Positron Emission Research Articles

Preclinical Positron Emission Tomography (PET) of Prosthetic Joint Infection Using a Nitro-Prodrug of 2-[18F]F-p-Aminobenzoic Acid ([18F]F-PABA).

Deep-seated bacterial infections are difficult to detect and diagnose due to the lack of specific clinical imaging modalities. Therefore, the bacteria-specific positron emission tomography radiotracer 2-[18F]fluoro-4-nitrobenzoic acid ([18F]FNB) was developed, which is reduced to 2-[18F]fluoro-4-aminobenzoic acid ([18F]F-PABA) by bacterial nitroreductases and has improved pharmacokinetics compared to the parent compound. PET imaging demonstrated that the uptake of 2-[18F]fluoro-4-nitrobenzoic acid in a clinically relevant Staphylococcus aureus prosthetic joint infection model was up to ∼4-fold higher in the infected joint compared to the contralateral joint. 2-[18F]Fluoro-4-nitrobenzoic acid was also able to distinguish infection from inflammation in a surgical inflammation model. Based on the mouse radiation dosimetry results, the calculated effective dose of 2-[18F]fluoro-4-nitrobenzoic acid was well below the whole-body radiation dose limit established by the Food and Drug Administration for humans. In addition, no treatment-related microscopic changes in organ histopathology were observed in a mouse acute toxicity study. Overall, these data suggest that 2-[18F]fluoro-4-nitrobenzoic acid is a specific and effective imaging agent for noninvasively diagnosing prosthetic joint infections.

Cardiorenal ketone metabolism in healthy humans assessed by 11C-acetoacetate PET: effect of D-β-hydroxybutyrate, a meal, and age

The heart and kidney have a high energy requirement, but relatively little is known about their utilization of ketones as a potential energy source. We assessed the metabolism of the ketone tracer, carbon-11 acetoacetate (11C-AcAc), by the left and right ventricles of the heart and by the kidney using positron emission tomography (PET) in n = 10 healthy adults under four experimental conditions: a 4-h fast (fasted) ± a single 12 g oral dose of D-beta-hydroxybutyrate (D-BHB), and a single complete, liquid replacement meal (hereafter referred to as the “fed” condition) ± a single 12 g oral dose of D-BHB. Under these experimental conditions, the kinetics of 11C-AcAc metabolism fitted a two-compartment model in the heart and a three-compartment model in the kidney. Plasma ketones were about 10-fold higher with the oral dose of D-BHB. During the four conditions, tracer kinetics were broadly similar in the myocardium and kidney cortex. 11C-AcAc metabolism by the kidney pelvis was similar in three of the four study conditions but, later, peaked significantly higher than that in the cortex; the exception was that the tracer uptake was significantly lower in the fed condition without D-BHB. 11C-AcAc uptake was significantly inversely correlated with age in the kidney cortex, and its oxidative metabolism was significantly positively correlated with age in the left ventricle. D-BHB blunted the insulin, gastric inhibitory peptide, and C-peptide response to the meal. This PET methodology and these acute metabolic perturbations would be suitable for future studies assessing cardiorenal ketone metabolism in conditions in which heart and kidney functions are experimentally modified or compromised by disease.

Fibroblast activation protein inhibitor PET/CT as an emerging diagnostic modality in interstitial lung disease and other fibrotic conditions.

