PET images (IDIF-Brain) was compared to that obtained using data from the descending aorta of the heart (IDIF-DA). Kinetic rate constants (K₁, k₂, k₃) and net radiotracer influx (K_i) for both cases were computed and compared. Qualitatively, the shape of IDIF-Brain matched that of IDIF-DA, capturing information on both the peak and tail of the AIF. The area under the curve (AUC) of IDIF-Brain and IDIF-DA were similar, with an average relative error of 9%. The mean Pearson correlations between kinetic parameters (K₁, k₂, k₃) estimated with IDIF-DA and IDIF-Brain for each voxel were between 0.92 and 0.99 in all subjects, and for K_i, it was above 0.97. This study introduces a new approach for AIF estimation in dynamic PET using brain PET images, a probabilistic vascular atlas, and machine learning techniques. The findings demonstrate the feasibility of non-invasive and subject-specific AIF estimation for SAFOV scanners.

Dynamic FDG PET imaging study of n = 52 rats including 26 control Wistar-Kyoto (WKY) rats and 26 experimental spontaneously hypertensive rats (SHR) were performed using a Siemens microPET and Albira trimodal scanner longitudinally at 1, 2, 3, 5, 9, 12 and 18 months of age. A 15-parameter dual output model correcting for spill over contamination and partial volume effects with peak fitting cost functions was developed for simultaneous estimation of model corrected blood input function (MCIF) and kinetic rate constants for dynamic FDG PET images of rat heart in vivo. Major drawbacks of this model are its dependence on manual annotations for the Image Derived Input Function (IDIF) and manual determination of crucial model parameters to compute MCIF. To overcome these limitations, we performed semi-automated segmentation and then formulated a Long-Short-Term Memory (LSTM) cell network to train and predict MCIF in test data using a concatenation of IDIFs and myocardial inputs and compared them with reference-modeled MCIF. Thresholding along 2D plane slices with two thresholds, with T1 representing high-intensity myocardium, and T2 representing lower-intensity rings, was used to segment the area of the LV blood pool. The resultant IDIF and myocardial TACs were used to compute the corresponding reference (model) MCIF for all data sets. The segmented IDIF and the myocardium formed the input for the LSTM network. A k-fold cross validation structure with a 33:8:11 split and 5 folds was utilized to create the model and evaluate the performance of the LSTM network for all datasets. To overcome the sparseness of data as time steps increase, midpoint interpolation was utilized to increase the density of datapoints beyond time = 10 minutes. The model utilizing midpoint interpolation was able to achieve a 56.4% improvement over previous Mean Squared Error (MSE).

The recent approval of anti-amyloid pharmaceuticals for the treatment of Alzheimer's disease (AD) has created a pressing need for the ability to accurately identify optimal candidates for anti-amyloid therapy, specifically those with evidence for incipient cognitive decline, since patients with mild cognitive impairment (MCI) may remain stable for several years even with positive AD biomarkers. Using fluorodeoxyglucose PET and biomarker data from 594 ADNI patients, a neural network ensemble was trained to forecast cognition from MCI diagnostic baseline. Training data comprised PET studies of patients with biological AD. The ensemble discriminated between progressive and stable prodromal subjects (MCI with positive amyloid and tau) at baseline with 88.6% area-under-curve, 88.6% (39/44) accuracy, 73.7% (14/19) sensitivity and 100% (25/25) specificity in the test set. It also correctly classified all other test subjects (healthy or AD continuum subjects across the cognitive spectrum) with 86.4% accuracy (206/239), 77.4% sensitivity (33/42) and 88.23% (165/197) specificity. By identifying patients with prodromal AD who will not progress to dementia, our model could significantly reduce overall societal burden and cost if implemented as a screening tool. The model's high positive predictive value in the prodromal test set makes it a practical means for selecting candidates for anti-amyloid therapy and trials.