Interstitial lung diseases (ILD) encompass a wide range of disorders characterized by alveolar inflammation and fibrotic tissue remodeling, marked by significant morbidity and mortality. Systemic sclerosis (SSc), among other connective tissue diseases, is a frequent cause of ILD. Assessment of pulmonary fibrosis is frequently constrained by the delayed manifestations of profibrotic activation of fibroblasts, which results in late macroscopic alterations detectable by standard imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) scans. 68Ga-labeled fibroblast activation protein inhibitors (68Ga-FAPI [fibroblast activation protein inhibitor]) are novel radionuclides used in the selective positron emission tomography/computed tomography (PET/CT) detection of profibrotic fibroblasts, a key player in fibrotic tissue remodeling. Application of 68Ga-FAPI in different target organs undergoing fibrosis, such as lung and heart, highlights its efficacy in detecting ongoing fibrotic processes, since FAPI tracer uptake has been correlated with clinical disease progression markers in SSc-ILD. This feature could enable physicians to detect subclinical fibrotic activity and tailor an individualised therapy plan on a case by case basis. The use of 68Ga-FAPI in ILD and other fibrotic conditions may emerge as a novel tool in future clinical practice for both activity monitoring and treatment optimisation. Other tracers tested in ILD of different etiologies have shown promising results and may in future also be considered for potential application in SSc-ILD.

Timing of Alzheimer's disease biomarker progressions: A two-decade observational study from the Alzheimer's Disease Neuroimaging Initiative (ADNI).

Alzheimer's Disease Neuroimaging Initiative (ADNI) has been pivotal in identifying and refining Alzheimer's disease (AD) biomarkers for clinical trials. This study leverages longitudinal data from participants who have progressed to amyloid-positivity during their study participation to track evolution of biomarkers and cognitive function. We modeled AD biomarker (positron emission tomography [PET], structural, cerebrospinal fluid [CSF], cognition) trajectories before and after observed amyloid-positivity onset time to detect time at which each biomarker had detectable trajectory changes. Analysis of a sub-cohort of the 20-year ADNI study (N=90) recapitulated Alzheimer's progression beginning with amyloid alterations -4.8 to -5.3 years relative to amyloid-positivity, succeeded by neurodegeneration (t=-4.0 to -4.1 years), and CSF tau (t=-0.4 to -0.5 years). Cognitive decline was observed to significantly correspond with emergence of amyloid-positivity (t=0.2 to 2.4 years). Our results corroborate temporal progression curves of AD biomarkers, providing insights on earliest detectable changes in objective and subjective cognitive function assessments.

Blood‐based biomarkers of Alzheimer's disease: Standardization and comprehensiveness

AbstractPopulation aging is sweeping across the globe, resulting in a striking prevalence of Alzheimer's disease (AD) and dementia and a heavy economic burden. Given the time window of 10–20 years from pathological initiation to clinically detected cognitive impairment, early detection can significantly impact the prevention and control of AD. The invasiveness and high cost of cerebrospinal fluid biomarkers and positron emission tomography‐computed tomography imaging limit large‐scale disease screening. However, blood‐based biomarkers (BBMs) lack these disadvantages, shedding light on their usefulness in the large‐scale identification and prevention of AD. Prominent advancement has recently been made regarding BBMs of AD co‐pathology (amyloid β, tau protein, neurofilament light polypeptide, and glial fibrillary acidic protein) to improve their accuracy as clinical diagnostics of AD to a level comparable to that of canonical methods, facilitating the large‐scale clinical implementation of diagnostic tests with higher precision. To briefly summarize, the prospects of AD BBMs rely on standardization and comprehensiveness. Calibrating the sample collection procedure and clarifying the boundaries for indices and abnormalities are beneficial for constructing a canonical diagnostic assay. The comprehensive assembly of heterogeneous clinical evidence guarantees the accuracy of diagnosis and improves the workflow for early identification.

Resolution of the Expert Council on the problem of early diagnosis of Alzheimer's disease

Alzheimer's disease (AD) is the most common neurodegenerative disease and the most common cause of dementia. In daily practice, AD is often diagnosed late, while the early stages of the disease are overlooked or mistaken for cerebrovascular pathology. However, the efficacy of existing and newly developed (disease-modifying) AD therapies is the greatest in the early stages of the disease. An accurate diagnosis of AD is possible when biological markers of the main pathological process (cerebral amyloidosis, tauopathy) are detected using positron emission tomography or neurochemical examination of cerebrospinal fluid, which are gradually being introduced into practice in Russia. The experts discussed the clinical aspects of the use of biological markers, obtained in the leading specialized centers of our country for the diagnosis and treatment of cognitive impairment (CI). First and foremost, biomarker testing is indicated in patients with mild CI and mild dementia possibly associated with AD, so that disease-modifying (pathogenetic) therapy can be initiated as early as possible upon on its availability (currently, drugs for anti-amyloid disease-modifying therapy are not registered in the Russian Federation). Patients with a non-classical (non-amnestic) or atypical AD phenotype are another group of patients in whom it is also advisable to analyze biomarkers for differential diagnostic purposes.

Acute transcutaneous auricular vagus nerve stimulation modulates presynaptic SV2A density in healthy rat brain: An invivo microPET study.

Vagus nerve stimulation (VNS) is the subject of exploration as an adjunct treatment for neurological disorders such as epilepsy, chronic migraine, pain, and depression. A non-invasive form of VNS is transcutaneous auricular VNS (taVNS). Combining animal models and positron emission tomography (PET) may lead to a better understanding of the elusive mechanisms of taVNS. We evaluated the acute effect of electrical stimulation of the left vagus nerve via the ear on brain synaptic vesicle glycoprotein 2A (SV2A) as a measure of presynaptic density and glucose metabolism in naïve rats. Female Sprague-Dawley rats were imaged with [11C]UCB-J (n = 11) or [18F]fluorodeoxyglucose ([18F]FDG) PET (n = 13) on two separate days, (1) at baseline, and (2) after acute unilateral left taVNS or sham stimulation (30 min). We calculated the regional volume of distribution (VT) for [11C]UCB-J and standard uptake values (SUV) for [18F]FDG. We observed regional reductions of [11C]UCB-J binding in response to taVNS ranging from 36% to 59%. The changes in taVNS compared to baseline were significantly larger than those induced by sham stimulation. The differences were observed bilaterally in the frontal cortex, striatum, and midbrain. The [18F]FDG PET uptake remained unchanged following acute taVNS or sham stimulation compared to baseline values. This proof-of-concept study shows for the first time that acute taVNS for 30 min can modulate invivo synaptic SV2A density in cortical and subcortical regions of healthy rats. Preclinical disease models and PET ligands of different targets can be a powerful combination to assess the therapeutic potential of taVNS.

Amyloid deposition and its association with depressive symptoms and cognitive functions in late-life depression: a longitudinal study using amyloid-β PET images and neuropsychological measurements

BackgroundAlthough depression is linked to an increased risk of dementia, the association between late-onset depression (LOD) and amyloid burden remains unclear. This study aimed to determine amyloid deposition in patients with LOD compared to healthy controls (HC) using amyloid-beta (Aβ) positron emission tomography (PET) images and neuropsychological assessments.MethodsForty patients first diagnosed with major depressive disorder after the age of 60 (LOD) and twenty-one healthy volunteers (HC) were enrolled. Depression and anxiety were evaluated using the 17-item Hamilton Depression Scale, Hamilton Anxiety Rating Scale, and Clinical Global Impression Scale. Cognitive function was assessed using the Korean versions of the Mini-Mental Status Examination, Montreal Cognitive Assessment, and Seoul Neuropsychological Screening Battery at baseline and 3-month follow-up. 18F-florbetapir PET images were co-registered with T1-weighted magnetic resonance images.ResultsThere was no significant difference in Aβ deposition between LOD and HC groups. No significant correlation between Aβ burden and depressive symptom severity was found in LOD patients. Higher somatic anxiety was correlated with lower Aβ burden in multiple brain regions, including the left inferior frontal lobe (p = 0.009), right anterior cingulate (p = 0.003), and right superior frontal lobe (p = 0.009). Despite cognitive recovery in areas such as attention (Digit Span Forward, p = 0.026), memory (Auditory Verbal Learning Test Recall Total, p = 0.010; Rey Complex Figure Test Delayed Recall, p = 0.039), and frontal executive function (Contrasting Program, p = 0.033) after three months of antidepressant treatment, cognitive improvement showed no association with amyloid deposition.ConclusionsThese findings suggest distinct mechanisms may underlie amyloid deposition in neurodegenerative changes associated with depression. While amyloid burden in specific brain regions negatively correlated with somatic anxiety, it showed no significant correlation with the severity of depression or overall cognitive function.