Positron Emission Tomography (PET) is an important clinical imaging tool but inevitably introduces radiation exposure to patients and healthcare providers. Reducing the tracer injection dose and eliminating the CT acquisition for attenuation correction can reduce the overall radiation dose, but often results in PET with high noise and bias. Thus, it is desirable to develop 3D methods to translate the non-attenuation-corrected low-dose PET (NAC-LDPET) into attenuation-corrected standard-dose PET (AC-SDPET). Recently, diffusion models have emerged as a new state-of-the-art deep learning method for image-to-image translation, better than traditional CNN-based methods. However, due to the high computation cost and memory burden, it is largely limited to 2D applications. To address these challenges, we developed a novel 2.5D Multi-view Averaging Diffusion Model (MADM) for 3D image-to-image translation with application on NAC-LDPET to AC-SDPET translation. Specifically, MADM employs separate diffusion models for axial, coronal, and sagittal views, whose outputs are averaged in each sampling step to ensure the 3D generation quality from multiple views. To accelerate the 3D sampling process, we also proposed a strategy to use the CNN-based 3D generation as a prior for the diffusion model. Our experimental results on human patient studies suggested that MADM can generate high-quality 3D translation images, outperforming previous CNN-based and Diffusion-based baseline methods. The code is available at https://github.com/tianqic/MADM.

Biochemical recurrence (BCR) after radical prostatectomy exhibits heterogeneous prognostic implications. Recent advancements in imaging and biomarkers have high potential for personalizing care. Prostate-specific membrane antigen imaging (PSMA)-PET/CT has revolutionized the BCR management in prostate cancer by detecting microscopic lesions earlier than conventional staging, leading to improved cancer control outcomes and changes in treatment plans in approximately two-thirds of cases. Salvage radiotherapy, often combined with androgen deprivation therapy, remains the standard treatment for high-risk BCR postprostatectomy, with PSMA-PET/CT guiding treatment adjustments, such as the radiation field, and improving progression-free survival. Advancements in biomarkers, genomic classifiers, and artificial intelligence-based models have enhanced risk stratification and personalized treatment planning, resulting in both treatment intensification and de-escalation. While conventional risk grouping relying on Gleason score and PSA level and kinetics remain the foundation for BCR management, PSMA-PET/CT, novel biomarkers, and artificial intelligence may enable more personalized treatment strategies.

According to the updated classification system, human epidermal growth factor receptor 2 (HER2) expression statuses are divided into the following three groups: HER2-over-expression, HER2-low-expression, and HER2-zero-expression. HER2-negative expression was reclassified into HER2-low-expression and HER2-zero-expression. This study aimed to identify three different HER2 expression statuses for breast cancer (BC) patients using PET/CT radiomics and clinicopathological characteristics. A total of 315 BC patients who met the inclusion and exclusion criteria from two institutions were retrospectively included. The patients in institution 1 were divided into the training set and the independent validation set according to the ratio of 7:3, and institution 2 was used as the external validation set. According to the results of pathological examination, all BC patients were divided into HER2-over-expression, HER2-low-expression, and HER2-zero-expression. First, PET/CT radiomic features and clinicopathological features based on each patient were extracted and collected. Second, multiple methods were used to perform feature screening and feature selection. Then, four machine learning classifiers, including logistic regression (LR), k-nearest neighbor (KNN), support vector machine (SVM), and random forest (RF), were constructed to identify HER2-over-expression vs. others, HER2-low-expression vs. others, and HER2-zero-expression vs. others. The receiver operator characteristic (ROC) curve was plotted to measure the model's predictive power. According to the feature screening process, 8, 10, and 2 radiomics features and 2 clinicopathological features were finally selected to construct three prediction models (HER2-over-expression vs. others, HER2-low-expression vs. others, and HER2-zero-expression vs. others). For HER2-over-expression vs. others, the RF model outperformed other models with an AUC value of 0.843 (95%CI: 0.774-0.897), 0.785 (95%CI: 0.665-0.877), and 0.788 (95%CI: 0.708-0.868) in the training set, independent validation set, and external validation set. Concerning HER2-low-expression vs. others, the outperformance of the LR model over other models was identified with an AUC value of 0.783 (95%CI: 0.708-0.846), 0.756 (95%CI: 0.634-0.854), and 0.779 (95%CI: 0.698-0.860) in the training set, independent validation set, and external validation set. Whereas, the KNN model was confirmed as the optimal model to distinguish HER2-zero-expression from others, with an AUC value of 0.929 (95%CI: 0.890-0.958), 0.847 (95%CI: 0.764-0.910), and 0.835 (95%CI: 0.762-0.908) in the training set, independent validation set, and external validation set. Combined PET/CT radiomic models integrating with clinicopathological characteristics are non-invasively predictive of different HER2 statuses of BC patients.