Positron Emission Tomography/Computed Tomography Imaging in Therapeutic Clinical Trials in Alzheimer's Disease: AnOverview of the Current State of the Artof Research.

The integration of positron emission tomography/computed tomography (PET/CT) has revolutionized the landscape of Alzheimer's disease (AD) research and therapeutic interventions. By combining structural and functional imaging, PET/CT provides a comprehensive understanding of disease pathology and response to treatment assessment. PET/CT, particularly with 2-deoxy-2-[fluorine-18]fluoro-D-glucose (18F-FDG), facilitates the visualization of glucose metabolism in the brain, enabling early diagnosis, staging, and monitoring of neurodegenerative disease progression. The advent of amyloid and tau PET imaging has further propelled the field forward, offering invaluable tools for tracking pathological hallmarks, assessing treatment response, and predicting clinical outcomes. While some therapeutic interventions targeting amyloid plaque load showed promising results with the reduction of cerebral amyloid accumulation over time, others failed to demonstrate a significant impact of anti-amyloid agents for reducing the amyloid plaques burden in AD brains. Tau PET imaging has conversely fueled the advent of disease-modifying therapeutic strategies in AD by supporting the assessment of neurofibrillary tangles of tau pathology deposition over time. Looking ahead, PET imaging holds immense promise for studying additional targets such as neuroinflammation, cholinergic deficit, and synaptic dysfunction. Advances in radiotracer development, dedicated brain PET/CT scanners, and Artificial Intelligence-powered software are poised to enhance the quality, sensitivity, and diagnostic power of molecular neuroimaging. Consequently, PET/CT remains at the forefront of AD research, offering unparalleled opportunities for unravelling the complexities of the disease and advancing therapeutic interventions, although it is not yet enough alone to allow patients' recruitment in therapeutic clinical trials.

18F-FDG-PET/CT Scan for Detection of Large Vessel Involvement in Giant Cell Arteritis: Arteser Spanish Registry.

Background/Objectives: Imaging studies have transformed the diagnosis of large vessel vasculitis (LVV) involvement in giant cell arteritis (GCA). A positron emission tomography/computed tomography (PET/CT) scan with 18-fluorodeoxyglucose (18F-FDG) has emerged as a valuable tool for assessing LVV. We aimed to determine the utility of an 18F-FDG-PET/CT scan in detecting LVV in GCA in the ARTESER registry. Methods: The ARTESER study is a large multicenter, retrospective, longitudinal, and observational study, promoted by the Spanish Society of Rheumatology. It included patients newly diagnosed with GCA across 26 tertiary hospitals from 1 June 2013 to 29 March 2019. Patients with a diagnosis of incidental GCA were included if they fulfilled specific criteria, including the ACR 1990 criteria, positive imaging examinations, or the expert clinical opinion of investigators. Differences between patients with positive and negative 18F-FDG-PET/CT scan results were analyzed using a bivariate model. A regression model assessed associations in patients with a positive scan, and the predictive capacity of the cumulative dose of glucocorticoids (GC) on PET scan outcomes was evaluated using ROC curve analysis. Results: Out of 1675 GCA patients included in the registry, 377 met the inclusion criteria of having an 18F-FDG-PET/CT scan. The majority were diagnosed with a cranial GCA phenotype, and 65% had LVV. The thoracic aorta was the most frequently affected. Cardiovascular disease, diabetes, and older age had a negative association with a positive scan outcome. The OR for having a positive 18F-FDG-PET/CTC scan was lower as the number of days increased. Depending on the cumulative dosage of the GC, the 18F-FDG-PET/CT scan showed an AUC of 0.74, with a Youden index > 60 mg/day. Conclusions: Younger patients showed a higher probability of presenting LVV as detected by the 18F-FDG-PET/CT scan. The timing of the examination and the cumulative dosage of the GC influenced the likelihood of a positive result, with earlier tests being more likely to detect inflammation.

High-resolution motion compensation for brain PET imaging using real-time electromagnetic motion tracking.

Substantial improvements in spatial resolution in brain positron emission tomography (PET) scanners have greatly reduced partial volume effect, making head movement the main source of image blur. To achieve high-resolution PET neuroimaging, precise real-time estimation of both head position and orientation is essential for accurate motion compensation. A high-resolution electromagnetic motion tracking (EMMT) system with an event-by-event motion correction is developed for PET-CTscanners. EMMT is comprised of a source, an array of sensors, and a readout electronic unit (REU). The source acts as a transmitter and emits an EM dipole field. It is placed in close proximity to the sensor array and detects changes in EM flux density due to sensor movement. The REU digitizes signals from each sensor and captures precise rotational and translational movements in real time. Tracked motion in the EMMT coordinate system is synchronized with the PET list-mode data and transformed into the scanner coordinate system by locating paired positions in both systems. The optimal rigid motion is estimated using singular value decomposition. The rigid motion and depth-of-interaction (DOI) parallax effect are corrected by event-by-event rebinning of mispositioned lines-of-response (LORs). We integrated the EMMT with our recently developed ultra-high resolution Prism-PET prototype brain scanner and a commercial Siemens Biograph mCT PET-CT scanner. We assessed the imaging performance of the Prism-PET/EMMT system using multi-frame motion of point sources and phantoms. The mCT/EMMT system was validated using a set of point sources attached to both a mannequin head and a human volunteer, for simulating multiframe and continuous motions, respectively. Additionally, a human subject for [18F]MK6240 PET imaging wasincluded. The tracking accuracy of the Prism-PET/EMMT system was quantified as a root-mean-square (RMS) error of 0.49 for 100 axial rotations, and an RMS error of 0.15 mm for 100 mm translations.The percent difference (%diff) in average full width at half maximum (FWHM) of point source between motion-corrected and static images, within a motion range of and 10 mm from the center of the scanner's field-of-view (FOV), was 3.9%. The measured recovery coefficients of the 2.5-mm diameter sphere in the activity-filled partial volume correction phantom were 23.9%, 70.8%, and 74.0% for the phantom with multi-frame motion, with motion and motion compensation, and without motion, respectively. In the mCT/EMMT system, the %diff in average FWHM of point sources between motion-corrected and static images, within a motion range of and 10 mm from the center of the FOV, was 14%. Applying motion correction to the [18F]MK6240 PET imaging reduced the motion-induced spill-in artifact in the lateral ventricle region, lowering its standardized uptake value ratio (SUVR) from 0.70 to 0.34. The proposed EMMT system is a cost-effective, high frame-rate, and none-line-of-sight alternative to infrared camera-based tracking systems and is capable of achieving high rotational and translational tracking accuracies for mitigating motion-induced blur in high-resolution brain dedicated PETscanners.

Phase 2 trial of PSMA PET CT versus planar bone scan and CT in prostate cancer patients progressing while on androgen deprivation therapy

For prostate cancer patients who experience biochemical progression during androgen deprivation therapy (ADT), prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) has not been prospectively compared to planar bone scan plus CT. This was a single-arm, head-to-head, prospective phase II trial (NCT04928820) designed to enroll 102 men with prostate cancer who experienced biochemical progression (rising prostate-specific antigen [PSA] ≥ 1 ng/mL) during ADT. All patients received 68Ga-PSMA-11 PET/CT and 99mTc-MDP planar bone scans. Each scan was interpreted by three central independent readers. The primary endpoint was the per-patient bone metastasis detection rate of PSMA PET/CT versus planar bone scan and CT. Secondary endpoints compared the number of bone metastases detected per patient and the inter-reader agreement of each imaging modality. Twenty-two men were enrolled between July 2021 and June 2022. Due to slow accrual following approval of PSMA PET radiotracers in the U.S. and a lack of a statistical signal between the two imaging modalities on interim analysis, this trial was closed early on October 2022. Median PSA was 8.5 ng/mL (interquartile range: 1.6–77.6). There was 100% agreement between the two scans. Six patients (27%) had negative findings and 16 patients (73%) had positive findings on both scans. PSMA PET/CT and bone scan plus CT detected an equal number of bone lesions for 14 patients (64%), PSMA PET/CT detected more bone lesions for six patients (27%), and bone scan plus CT detected more bone lesions for two patients (9.1%) (p = 0.092). The inter-reader agreement rates of PSMA PET/CT and bone scan plus CT were 96% and 82%, respectively (p = 0.25). In men with biochemical progression during ADT, 68Ga-PSMA-11 PET/CT and 99mTc-MDP planar bone scan plus CT had identical bone metastasis detection rates. Bone scan plus CT can continue to serve as a cost-effective and readily accessible restaging modality in patients with biochemical progression. ClinicalTrials.gov NCT04928820. Registered 16/06/2021.

Enhancing Lymphoma Diagnosis, Treatment, and Follow-Up Using 18F-FDG PET/CT Imaging: Contribution of Artificial Intelligence and Radiomics Analysis.

Lymphoma, encompassing a wide spectrum of immune system malignancies, presents significant complexities in its early detection, management, and prognosis assessment since it can mimic post-infectious/inflammatory diseases. The heterogeneous nature of lymphoma makes it challenging to definitively pinpoint valuable biomarkers for predicting tumor biology and selecting the most effective treatment strategies. Although molecular imaging modalities, such as positron emission tomography/computed tomography (PET/CT), specifically 18F-FDG PET/CT, hold significant importance in the diagnosis of lymphoma, prognostication, and assessment of treatment response, they still face significant challenges. Over the past few years, radiomics and artificial intelligence (AI) have surfaced as valuable tools for detecting subtle features within medical images that may not be easily discerned by visual assessment. The rapid expansion of AI and its application in medicine/radiomics is opening up new opportunities in the nuclear medicine field. Radiomics and AI capabilities seem to hold promise across various clinical scenarios related to lymphoma. Nevertheless, the need for more extensive prospective trials is evident to substantiate their reliability and standardize their applications. This review aims to provide a comprehensive perspective on the current literature regarding the application of AI and radiomics applied/extracted on/from 18F-FDG PET/CT in the management of lymphoma patients.

Association of Cardiovascular Risk Factors and Coronary Calcium Burden with Epicardial Adipose Tissue Volume Obtained from PET-CT Imaging in Oncological Patients.

Whole-body positron emission tomography (PET)-computed tomography (CT) imaging performed for oncological purposes may provide additional parameters such as the coronary artery calcium (CAC) and epicardial adipose tissue (EAT) volume with cost-effective prognostic information in asymptomatic people beyond traditional cardiovascular risk factors. We evaluated the feasibility of measuring the CAC score and EAT volume in cancer patients without known coronary artery disease (CAD) referred to whole-body 18F-FDG PET-CT imaging, regardless of the main clinical problem. We also investigated the potential relationships between traditional cardiovascular risk factors and CAC with EAT volume. A total of 109 oncological patients without overt CAD underwent whole-body PET-CT imaging with 18F-fluorodeoxyglucose (FDG). Unenhanced CT images were retrospectively viewed for CAC and EAT measurements on a dedicated platform. Overall, the mean EAT volume was 99 ± 49 cm3. Patients with a CAC score ≥ 1 were older than those with a CAC = 0 (p < 0.001) and the prevalence of hypertension was higher in patients with detectable CAC as compared to those without (p < 0.005). The EAT volume was higher in patients with CAC than in those without (p < 0.001). For univariable age, body mass index (BMI), hypertension, and CAC were associated with increasing EAT values (all p < 0.005). However, the correlation between the CAC score and EAT volume was weak, and in multivariable analysis only age and BMI were independently associated with increased EAT (both p < 0.001), suggesting that potential prognostic information on CAC and EAT is not redundant. This study demonstrates the feasibility of a cost-effective assessment of CAC scores and EAT volumes in oncological patients undergoing whole-body 18F-FDG PET-CT imaging, enabling staging cancer disease and atherosclerotic burden by a single test already included in the diagnostic work program, with optimization of the radiation dose and without additional costs.

Innovations in Nuclear Medicine Imaging for Reactive Oxygen Species: Applications and Radiopharmaceuticals.

Reactive oxygen species (ROS) are generated during normal cellular energy production and play a critical role in maintaining cellular function. However, excessive ROS can damage cells and tissues, contributing to the development of diseases such as cardiovascular, inflammatory, and neurodegenerative disorders. This review explores the potential of nuclear medicine imaging techniques for detecting ROS and evaluates various radiopharmaceuticals used in these applications. Radiopharmaceuticals, which are drugs labeled with radionuclides, can bind to specific biomarkers, facilitating their identification in vivo using nuclear medicine equipment, i.e., positron emission tomography and single photon emission computed tomography, for diagnostic purposes. This review includes a comprehensive search of PubMed, covering radiopharmaceuticals such as analogs of fluorescent probes and antioxidant vitamin C, and biomarkers targeting mitochondrial complex I or cystine/glutamate transporter.

Explainable AI for automated respiratory misalignment detection in PET/CT imaging.

Positron emission tomography (PET) image quality can be affected by artifacts emanating from PET, CT, or artifacts due to misalignment between PET and CT images. Automated detection of misalignment artifacts can be helpful both in data curation and in facilitating clinical workflow. This study aimed to develop an explainable machine learning approach to detect misalignment artifacts in PET/CT imaging.&#xD;Approach. This study included 1216 PET/CT images. All images were visualized and images with respiratory misalignment artifact (RMA) detected. Using previously trained models, four organs including the lungs, liver, spleen, and heart were delineated on PET and CT images separately. Data were randomly split into cross-validation (80%) and test set (20%), then two segmentations performed on PET and CT images were compared and the comparison metrics used as predictors for a random forest framework in a 10-fold scheme on cross-validation data. The trained models were tested on 20% test set data. The model's performance was calculated in terms of specificity, sensitivity, F1-Score and area under the curve (AUC). &#xD;Main Results. Sensitivity, specificity, and AUC of 0.82, 0.85, and 0.91 were achieved in ten-fold data split. F1_score, sensitivity, specificity, and AUC of 84.5 vs 82.3, 83.9 vs 83.8, 87.7 vs 83.5, and 93.2 vs 90.1 were achieved for cross-validation vs test set, respectively. The liver and lung were the most important organs selected after feature selection.&#xD;Significance. We developed an automated pipeline to segment four organs from PET and CT images separately and used the match between these segmentations to decide about the presence of misalignment artifact. This methodology may follow the same logic as a reader detecting misalignment through comparing the contours of organs on PET and CT images. The proposed method can be used to clean large datasets or integrated into a clinical scanner to indicate artifactual cases.

Medical Image Fusion for Multiple Diseases Features Enhancement

ABSTRACTThroughout the past 20 years, medical imaging has found extensive application in clinical diagnosis. Doctors may find it difficult to diagnose diseases using only one imaging modality. The main objective of multimodal medical image fusion (MMIF) is to improve both the accuracy and quality of clinical assessments by extracting structural and spectral information from source images. This study proposes a novel MMIF method to assist doctors and postoperations such as image segmentation, classification, and further surgical procedures. Initially, the intensity‐hue‐saturation (IHS) model is utilized to decompose the positron emission tomography (PET)/single photon emission computed tomography (SPECT) image, followed by a hue‐angle mapping method to discriminate high‐ and low‐activity regions in the PET images. Then, a proposed structure feature adjustment (SFA) mechanism is used as a fusion strategy for high‐ and low‐activity regions to obtain structural and anatomical details with minimum color distortion. In the second step, a new multi‐discriminator generative adversarial network (MDcGAN) approach is proposed for obtaining the final fused image. The qualitative and quantitative results demonstrate that the proposed method is superior to existing MMIF methods in preserving the structural, anatomical, and functional details of the PET/SPECT images. Through our assessment, involving visual analysis and subsequent verification using statistical metrics, it becomes evident that color changes contribute substantial visual information to the fusion of PET and MR images. The quantitative outcomes demonstrate that, in the majority of cases, the proposed algorithm consistently outperformed other methods. Yet, in a few instances, it achieved the second‐highest results. The validity of the proposed method was confirmed using diverse modalities, encompassing a total of 1012 image pairs.

The Pathophysiology and Biomarkers of Delirium.

Delirium is a major disturbance in the mental state characterized by fluctuations in arousal, deficits in attention, distorted perception, and disruptions in memory and cognitive processing. Delirium affects approximately 18% to 25% of hospital inpatients, with even higher rates observed during critical illness. To develop therapies to shorten the duration and limit the adverse effects of delirium, it is important to understand the mechanisms underlying its presentation. Neuroimaging modalities such as magnetic resonance imaging (MRI), positron emission tomography, functional MRI, and near-infrared spectroscopy point to global atrophy, white matter changes, and disruptions in cerebral blood flow, oxygenation, metabolism, and connectivity as key correlates of delirium pathogenesis. Electroencephalography demonstrates generalized slowing of normal background activity, with pathologic decreases in variability of oscillatory patterns and disruptions in functional connectivity among specific brain regions. Elevated serum biomarkers of inflammation, including interleukin-6, C-reactive protein, and S100B, suggest a role of dysregulated inflammatory processes and cellular metabolism, particularly in perioperative and sepsis-related delirium. Emerging animal models that can mimic delirium-like clinical states will reveal further insights into delirium pathophysiology. The combination of clinical and basic science methods of exploring delirium shows great promise in elucidating its underlying mechanisms and revealing potential therapeutic targets.

Synthesis of K+ channel radioligand [18F]5-methyl-3-fluoro-4-aminopyridine and PET imaging in mice.

[18F]3-fluoro-4-aminopyridine ([18F]3F4AP) is the first positron emission tomography (PET) radioligand that targets voltage-gated potassium (K+) channels in the brain for imaging demyelination. [18F]3F4AP exhibits high brain penetration, favorable kinetics for PET imaging, and high sensitivity to demyelinating lesions. However, recent studies in awake human subjects indicate lower metabolic stability than in anesthetized animals, resulting in reduced brain uptake. Therefore, there is a need for novel radioligands for K+ channels with suitable pharmacological properties and enhanced metabolic stability. Recent in vitro studies demonstrate that 5-methyl-3-fluoro-4-aminopyridine (5Me3F4AP) exhibits comparable binding affinity to K+ channels, pKa, logD, and membrane permeability as 3F4AP, and a slower enzymatic metabolic rate, suggesting its potential as a K+ channel PET tracer. In this study, we describe the radiochemical synthesis of [18F]5Me3F4AP using an isotope exchange method from the corresponding 3-fluoro-5-methyl-4-nitropyridine N-oxide, followed by a palladium on carbon mediated hydrogenation of the nitro and N-oxide groups. This method yielded [18F]5Me3F4AP with high purity and acceptable molar activity. PET/CT studies using naïve mice demonstrate that [18F]5Me3F4AP effectively crosses the blood-brain barrier and has comparable kinetics to [18F]3F4AP. These findings strongly suggest that [18F]5Me3F4AP is a promising candidate for neuroimaging applications and warrant further studies to investigate its sensitivity to lesions and in vivo metabolic stability.

Clinical development and proof of principle testing of new regenerative vascular endothelial growth factor-D therapy for refractory angina: rationale and design of the phase 2 ReGenHeart trial

BackgroundDespite tremendous therapeutic advancements, a significant proportion of coronary artery disease patients suffer from refractory angina pectoris, that is, quality-of-life-compromising angina that is non-manageable with established pharmacological and interventional treatment...